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

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

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LUNG

TRANSPLANT 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., 1960Lung Transplant: 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: 0-497-00686-3 1. Lung Transplant-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 lung transplant. 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 LUNG TRANSPLANT.................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lung Transplant ........................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 43 The National Library of Medicine: PubMed ................................................................................ 44 CHAPTER 2. NUTRITION AND LUNG TRANSPLANT ........................................................................ 93 Overview...................................................................................................................................... 93 Finding Nutrition Studies on Lung Transplant.......................................................................... 93 Federal Resources on Nutrition ................................................................................................... 96 Additional Web Resources ........................................................................................................... 97 CHAPTER 3. ALTERNATIVE MEDICINE AND LUNG TRANSPLANT ................................................. 99 Overview...................................................................................................................................... 99 National Center for Complementary and Alternative Medicine.................................................. 99 Additional Web Resources ......................................................................................................... 105 General References ..................................................................................................................... 106 CHAPTER 4. PATENTS ON LUNG TRANSPLANT ............................................................................ 107 Overview.................................................................................................................................... 107 Patent Applications on Lung Transplant .................................................................................. 107 Keeping Current ........................................................................................................................ 111 CHAPTER 5. BOOKS ON LUNG TRANSPLANT ................................................................................ 113 Overview.................................................................................................................................... 113 Book Summaries: Federal Agencies............................................................................................ 113 Chapters on Lung Transplant.................................................................................................... 114 CHAPTER 6. PERIODICALS AND NEWS ON LUNG TRANSPLANT .................................................. 115 Overview.................................................................................................................................... 115 News Services and Press Releases.............................................................................................. 115 Newsletter Articles .................................................................................................................... 118 Academic Periodicals covering Lung Transplant ...................................................................... 118 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 121 Overview.................................................................................................................................... 121 U.S. Pharmacopeia..................................................................................................................... 121 Commercial Databases ............................................................................................................... 122 Researching Orphan Drugs ....................................................................................................... 122 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 127 Overview.................................................................................................................................... 127 NIH Guidelines.......................................................................................................................... 127 NIH Databases........................................................................................................................... 129 Other Commercial Databases..................................................................................................... 131 APPENDIX B. PATIENT RESOURCES ............................................................................................... 133 Overview.................................................................................................................................... 133 Patient Guideline Sources.......................................................................................................... 133 Associations and Lung Transplant ............................................................................................ 135 Finding Associations.................................................................................................................. 136 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 139 Overview.................................................................................................................................... 139 Preparation................................................................................................................................. 139 Finding a Local Medical Library................................................................................................ 139 Medical Libraries in the U.S. and Canada ................................................................................. 139

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ONLINE GLOSSARIES................................................................................................................ 145 Online Dictionary Directories ................................................................................................... 146 LUNG TRANSPLANT DICTIONARY ...................................................................................... 147 INDEX .............................................................................................................................................. 203

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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 lung transplant 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 lung transplant, 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 lung transplant, 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 lung transplant. 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 lung transplant, 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 lung transplant. 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 LUNG TRANSPLANT Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lung transplant.

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

Tacrolimus (FK 506): A Review Source: UNOS Update. 11(3): 13-18. March 1995. Contact: Available from UNOS. 1100 Boulders Parkway, Suite 500, P.O. Box 13770, Richmond, VA 23225-8770. (804) 330-8500. Summary: In this article, the author provides readers with an update on tacrolimus (FK 506), an immunosuppressive agent approved by the FDA in 1994. Topics include the discovery and early studies of the drug; early animal transplant experiments; the use of FK506 therapy in liver transplantation, both as primary therapy and as rescue therapy; multicenter randomized liver transplantation studies; human kidney transplant studies; human heart and lung transplant studies; human small intestine transplant studies; the mechanism of action of tacrolimus; its pharmacology in humans; and the toxicity of

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tacrolimus. The author notes that tacrolimus has a unique ability to reverse ongoing graft rejection occurring under cyclosporine immunosuppression. 1 figure. 54 references.

Federally Funded Research on Lung Transplant The U.S. Government supports a variety of research studies relating to lung transplant. 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 lung transplant. 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 lung transplant. The following is typical of the type of information found when searching the CRISP database for lung transplant: •

Project Title: APPLIED GENOMICS IN CARDIOPULMONARY DISEASE Principal Investigator & Institution: Haponik, Edward F.; Professor of Internal Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: The Clinical Core will serve as the coordinating center for patient recruitment, specimen procurement and data base management. It is the mission of this Core to identify and provide disease-specific candidate genes from patients with such clinical disorders as acute lung injury, COPD, cystic fibrosis, asthma, pulmonary hypertension, pulmonary fibrosis, ischemic heart failure and both lung and cardiac transplant rejection. This core will also be responsible for the establishment of a Cardiopulmonary Tissue Repository that will maintain an archive of cryopreserved tissues and maintain an accurate data base of patient demographic and clinical data for correlation with biological end points produced by cDNA microarray. Following patient consent and registration, tissue samples and peripheral blood are delivered to the Core laboratory. The freezing facility will also serve as a repository for cyropreserved human lung and cardiac specimens. The Core Investigators will meet regularly to review all diagnostic materials on each specimen procured including histochemical stains and biopsies in order to determine a precise diagnosis and relevant demographic and clinical data for entry into the Project's data base which will include critical variables for the analysis of the biological data obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

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Project Title: APPROACHES TO THE GENETICS OF COPD Principal Investigator & Institution: Silverman, Edwin K.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 16-AUG-1999; Project End 30-JUN-2004 Summary: Cigarette smoking is the major environmental risk factor for the development of chronic obstructive pulmonary disease (COPD); however, only a subset of smokers develop clinically significant COPD. In addition to the risk from smoking, subjects with severe alpha 1-antitrypsin deficiency have a major genetic predisposition to COPD; other genetic determinants of COPD have not been proven. The frequent development of COPD in individuals with alpha 1-antitrypsin deficiency has provided a foundation for the protease-antiprotease hypothesis for the pathogenesis of COPD. However, many subjects with severe, early-onset COPD are not alpha 1-antitrypsin deficient. To define the mechanisms responsible for the development of severe, early-onset COPD unrelated to alpha 1-antitrypsin deficiency, we propose a multidisciplinary study that combines field, laboratory, and analytical approaches. We will assemble a group of 140 pedigrees ascertained through probands with severe, early-onset COPD (without severe alpha 1antitrypsin deficiency) who are referred for lung transplant or lung volume reduction surgery evaluations. We will assess these probands and their relatives with spirometry (including bronchodilator response) and a questionnaire. We will obtain genotyping with highly polymorphic short tandem repeat (STR) markers at 10 cM intervals throughout the genome from the NHLBI Mammalian Genotyping Service; these genotypes will be used to assess for genetic linkage to phenotypes including FEV1, FEV1/FVC, chronic bronchitis, and bronchodilator responsiveness. In chromosomal regions with suggestive linkage from the genome screen, additional STR markers will be tested at 1 cM intervals; multipoint linkage analysis, family-based association studies, and haplotype analysis will be used to narrow the regions likely to contain genetic determinants of COPD-related phenotypes. mRNA levels of genes within these regions narrowed by fine mapping will be compared in lung tissue from early-onset COPD probands and control subjects. The results of this study could identify specific regions of the genome which are likely to contain COPD susceptibility genes and provide candidate susceptibility genes for COPD. Identification of such genetic determinants could provide insight into the biochemical mechanisms causing the variable development of COPD at all ages, allow identification of highly susceptible individuals, and lead to new therapeutic interventions for COPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIORAD ASPERGILLOSIS

GALACTOMANNAN

EIA

FOR

DIAGNOSIS

OF

Principal Investigator & Institution: Marr, Kieren A.; Assistant Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The Bio-Rad galactomannan enzyme immunoassay (GM EIA) will soon be submitted to the FDA for approval as an aid to diagnose aspergillosis, a frequent cause of infectious death in immunosuppressed patients. Our preliminary studies suggest that the assay may also be used as a screening test to enable early diagnoses; however, the optimal cut-offs for positivity have not been determined. Defining cut-offs to optimize performance is critical for patients who have different manifestations of infection (endobronchial vs. invasive), such as in solid organ transplant recipients, and in children, who appear to have frequent false-positive results.

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The studies proposed in this project will define parameters to use the GM EIA in multiple different patient populations, using clinical samples obtained from a large ongoing FHCRC longitudinal protocol in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients, and samples obtained from multicenter trials sponsored by the NIH. Aim 1 will define parameters for use of the GM EIA as an early diagnostic test for aspergillosis in adult allogeneic HSCT patients. Studies will be performed to determine the lower limit of GM detection, identify clinical factors that impact levels of circulating GM, and to determine the role of GM EIA applied to non-blood fluids (bronchoalveolar lavage fluid and urine). Aim 2 will define appropriate cut-offs for positivity and characterize performance of the GM EIA as a diagnostic assay for aspergillosis in high-risk solid organ transplant recipients. To do this, longitudinal sample collection will be performed in a protocol conducted as a companion to an ongoing CDC-sponsored multicenter surveillance study. Aim 3 will define parameters for use of the GM EIA as an early diagnostic test for aspergillosis in neutropenic children. To determine the appropriate cut-offs for positivity in children, GM EIAs will be performed on serial sera obtained from children at high risk for aspergillosis after treatment with induction chemotherapy for AML, and after cord blood transplant. Companion protocols will be performed to collect sera as part of ongoing multicenter studies performed by the Children' s Oncology Group and the NHLBI Cord Blood Transplantation Study. Studies will be performed to determine if false-positivity of the GM EIA in children corresponds with gut translocation of GM during periods of mucositis, by measuring surrogate markers for GI integrity in a case-control study. This project is enabled by the cooperative activities of FHCRC investigators, Bio-Rad Laboratories, and several multicenter networks supported by the CDC, NIAID, and NHLBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCINEURIN INHIBITION: LUNG REPERFUSION INJURY Principal Investigator & Institution: Mulligan, Michael S.; Associate Professor of Surgery; Surgery; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Approximately 25 percent of lung transplant recipients and 15 percent of patients treated for chronic pulmonary embolic disease will develop post- operative lung ischemia reperfusion injury (IRI). Treatment is conservative and this problem continues to account for significant morbidity and mortality. Requirements for several proinflammatory mediators have been characterized. However, antagonism of a single mediator rarely produces dramatic protection. Clinical treatment with directed antibodies is likely therefore to be expensive, impractical and marginally effective. More effective interventions would block several mediators at once, potentially by acting at the transcriptional level. Inhibition of calcineurin mediated activation of NF-kB can reduce expression of a variety of proinflammatory mediators. Since cyclosporin (CSA) and tacrolimus (TAC) are calcineurin inhibitors that are already available clinically, it would be desirable to examine their effects in experimental lung IRI. CSA and TAC reduce IRI in other tissues and can consistently reduce NF-kB activation both in vitro and in vivo. In preliminary studies, we have reliably established an animal model of lung IRI and shown that NF-kB activation follows lung IRI and that activation is associated with the appearance of a number of inflammatory cytokines and chemokines. Our hypothesis, therefore, is that calcineurin mediates NF-kB activation with lung IRI which results in transcriptional upregulation of critical pro-inflammatory mediators and the ultimate development of

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tissue injury. We will address this hypothesis systematically beginning with interventional studies in vivo and proceed to mechanistic analysis both in vivo and in vitro. We will pursue three related aims: Aim 1: To determine whether calcineurin inhibition is protective against the development of lung IRI. We will accomplish this using our animal model. Aim 2: To determine whether calcineurin inhibition results in transcriptional down-regulation of mediators involved in lung IRI through an NFkBdependent mechanism. We will measure protection offered by CSA/TAC and assess associated changes in cytokine production and NFkB in nuclear protein. Aim 3: To define the cellular sources of critical mediators of lung IRI and their dependence on calcineurin driven transcription and cell-cell interactions. We will accomplish this by culturing alveolar macrophages , type II pneumocytes and pulmonary artery endothelial cells (individually and in combination) and subject them to hypoxia and reoxygenation. 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 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

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Project Title: CENTER FOR GENE THERAPY OF CYSTIC FIBROSIS Principal Investigator & Institution: Engelhardt, John F.; Associate Professor; Anatomy and Cell Biology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: Development of effective gene therapies for inherited disorders requires interdisciplinary programs which focus on disease gene identification, disease pathogenesis, and the development of technologies for gene transfer. The goal of this

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proposal is to establish a Center that will provide investigators with the opportunity to improve and/or expand their gene therapy-based research. The primary focus of this Center will be on the development of gene therapies for cystic fibrosis (CF), but will also include several other genetic diseases. Several mechanisms are proposed to meet the goals of this Center. 1) The Center will support pilot and feasibility studies directed at CF and other genetic diseases. This will bring new members and new expertise into the Center. It also provides established investigators with the opportunity to pursue novel, high risk strategies for gene therapy. 2) The Center will strengthen relevant existing Cores (Vector Core and Cell Culture Core), and develop two new Cores (Morphology Core and Animal Models Core). These Cores provide investigators with specialized vectors, primary cultures of airway epithelia, various transformed cell lines, resources, and new methods that allow them to test hypotheses that could not otherwise be evaluated. 3) The Center has formulated a Midwest Regional Consortium for the acquisition CF lung transplant tissue. This consortium will create a repository of CF and non-CF primary airway cells and tissue which are critical for the gatherings. This provides a forum for critical evaluation of research directed at the development of new approaches, model systems, and novel ideas. 5) The Center will allow expansion of gene transfer research to newly characterized genetic diseases. This will take advantage of opportunities to develop new treatments in many areas. Translation of the work to other systems will also benefit the CF research effort. 6) The Center will establish formal internal mechanisms and external consultants to review the Center, the Cores, and the pilot and feasibility projects, thereby ensuring a high level of excellence and the most appropriate utilization of the Center's resources. In summary, the Center for Gene Therapy of CF and Other Genetic Diseases will greatly strengthen existing gene therapybased research programs at the University of Iowa and will allow progression of the research in existing new directions. 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 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 fibro-obliteration of airways, and impaired lung function. In this proposal, the investigators hypothesize that the persistent expression of monocyte chemoattractant protein-1 (MCP-1) 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,

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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 timecourse 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 ischemiareperfusion 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 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

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Project Title: CHRONIC LUNG ALLOGRAFT REJECTION IN MHC-DEFINED SWINE Principal Investigator & Institution: Allan, James S.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: Graft loss from chronic rejection, which affects all solid organs to varying degrees, has become the major obstacle to the long-term success of lung transplantation. We have established a large animal model of chronic lung rejection, which reproduces with fidelity and consistency, the pathological lesions seen in human lung transplant recipients suffering from chronic rejection. Based on preliminary data and human studies, we hypothesize that chronic lung rejection is an immunologically mediated process driven by T cell recognition of major and minor histocompatibility antigens. The corollary to this hypothesis is that protocols to downregulate the immune system or to induce immune tolerance will most effectively prevent, interrupt and/or reverse chronic lung rejection. The goal of this proposal is to test this hypothesis and, in doing so, investigate the immunologic mechanisms underlying the process of chronic lung rejection. Using MHC inbred miniature swine, synthetic polymorphic allopeptides, and monoclonal antibodies cross-reactive for swine T cells, we plan to (1) define the immunogenetic requirements of chronic lung allograft rejection and characterize the cellular and humoral mechanisms that mediate this disease, (2) examine the role and mechanisms of indirect allorecognition of donor MHC peptides in the development of chronic lung rejection in miniature swine, and (3) determine the role of costimulatory molecules in the pathogenesis of chronic lung rejection in miniature swine. These studies should lead to a better understanding of the cellular and molecular mechanisms of chronic lung rejection in a clinically relevant experimental model and may ultimately lead to the development of new strategies to prevent or treat this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

Project Title: CORRELATION OF IMMUNE PARAMETERS WITH OUTCOME Principal Investigator & Institution: Reinsmoen, Nancy L.; Professor/Director; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: In most transplant programs, long-term transplant recipients tend to be treated with similar immunosuppressive protocols. However, such uniform treatment may lead to complications from over immunosuppression in some and under immunosuppression in others. Previous studies of withdrawal of one drug have not been successful. An important question is whether an individual immune parameter test or a battery of these tests would best predict long-term graft outcome in stable patients. Retrospective data from individual laboratories has suggested the immune parameters (donor antigen-specific hyporeactivity, allogeneic microchimerism, and the absence of donor antigen-specific HLA antibodies) predict successful long- term outcome after solid organ transplantation. However, each of these parameters has only been applied individuals and only to a subpopulation of transplant recipients. This grant will focus on the use of these three immunologic parameters to predict long-term graft success in a broad transplant population. We will determine whether donor antigen-specific hyporeactivity of the CD4 helped pathway (Specific Aim 1), peripheral blood allogeneic microchimerism (Specific Aim 2), and a lack of development (or regulation of) donor antigen-specific HLA antibodies (Specific Aim 3) correlate with improved long-term graft outcome. We will perform a prospective study, testing all three parameters for lung and heart recipients and the first and third parameters for kidney recipients transplant at the University of Minnesota. The transplant program at the University of Minnesota has a long-established mechanisms for clinical follow-up and clinical data collection. We will determine whether one parameter can be used in lieu of another in an organ specific manner. We plan to use these immune parameters to determine if immunosuppression can be individualized, If so, by selectively lowing immunosuppression in some recipient by maintaining it in others, we will provide significant long- term savings (cost, morbidity and outcome improvement) for solid organ transplant recipients. 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 post-

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transplant 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 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: DONOR BONE MARROW AND IMMUNOREGULATION IN LUNG TRANSPLA* Principal Investigator & Institution: Pham, Si M.; Professor; Surgery; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2004; Project Start 24-MAY-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Lung transplantation is currently the only effective treatment for end stage lung diseases. However, chronic rejection that manifests as obliterative bronehiolitis (OB) is a major cause of late death after transplantation. The incidence of OB ranges from 34% to 65% while the mortality due to OB ranges from 62% to 100%. It has been reported that a low level of bone marrow derived donor cells was present in the tissues of long-surviving recipients of solid organs. Microchimerism was associated with a decrease in OB in lung recipients. Recent clinical data show that donor bone marrow infusion augments microchimerism, and decreases the incidence of OB. The mechanism by which donor bone marrow attenuates the development of OB is unknown. Lack of such knowledge is an important problem because without it, it is unlikely that effective strategies to reduce OB and to improve the survival of lung recipients can be developed. The objective of this grant application is to determine how infusion of donor bone marrow at the time of lung transplant reduces the development of OB in lung recipients. The central hypothesis of this application is that marrowderived cells of donor origin down-regulate recipient's allo-immune response via infectious tolerance that involves T regulatory cells. We have formulated this hypothesis based on our own novel observation that bone marrow derived donor cells preferentially home to the lung graft. The rationale for the proposed research is that once we understand how recipient's immune response is modulated by donor bone

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marrow, better strategies to prevent OB can be developed. We plan to test our hypothesis by pursuing the following two specific aims. In Aim 1, we will demonstrate that donor bone marrow infusion at the time of lung transplantation modulates the recipient's alloimmune response by infectious tolerance that involves T-regulatory cells. In Aim 2 we will determine whether dendritic cells in the lung grafts, and recipient's peripheral lymphoid tissues of lung-bone marrow recipients are more tolerogeneic than those from lung-alone recipients. The proposed work is innovative, because it capitalizes on our novel findings that bone-marrow derived cells of donor origins preferentially home to the lung graft in recipients receiving donor bone marrow infusion, and that infusion of donor bone marrow reduces the incidence of obliterative bronehiolitis in humans. We expect that the results of the proposed studies will elucidate the mechanism by which microchimerism modulates the recipient's alloimmune. These results will be significant, because they may help designing therapeutic strategies to reduce OB and to prolong the survival of lung and other solid organ recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY DIAGNOSIS OF ACUTE LUNG TRANSPLANT REJECTION Principal Investigator & Institution: Tryon, Victor V.; Source Precision Medicine 2425 N 55Th St, Ste 111 Boulder, Co 80301 Timing: Fiscal Year 2003; Project Start 08-SEP-2003; Project End 07-SEP-2004 Summary: (provided by applicant): Lung transplant recipients are at high risk for acute organ rejection, especially during the first three months post-surgery. Presymptomatic diagnosis of this condition is critical for early and effective therapeutic intervention; once overt clinical symptoms indicative of transplant rejection develop, the process is usually well under way and significant lung damage may have already occurred. Standard medical practice relies heavily on serial bronchoscopies and transbronchial biopsies, two highly invasive and uncomfortable procedures which must be performed many times during the course of follow-up care. What is needed is a minimally invasive diagnostic system that can identify acute rejection in its early stages. Source Precision Medicine has performed extensive work on gene expression profiles in normals and in patients with inflammation- and immune-related diseases and has developed a system for high-precision molecular analysis that can be performed in small quantities of whole blood. The objective of Phase I is to evaluate the specific diagnostic potential of a panel of candidate gene loci. The specific aims of the proposed research are to: 1.) Measure the expression of 88 inflammation-immune related genes in whole blood from patients who are about to initiate high-dose immunosuppressive therapy for the treatment of an episode of acute LTx rejection; 2.) compare these data to reference databases of normals and to the patients, themselves, prior to the onset of rejection; and 3.) select a subset of these 88 genes coupled with candidate biomedical algorithms for use in future studies designed to test the ability to predict and monitor acute LTx using the TheraTrax system. The overall objective of this research is to develop a commercial analytical tool for early detection and evaluation of acute organ rejection in lung transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EMPHYSEMA: OUTCOMES AND TECHNOLOGY ASSESSMENT Principal Investigator & Institution: Yusen, Roger D.; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 10-JAN-2000; Project End 30-NOV-2004

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Summary: This project seeks to improve outcomes in patients with emphysema. Therapies such as lung volume reduction surgery (LVRS) and lung transplantation (LTx) offer potential improvements in quality of life, but they impose substantial risks. Thus, decision making about the use of LVRS and LTx requires trade-offs. Rational analyses of these trade-offs require valid measurements of the benefits and harms to the patients in all relevant domains that effect duration and quality of life, including morbidity, functional status, symptoms, and satisfaction. We do not have an agreed upon standard of successful therapy, specifically in situations where duration of survival is not the only issue. The instruments we use to assess procedures may not fully capture the aspects of health and quality of life that are most important. New instruments and models for assessing outcomes are necessary to complement those that exist. The specific aims of this project are 1) to further develop methods to assess outcomes of patients with emphysema, and 2) to assess the effects of lung volume reduction surgery and lung transplant on outcomes of patients with emphysema. The effects of therapies on mortality and quality of life, measured as utilities, will be assessed. Patient demographics, co-morbidity, functional status, symptoms, and satisfaction, as well as intermediate physiologic outcomes, and utilization of resources will be measured. To achieve the specific aims, primary data collection will be performed in three ways: instrument validation, cross-sectional and (pre and postoperative) longitudinal studies. Models of the relationships among functional status, satisfaction, physiology, and quality of life in patients with emphysema will be developed and used to explain the relationships among the various outcomes. We will also develop operational definitions of successful and unsuccessful treatments among patients with emphysema undergoing LVRS or LTx that account for functional status, satisfaction, physiology, and quality of life, as well as mortality. Prediction rules for outcomes among patients with emphysema undergoing LVRS or LTx will be developed. This research plan promotes the development of methods for assessing and understanding the role of new technologies and therapeutic interventions in patients with emphysema. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNDROME

FIBROPROLIFERATION

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BRONCHIOLITIS

OBLITERANS

Principal Investigator & Institution: Lama, Vibha N.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 15-AUG-2004; Project End 31-JUL-2009 Summary: (provided by applicant): Bronchiolitis Obliterans Syndrome (BOS) is the major cause of mortality after lung transplantation. Failure of immunosuppressive or anti-inflammatory therapies to meaningfully prevent or attenuate the course of the disease has focused attention on the role of fibroproliferation in its pathogenesis. Such a paradigm might involve an imbalance favoring pro-fibrotic over anti-fibrotic mediators, leading to fibroblast recruitment, proliferation and change in phenotype to more aggressive myofibroblasts with a high capacity for collagen synthesis. We have made the novel observation that fibroblasts can be cultured from the bronchoalveolar lavage fluid (BALF) of lung transplant recipients and appear to display an activated phenotype in cases with BOS. We hypothesize that the development of a pro-fibrotic milieu (increased ratio of BALF levels of pro- to anti-fibrotic mediators) and phenotypic alteration in fibroblasts are pivotal events in the clinical development of BOS. To test this hypothesis we will first study the levels of relevant pro- and anti- fibrotic biomarkers and the phenotype of fibroblasts in a cohort of patients with BOS and

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compare them to non-BOS patients (case control study, Aim 1). Second, in order to study such associations over time and the temporal sequence of events, we will serially measure these biomarkers and study phenotypic characteristics of fibroblasts longitudinally in a population of patients following lung transplant (prospective cohort study, Aim 2). This award will provide an opportunity for the Principal investigator to develop a career as a clinical researcher with expertise in translational studies in lung transplantation. A K-23 would provide the additional experience, didactic training and mentorship necessary to develop the skills necessary to transition to an independently funded investigator. An integral component of the training plan will include advanced didactic training in missing data management, longitudinal data analysis, sequential monitoring of survival endpoints and nonparametric survival analysis. These modalities of data analysis will be utilized to carry out the specific aims, thus providing practical experience to the candidate. Furthermore, the candidate will be directly mentored by one on one sessions with the co-mentors, Fernando J. Martinez MD, MS and Marc Peters-Golden MD, both of whom are well-funded researchers with a long track record of mentoring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION MICROARRAYS IN LUNG REJECTION Principal Investigator & Institution: Hertz, Marshall I.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: (provided by applicant): The overall goal of Project 3 is to identify gene expression patterns associated with lung transplant rejection using a new laboratory approach: large scale gene expression microarray (>10,000 genes) technology. We are uniquely positioned to accomplish this by virtue of our active clinical lung transplant program, comprehensive Lung Transplant Database, and the advanced facilities and expertise of the University of Minnesota Biomedical Genomics Center. Acute rejection is common after lung transplantation, occurring in up to 50 per cent of recipients during the first post transplant year. Although it is almost never immediately life threatening, acute rejection is a major risk factor for the later development of chronic lung rejection, or OB, the most important threat to the long-term survival of lung transplant recipients. The statistical relationship between acute and CR exists despite the fact that, in most cases, the histologic findings of acute rejection resolve after treatment. Based on this observation, a fundamental assumption of the proposed research is that specific genes are activated during acute rejection, some of which remain persistently activated despite treatment, and contribute to the pathogenesis of OB. Thus, identification of these genes may serve to identify recipients at risk for CR. In this proposal we will complete two necessary steps toward this goal: 1) identification of specific patterns of gene expression in BAL cells and peripheral blood mononuclear cells that differentiate patients with and without acute lung rejection histology; and 2) identification of genes that are reliably and persistently expressed after treatment induced normalization of acute rejection histology. If successful, these studies will set the stage for additional studies to determine the predictive value of persistently expressed acute rejection associated genes for the subsequent development of CR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE MECHANISMS OF REJECTION IN HUMAN LUNG ALLOGRAFTS Principal Investigator & Institution: Mohanakumar, Thalachallour; Professor; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 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

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Project Title: IMMUNE RESPONSES IN LUNG ALLOGRAFT REJECTION Principal Investigator & Institution: Wilkes, David S.; Calvin H. English Professor of Medicine; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167

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Timing: Fiscal Year 2002; Project Start 15-MAR-1999; Project End 14-MAY-2003 Summary: Lung allograft is believed to be initiated between donor lung macrophages and dendritic cells leading to presentation of major histocompatibility complex (MHC) antigens that stimulate host lymphocytes. Direct or indirect allo-recognition of donor MHC antigens or proteins homologous to MHC antigens (MHC-"like") is believed to perpetuate the rejection process. Conversely, indirect allo-recognition of MHC or MHC"like" peptides in the pre-transplant period may prevent rejection activity. Although donor MHC antigens are usually the target of allo-immune responses. alpha-chains of type V and XI collagen, that may be homologous to MHC proteins, are also recognized as antigens during lung allograft rejection. Therefore, pre-transplant immunization with peptides of type V or VI collagen may modulate the rejection response. We have developed a murine model in which the instillation of allogeneic (C57BL/6,H-2,1-a/b) bronchoalveolar lavage cells (96% macrophages, 1-2% dendritic cells) into the lungs of recipient mice (BALB/c, H-2/d, 1-a/d) reproduce the histology and cellular and humoral immunology of acute lung allograft rejection observed in humans, as well as, immune responses to type V and XI collagen. Utilizing this unique model the current proposal tests the hypothesis that allogeneic lung macrophages and dendritic cells mediate lung allograft rejection, and examines the molecular mechanisms responsible for the rejection process by examining the following specific aims: Aim 1. To determine the interactions between donor lung macrophages and dendritic cells and the microenvironment of the lung that lead to up-regulated allo-immune responses in the allograft, soluble signals produced locally in response to the instillation of allogenic macrophages and dendritic cells in recipient lungs will be examined for their role in facilitating rejection. 2. To determine the role of direct and indirect allo- recognition in the pathogenesis of lung allograft rejection, the requirement for functional donor accessory cells or recipient accessory cells in graft destruction will be tested. Aim 3. To determine the role of MHC alloantigens, and CD4+ and CD8+ lymphocytes in the rejection process, lung accessory cells which do not express MHC II or MHC I or both antigens will be instilled into the lungs of recipient mice followed by an assessment of the cellular and humoral immune changes and histology in recipient lungs. Aim 4. To determine if indirect allo- recognition of peptides that may be homologous to MHC antigens prior to transplantation down regulates the rejection response, BALB/c mice will be immunized with peptides of type V and XI collagen prior to instilling C57BL/6 bronchoalveolar lavage cells into BALB/c mice followed by an assessment of the histology, and immunology of acute rejection. The goal of these studies is to discern the immune mechanisms of lung allograft rejection at a molecular level so targets may be identified for therapeutic intervention to prolong the survival of lung allograft recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOBIOLOGY OF TRANSPLANT OBLITERATIVE AIRWAYS DISEASE Principal Investigator & Institution: Mueller, Daniel L.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: (provided by applicant): Lung allotransplantation frequently fails due to the late development of OAD as a consequence of chronic immune graft rejection. Such failures continue to occur, in part, because our current understanding of the immunobiology responsible for the onset of the airway fibrosis is quite limited. Using heterotopic tracheal allotransplantation in mice, we have determined that directly

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alloreactive CD8 T cells as well as self-MHC-restricted CD4 T cells responding against minor transplantation antigens cooperate in the induction of OAD. We now propose to take advantage of Tg mouse technology to investigate this pathological CD8 and CD4 T cell response against tracheal allografts. Using this technique, tracheal allograft reactive TCR Tg T cells can be tracked and lymphokine and activation molecule expression and function in these T cells can be determined during the development of OAD. Therefore, we specifically aim to: 1) Investigate the nature of the cooperativity that exists between direct class I alloreactive CD8 and minor antigen reactive CD4 T cells in the induction of OAD following airway allotransplantation, 2) examine the role of costimulatory signal depend T cell lymphokines and effector molecules in the development of OAD in tracheal allografts, and 3) test the capacity of clonal energy induction in alloreactive CD8 and CD4 T cells to inhibit the development of OAD following tracheal allograft transplantation. The further development and validation of this Tg mouse model system will provide the transplantation field with a tool that more accurately assesses the activities of those T cells responsible for promoting chronic lung allograft injury. In addition, the information obtained in these experiments should serve as important pre clinical data for the development of effective immunomodulatory approaches to the problem of alloantigen specific transplantation tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOPATHOGENESIS OF CHRONIC ALLOGRAFT REJECTION Principal Investigator & Institution: Sayegh, Mohamed H.; Director, Transplantaion Research Center; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 19-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The most common cause of late Allograft failure, excluding death with a functioning graft in the case of kidney transplantation, is a clinicopathologic entity termed chronic rejection. Chronic rejection is common to all solid organ transplants, including kidney, heart, lung, pancreas and to a lesser extent, liver. Despite extensive research, the precise mechanisms responsible for the characteristic pathological and functional changes seen in chronic rejection remain unclear. The overall hypothesis of this Program Project is that the alloimmune response, and especially CD4+ T cell recognition of donor MHC peptides presented by self antigen-presenting cells (indirect allorecognition), is a central and key event that is responsible for the initiation and progression of chronic rejection. In addition, based on studies in small animals, alloantigen-independent mechanisms contribute to this process by promoting immune recognition and injury to the graft. Therefore, our goal is to study the contribution and mechanisms of the alloimmune response, along with interactions with key alloantigen-independent factors in the pathogenesis of chronic rejection in humans. In Project 1, Dr. Madsen and co-investigators will focus on studying the immunopathogenesis of chronic rejection using clinically relevant large animal (miniature swine) models of heart and lung transplantation. These models are unique in that they are the only large animal models with defined MHC systems and reproducible chronic rejection pathology. A major focus of Project 1 is to study immune responses to CMV and autoantigens in humans with chronic allograft rejection, as an extension of the studies in the miniature swine. In Project 2, Dr. Briscoe and colleagues plan to study the mechanisms of the interactions between donor endothelial cells and recipient antigen-presenting cells and T cells in promoting indirect alloimmune responses and chronic rejection. In Project 3, Dr. Sayegh's group will investigate the immunopathogenesis of chronic rejection with emphasis on the indirect alloimmune T cell and antibody response, and interactions with alloantigen-independent mechanisms

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in human renal transplant recipients. In the Scientific Core, Dr. Hancock will provide the infrastructure and technology to perform morphology, immunopathology and molecular analyses of tissue and peripheral blood mononuclear cells provided by the 3 Projects. Dr. Sayegh, along with Dr. Patricia Hibberd, Director of the Clinical Research Core Programs Office at Children's Hospital, will lead the Administrative and Data Management Core which will coordinate all administrative, statistical and data management issues of the Program Project. It is the collective results from our human studies in transplant recipients, our in vitro mechanistic experiments, and our large animal model that will provide a better understanding of the pathogenesis of chronic rejection. Our studies will yield clinically relevant information that will result in development of better assays to monitor and predict patients at risk for development of chronic rejection, as well as development of new therapeutic strategies to prevent this process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNORECOGNITION IN CHRONIC ALLOGRAFT REJECTION Principal Investigator & Institution: Madsen, Joren C.; Associate Professor of Surgery; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002 Summary: (provided by applicant): Using an immunologically versatile herd of MHC inbred miniature swine, we have developed and validated the only large animal model of heart and lung transplantation in which vascular and bronchial lesions reproduce with fidelity and consistency those lesions seen in human heart and lung transplant recipients suffering from chronic rejection. The current proposal is designed to elucidate the cellular and molecular mechanisms underlying the pathogenesis of chronic rejection in this clinically relevant large animal model and then to corroborate these finding in human heart transplant recipients. Our hypotheses, based on emerging rodent and human studies, are 1) that chronic rejection is mediated by an immune process initiated by CD4+ T cells that recognize donor allopeptides via the indirect pathway of allorecognition, 2) that recognition of non l MHC peptides derived from either viral antigens (e.g., CMV) or self proteins (e.g., cardiac myosin) can interact with the immune response to MHC peptides, and 3) that these immune responses can ignite, amplify or recruit one another, thus augmenting the chronic rejection response. To establish whether chronic rejection in large animals and humans is the end-result of the immune recognition of allopeptides, and to determine if the recognition of non-MHC peptides contribute to this process, we will use synthetic MHC allopeptides, MHC-linked viral tetramer analyses, and cardiac myosin to interrogate indirect alloimmununity, anti-viral immunity, and organ-specific autoimmunity, respectively. We plan to 1) examine and compare the roles of MHC allopeptides and organ-specific autoimmunity to cardiac myosin and antiviral immunity in the pathogenesis of CHR in miniature swine, 2) examine and compare the roles of MHC allopeptides and anti-viral immunity in the development of CLR in miniature swine, and 3) determine the role of autoimmune responses to cardiac myosin and anti-viral immunity to CMV in development of chronic rejection in human heart recipients. These mechanistic studies are critical to the development of successful therapeutic strategies aimed at extinguishing the chronic rejection response at its inception. A strategy of early intervention (at the immune recognition phase) would have the best chance of avoiding the programmed sequela of tissue injury and inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPACT TRANSPLANTATION

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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 •

Project Title: IMPACT OF MIND-BODY INTERVENTIONS POST ORGAN TRANSPLANT Principal Investigator & Institution: Gross, Cynthia R.; Professor; Experimental College; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-APR-2008 Summary: (provided by applicant): Solid organ transplant recipients require life-long immunosuppressive therapy that leads to side effects, complications and chronic symptoms, and reduces health-related quality of life. Pharmacologic options for managing symptoms increase the risks of side effects and drug interactions, and may

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reduce adherence by complicating an already challenging medication regimen. In contrast, mind-body based complementary therapies, such as mindfulness-based stress reduction (MBSR), may be ideal to treat distressing symptoms and negative emotions after transplantation. Our long-range objective is to develop evidence-based recommendations for non-pharmacologic strategies that provide symptom relief to transplant recipients, and are safe, practical and cost-effective. The specific aims are to: 1) Test the effectiveness of a MBSR program on symptom management (as measured by well-validated, self-report scales for symptoms of depression, anxiety and sleep disturbance), objective sleep changes, health-related quality of life and overall quality of life in transplant recipients at 6- and 12-mos follow-up; and 2) Evaluate the impact of this MBSR program on health care utilization and costs at 6- and 12-mos follow-up. We will randomize patients (N=150) to: 1) a MBSR intervention arm (8 wks of group instruction in mindfulness meditation techniques followed by home practice combined with individualized telephone monitoring); or 2) a health education (HE) active control arm, delivered in a format to match MBSR for instructor attention and group support. The sample will consist of kidney, kidney/pancreas, pancreas, lung, liver, heart or heart-lung transplant recipients at least 6-mo after transplant surgery. A two-stage randomization scheme will form a temporary, Delayed-Intervention (DI) inactive control arm for internal validation. The DI group will be randomized to MBSR or HE after 26 weeks of observation. This is a low cost, low risk intervention that, if successful, could be replicated easily, and result in important reductions in health care costs while improving the well being of patients with organ transplants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

22

Lung Transplant

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: IP-10 CHEMOKINE: ROLE IN T CELL RECRUITMENT AND DISEASE Principal Investigator & Institution: Luster, Andrew D.; Chief, Director, and Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 01-MAR-1996; Project End 31-DEC-2008 Summary: (provided by applicant): The attraction of leukocytes to sites of inflammation and infection is an essential component of the host response to disease. This process is controlled by chemokines, which are chemotactic cytokines. IP-10 (CXCL 10) is a chemokine that specifically attracts effector T cells and "innate lymphocytes" by activating a seven transmembrane spanning G protein-coupled chemokine receptor, CXCR3, which is expressed on these cells. Chemokines also have activities on nonhematopoietic cells and may be important mediators that link inflammation to tissue repair processes. In this regard, IP-10 inhibits angiogenesis and fibrosis in vivo. The molecular mechanism of these later effects have not been clearly established. IP-10, like many other chemokines, is a basic protein that binds to proteoglycans and also has the ability to form higher order aggregates. The functional consequences of these interactions are not clear, although they likely play important roles in IP-10's biological activity in vivo, especially in cells such as endothelial cells and fibroblasts where CXCR3 expression has been difficult to demonstrate. In this renewal application, we propose to continue our studies on IP-10 to define the structural domains that mediate its biological activities in vivo, to determine the mechanisms that control the differential regulation and function of the three CXCR3 ligands -- IP-10, MIG and I-TAC -- in vivo, and to define the role of CXCR3 and its ligands in the trafficking of defined subsets of antigenspecific CD4 and CD8 cells in vivo. Specifically, we propose: (1) To determine the structural domains of IP-10 that mediate its binding to CXCR3 and proteoglycans and its tendency to oligomerize, and the biological consequences each of these interactions have for IP-10's ability to induce T cell recruitment and inhibit angiogenesis and fibrosis in vivo; (2) To determine the unique roles of IP-10 and MIG in allograft rejection in a model of lung transplantation, and to determine the cellular and molecular mechanisms regulating the differential expression of these two CXCR3 ligands in this model; (3) To determine the role of IP-10, MIG, I-TAC and CXCR3 in the generation and trafficking of defined subsets of antigen-specific of CD4 and CD8 T cells in vivo. Studies supported by this grant have contributed to our understanding of IP- 10 and have helped establish IP10 and CXCR3 as attractive candidates for modulating the immune response in clinically relevant diseases, such as solid organ transplantation, pulmonary fibrosis and cancer. The current proposal will extend and refine our knowledge of this important clinically relevant chemokine-chemokine receptor system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISCHEMIC TRANSPLANT

INJURY

IN

CADAVER

DONORS

FOR

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LUNG

Principal Investigator & Institution: Egan, Thomas M.; Associate Professor of Surgery; Surgery; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 20-SEP-2001; Project End 31-JUL-2004 Summary: Clinical lung transplantation (LTX) is severely limited by a shortage of suitable donors. Thus, hundreds of Americans die annually waiting for LTX, and thousands more with end stage respiratory disease are denied the opportunity of improved health that LTX may afford them. The lung is unique among solid organs in that it does not rely on perfusion for cellular respiration. We hypothesize that lung tissue remains viable for hours after circulatory arrest and death, and thus the lung may be suitable for transplantation, even if retrieved at substantial intervals after circulatory arrest and death of a non-heart beating organ donor (NHBD). We have substantiated this hypothesis with animal LTX experiments, which demonstrate that lungs retrieved at intervals after circulatory arrest may function well, but are affected adversely by ischemia-reperfusion injury (IRI). There is evidence that the cyclic nucleotide cAMP and cGMP are important mediators of altered endothelial permeability in lung IRI. IRI is associated with upregulation of endothelial cellular adhesion molecules (CAM) which recruit polymorphonuclear leukocytes (PMN) to the lung that contribute to IRI. We hypothesize that cyclic nucleotides play a pivotal role in maintaining endothelial cytoskeletal integrity, which in turn plays a role in CAM upregulation. This proposal aims to: 1) Characterize events that occur in the NHBD lung during the period of normothermic ischemia after circulatory arrest but prior to reperfusion. 2) Determine the relationship between CAMP and cGMP in lung tissue and pulmonary endothelial permeability changes due to IRI after circulatory arrest. 3) Determine the relationship between CAM expression, PMN recruitment, and lung function in transplanted lungs from NHBDs. Utilizing a rat isolated lung perfusion model and a rat LTX model, this proposal intends to achieve a better understanding of the molecular events involved in IRI and develop strategies that minimize lung injury in the setting of retrieval from NHBDs. This will facilitate the introduction of lung retrieval for transplant from NHBDs, which has the potential to extend the lives of thousands of Americans suffering with a variety of lung diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: KIDNEY TRANSPLANT CARELINK Principal Investigator & Institution: Safran, Charles; Chief Executive Officer; Clinician Support Technology, Inc. Suite 201 Newton, Ma 02459 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2003 Summary: (provided by applicant): We propose Kidney Transplant CareLink, an Internet-based learning, communication, and care support application that will help kidney transplant recipients improve their self-management skills and their ability to maintain immunosuppressive regimens over time using learning and intervention strategies, including individualized teaching, reminders, interactive counseling, monitoring, and peer support and mentoring. We will use information gathered by patient self-report to tailor learning and communication interventions to patients? individual needs. Kidney Transplant CareLink will be a patient-centered Internet web site connecting patients directly to their own transplant center care team. It will be a "one-stop," 24/7 source of knowledge, individualized learning and care support, self-

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Lung Transplant

care functionality, and emotional support. Transplant recipients will get information they want, when they want it, and in a format they prefer, directly from their own transplant center providers. It will enable recipients and the transplant center care team to sustain a strong sense of connection, knowledge exchange, and collaboration over time, regardless of geography. Kidney Transplant CareLink will be used by kidney transplant centers and their patients, as well as health plans and payers. If successful, this Internet-based model will be applicable to large and growing populations of pancreas, liver, heart, and lung transplant recipients. PROPOSED COMMERCIAL APPLICATION: We believe that Kidney Transplant CareLink will effectively address significant problems that adversely affect patient outcomes in kidney transplantation. We believe there is currently no commercial application available to transplant centers and patients that addresses the range and specificity of needs and that has the potential to improve outcomes as our model does. Kidney Transplant CareLink addresses a significant unmet need in the marketplace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS CAUSING PULMONARY XENOGRAFT INJURY Principal Investigator & Institution: Davis, R Duane.; Associate Professor; Surgery; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2005 Summary: Although primary transplantation has evolved into an effective therapy for end-stage lung disease, the balance between organ supply and demand greatly limits its applicability. Pulmonary xenotransplantation using swine lungs in humans could provide a solution to this problem. However, pulmonary xenografts are rapidly reflected by mechanisms distinct from those causing hyperacute rejection of the heart or kidney. The long-term objective of this project is to determine the mechanisms responsible for pulmonary xenograft injury, develop strategies which will prevent this injury and to enable the clinical application of pulmonary xenotransplantation. Although the mechanisms responsible for rejection of the cardiac xenograft are dependent upon the binding of xenoreactive antibody to the Gal(1-3)Ga1 epitope with subsequent complement activation, the importance of this interaction in lung xenografts is unclear. The aims of this proposal are as follows: (1) define the role of the pulmonary intravascular macrophage and other resident macrophage and other resident macrophages within the lung in inducing pulmonary vasoconstriction, endothelial cell activation and initiation of coagulation; (2) to define the role of classical complement pathway activation, particularly anaphylatoxins and xenoreactive antibody in pulmonary xenograft injury; and (3) characterize the role of tissue factor initiated coagulation and inadequate regulation of coagulation in pulmonary xenograft injury particularly with regards to endothelial cell activation and augmentation of inflammation. The experiments outlined in this proposal will (1) deplete resident macrophages, both the intravascular and alveolar macrophages; (2) use of anti-C5a monoclonal antibodies and other inhibitors of the complement system; (3) depletion of Gal antibody and to use lungs of the Gal epitope; and (4) blockers of tissue factor dependent coagulation, swine vWF platelet interaction and regulator of the coagulation system that are effective in a swine to primate model. It is anticipated that these studies will further delineate the mechanisms responsible for the early pulmonary xenograft injury and to begin to allow for examination of the mechanisms responsible for acute vascular rejection. Strategies developed from these studies should form the basis for the application of pulmonary xenotransplantation to the treatment of patients with pulmonary failure.

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

Project Title: MECHANISMS GOVERNING HYPERACUTE REJECTION OF THE LUNG Principal Investigator & Institution: Pierson, Richard N.; Associate Professor of Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS ALLOGRAFTS

OF

MAST

CELL

APOPTOSIS

IN

LUNG

Principal Investigator & Institution: Fang, Kenneth C.; Cardiovascular Research Inst; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 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 metalloproteinasedependent 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 metalloproteinasedependent 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

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Project Title: MECHANISMS OF PULMONARY ALLOGRAFT REJECTION IN SWINE Principal Investigator & Institution: Johnston, Douglas R.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-FEB-2002 Summary: Using miniature swine inbred to homozygosity at the MHC loci, we have developed a large animal model of chronic lung allograft rejection that reproduces with fidelity those histologic lesions seen in patients suffering from chronic lung rejection. The current proposal is designed to elucidate the mechanisms of chronic lung allograft rejection in these swine, with particular attention to the role of indirect recognition of donor MHC peptides. We hypothesize that chronic lung rejection is an immunological process mediated by T cell recognition of alloantigens, and that indirect recognition of donor allopeptides may play a dominant role in this process. A recent clinical study demonstrated that allorecognition of HLA class I-derived peptides correlated with the development of chronic rejection in human lung transplant recipients. However, definitive experimental evidence linking indirect allorecognition and chronic rejection in the development of chronic lung rejection using synthetic class I MHC allopeptides Specifically, we will define which MHC peptides are recognized during chronic lung rejection and whether priming animals with immunogenic class I MHC peptides will induce or accelerate chronic lung rejection. Then, we will attempt to induce tolerance to the indirect pathway in lung transplant recipients using T cell co-stimulatory blockade combined with donor allopeptides. Our hypothesis would predict that this clinically relevant therapeutic strategy would prevent the development of chronic rejection. These preclinical studies will contribute substantially to our knowledge of the mechanisms and treatment of chronic lung rejection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDIATORS OF FIBROSIS IN SCLERODERMA SKIN AND LUNG Principal Investigator & Institution: Feghali, Carol A.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology that affects mostly women and is associated with significant morbidity and mortality. No effective therapies or cures for SSc are yet available. One of the hallmarks of SSc is overproduction of extracellular matrix components such as collagen and fibronectin by fibroblasts in the skin and internal organs. We have made the novel observation of a 20-fold increase in the expression of insulin-like growth factor binding protein 5 (IGFBP-5) in fibroblasts from the clinically affected skin of SSc patients. IGFBP-5, as well as IGFBP-3, are produced by fibroblasts and modulate the actions of IGF-I, including fibroblast activation and overproduction of collagen. We hypothesize that the IGFBP/IGF-I axis contributes to the development and perpetuation of skin and lung fibrosis in SSc. Our studies will use two unique sample sets available to us--fibroblasts and tissues from monozygotic (MZ) and dizygotic (DZ) twins discordant for SSc and from lungs of SSc patients undergoing lung transplant surgery and unused donor lungs-and target two organs affected by SSc--skin and lung. These samples constitute a unique and valuable resource. Our aims are l) to determine the regulation of IGFBP-3 and IGFBP-5 in vitro and in vivo in skin an lung tissues of SSc patients and twin and non-twin controls; 2) to determine the function of IGFBPs on skin and lung fibroblasts and identify key molecules downstream of IGFBPs; 3) to determine the

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mechanism of IGFBP-mediated effects on fibroblasts, including whether the effect of IGFBPs is IGF-I-dependent or - independent, the identification of IGFBP binding partners, and the effect of suppressing IGFBP expression on the fibrotic phenotype. Our combined approach using lung and skin fibroblasts and tissues will allow us to identify the systemic mechanisms that underlie the skin and lung phenotype in SSc, while the use of samples from twins discordant for SSc will allow us to determine the importance of the inherited genetic background in the development of the 'scleroderma' phenotype. Our results will provide important insights into mechanisms of overproduction of extracellular matrix components by fibroblasts and thus the pathogenesis of fibrosis. Identifying key steps in the cascade of events culminating in fibrosis will facilitate the development of novel targeted therapies for scleroderma and for other fibrotic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROCHANNEL ASSEMBLIES FOR ARTIFICIAL LUNGS Principal Investigator & Institution: Mockros, Lyle F.; Biomedical Engineering; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2004; Project Start 06-FEB-2004; Project End 31-JAN-2007 Summary: (provided by applicant): The objective of the proposed research is to develop technology for producing prosthetic assemblies of microchannels that can be utilized in artificial organs. These microchannels, with diameters of 10 to 20 microns, are imbedded in a matrix material with nanoscale pores. The microchannel assemblies somewhat simulate physiologic capillary beds. Mass transfer to/from blood flowing in such assemblies will be greatly enhanced compared to that with current technology. Although possibly applicable to a variety of organ-function replacement devices, the overall specific aim of the current proposal is to develop the technology for artificial lungs. Effective artificial lungs could have a significant clinical impact as a bridge to lung transplantation, as a support device immediately post lung transplant, and as a rescue and/or supplement to mechanical ventilation during treatment of severe respiratory failure. Preliminary calculations suggest that a 250 ml volume artificial lung using 12 mu m microchannel wafers for gas exchange could process 4 I/min blood using air. The basic component of these microchannel assemblies for artificial lungs will be wafers of porous, biocompatible matrix containing microchannels. We propose to produce sample wafers of this basic component and conduct a series of gas transfer studies to determine the dependence of transport efficiency on blood flow rate, gas-side oxygen concentration, microchannel diameter and length, and wafer matrix material. We also propose to investigate methods to improve the production of these wafers using different fiber and matrix materials and by varying the preparation procedure. Our proposed technique involves (1) making an array of closely spaced fibers as template for the microchannels, (2) imbedding the fiber bundle in a porous matrix, (3) removing the fibers, thereby creating an array of microchannels within the porous matrix wafer, (4) machining the wafer to a desired shape, (5) coating the external faces with a thin but dense nonporous film, and (6) coating the microchannel walls and wafer surfaces with silicone rubber for biocompatibility. We have successfully demonstrated steps (1) to (3), and produced small samples of 12 mu m diameter channels in a wafer. The results of the proposed study will provide proof of concept that such microchannel devices are substantially superior to the conventional devices. Future work would include detailed blood compatibility tests and address scale-up issues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION TRANSPLANTATION

OF

INNATE

IMMUNITY

IN

LUNG

Principal Investigator & Institution: Matalon, Sadis; Acting Associate Provost for Research; Anesthesiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): A multi-center clinical trial sponsored by Fujisawa Healthcare, Inc, was planned to compare the efficacy of treating lung transplant patients with tacrolimus and sirolimus versus tacrolimus and azathioprine in reducing the incidence of acute rejection during the first twelve months after lung transplantation. Infection is a secondary endpoint and is assessed throughout the trial (i.e. for 3 years after randomization). Presently the mechanisms by which these agents may modify lung innate immunity have not been identified. Herein, we are proposing to isolate SP-A and AMs from the bronchoalveolar lavage fluid (BALF) of patients participating in this clinical trial to identify differences in the ability of AMs to kill gram positive and gram-negative bacterial pathogens and to identify differences in quantity of SP-A and modifications thereof. These data will be correlated with incidences of infection and rejection in patients participating in the clinical trial. We are also proposing to identify basic mechanisms by which normal but not nitrated SP-A enhances phagocytosis. These goals will be accomplished by completing the set of measurements outlined in the following specific aims: (1) Measure levels of surfactant lipids and SP-A in bronchoalveolar lavage (BAL) samples from patients treated with tacrolimus and sirolimus vs. tacrolimus and azathioprine. Oxidative modification to SPA (oxidation and nitration) will be assessed by Western blotting, ELISA and mass spectrometry analysis using techniques already established in our laboratory; (2) Quantitate levels of inflammatory cytokines (TNFa, INFgamma, IL-6 and IL-lb), as well as levels of nitrate and nitrite, the stable end products of NO metabolism, and nitrotyrosine in the BAL of these patients; (3) Assess the extent of pathogen killing (Klebsiella pneumoniae, a gram negative bacterium and Staphylococcus aureus, a gram positive bacterium) by AMs isolated from the lungs of these patients in the presence of SP-A and surfactant lipids, and (4) Identify putative mechanisms responsible for decreased ability of oxidized or nitrated SP-A to mediate pathogen killing by AMs. We propose that SP-A binding to AM receptors leads to activation of phospholipase C (PLC) which releases 1,4,5 inositol triphosphate (IP3) resulting in Ca+2 release from the endoplasmic reticulum. SP-A nitration may lead to decreased binding, diminishing or abrogating intracellular Ca+2 changes. Our data may provide mechanistic insight into why some patients may develop clinical infection and acute and chronic rejection and thereby form the rationale basis for choosing between these two immunosuppressive regiments for the management of patients with lung transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMR IMAGING OF INERT FLUORINATED GASES IN LUNGS Principal Investigator & Institution: Kuethe, Dean O.; Scientist; New Mexico Resonance 2301 Yale Blvd Se, Ste C1 Albuquerque, Nm 87106 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 31-JUL-2005 Summary: (provided by applicant): This project endeavors to provide safe non-invasive, but powerful imaging methods for studying pulmonary physiology and diagnosing and evaluating lung diseases. One aim is to develop a new method of imaging alveolar ventilation to blood perfusion ratios (VA/Qs). The spatial distribution of this ratio is of

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central diagnostic importance in obstructive lung disease and characterizes the lung's ability to exchange gas. An advantage of our new method over our prior one is that patients who regularly breath oxygen enriched air will not have to breath gas with normal oxygen concentrations, but can breath a mixture rich in oxygen the entire time. The method will be developed in laboratory rats. Specifically, it involves imaging the longitudinal nuclear magnetic relaxation time of an inert fluorinated gas, which we recently discovered is a monotonic function of VA/Q. Because it will quantify VA/Qs in the low range that cause poor arterial blood gases, it is not only potentially a diagnostic tool but also a tool for advancing the physiology of gas exchange in diseased and normal individuals. After development, both VA/Q imaging methods will be applied to a study of elastase induced emphysema in rats. A second aim is to systematically develop methods to detect magnetic particles in images of inert fluorinated gas. The methods will be applied to collaborative studies of the patterns of deposition of magnetically labeled aerosol particles in rat lungs and the invasion of transplanted rat lungs by magnetically labeled immune cells. Understanding of how and where aerosol particles deposit in lungs is important to advancing the toxicology of inhaled air pollution and can further the effectiveness of inhaled drugs. Imaging lung rejection is important to diagnosing acute rejection and studying the rejection process to develop improved immunosuppressive strategies. Specifically, we will tailor methods of detecting magnetic particles in gas images for use in our collaborator's animal models and laboratories by systematic exploitation of the frequency shift and diffusional signal loss contrast mechanisms. With this second aim, we will advance inert fluorinated gas imaging beyond a development and demonstration stage to a new research tool that provides previously unavailable data to medical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PAL: PRE-CLINICAL FABRICATION & OUTCOMES STUDIES Principal Investigator & Institution: Zwischenberger, Joseph B.; Professor; Mc3, Inc. 3550 W Liberty Rd, Ste 3 Ann Arbor, Mi 48103 Timing: Fiscal Year 2003; Project Start 01-MAY-2001; Project End 30-JUN-2005 Summary: (provided by applicant): End-stage Lung Disease from all causes is the fourth leading cause of death in the US. Despite the success of lung transplantation, demand for donor lungs has steadily outgrown supply. Currently, the average wait is 2 years, with 30% wait-list mortality. Likewise, acute respiratory distress syndrome (ARDS) is a predominant cause of death in trauma and critically ill patients. A paracorporeal artificial lung (PAL) was redesigned and built by MC3 (Ann Arbor, MI) in Phase I. The current PAL prototype in a pulmonary artery-to-pulmonary artery (PA-PA) configuration supported gas exchange in normal sheep (N=8) for up to 7 days. Additionally, 7/8 sheep achieved total gas exchange (02 and CO2) for 3 days following a lethal (LD100) smoke/burn injury. Our central hypothesis is that total extracorporeal gas exchange with the Optional Assisted Compliance Chamber (OACC) PAL will allow long-term respiratory support to achieve lung recovery from ARDS or bridge to lung transplant in patients with or without pulmonary hypertension. PHASE II Specific Aim 1: Develop an OACC to provide timed mechanical assist to right heart ejection. Since most patients with pulmonary disease have some degree of associated pulmonary hypertension, (often transiently severe) PAL must be able to provide total gas exchange (02 and CO2) and circulatory augmentation (primarily to the right ventricle). Specifically, using tightly coupled experimental and mathematical models (as outlined in the application); we will optimize the design of the OACC and PAL. The PAL will be able to overcome up to a 4-fold increase in pulmonary vascular resistance. We will

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determine the volume, pressure and cardiac cycle timing to optimize right ventricular support for application of PAL for pulmonary hypertension or right heart failure. Specific Aim 2" Design and fabricate injection molds for the preclinical production of PAL. Specific Aim 3: Utilizing our recently developed, clinically relevant LD100 sheep model of lethal ARDS, determine outcomes and measure injury parameters in two prospective randomized groups (N=10) over 10 days: 1) low tidal volume (LTV) ventilator management versus 2) PAL. Specific Aim 4: Investigate PAL impact on the pathophysiology of a lethal (LD100) smoke/burn induced lung injury randomized to PAL (N=10) or LTV ventilator management (N=10) then sacrifice at 48 degrees for full pathologic study. The knowledge gained will provide unique insight into the pathophysiology of ARDS and yield outcomes data for final PAL preclinical development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS TRANSPLANT

OF

CHRONIC

REJECTION

IN

LUNG

Principal Investigator & Institution: Fernandez, Felix G.; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-2002 Summary: (provided by the applicant): The long term survival and function of transplanted lungs are limited by the development of bronciolitis obliterans syndrome (BOS), an unexplained often nonreversible condition unresponsive to therapy and in most cases fatal. Over the past two years, compelling evidence has been obtained that the development of anti-HLA antibodies against mismatched donor antigens and the detection of in vivo priming against mismatched donor HLA class I antigens defined by indirect antigen presentation assays have significant correlation with the development of BOS. The first specific aim of this proposal is to demonstrate increased frequencies of donor reactive T cells prior to the appearance of anti-HLA antibodies in lung transplant recipients. This will be done by testing recipient peripheral blood leukocytes with donor mismatched HLA class I and II peptides in the presence of autologous antigen presenting cells in a proliferation assay. Therefore, in vitro methods to detect in vivo priming against mismatched donor HLA class land II antigens may serve as a good measure of successful intervention by changes in immunotherapeutic protocols. The second specific aim of this proposal is to define the biology and biochemistry of this newly identified airway epithelial antigen and to correlate the development of antigen specific antibodies with the development of BOS. A panel of airway epithelial cells (AECs) and the AEC specific silo antibodies developed post transplant will be used to define the polymorphism of this antigenic system. Using internal labeling of AEC and immunoprecipitation analysis using alloantibodies specific for AEC antigen, the biochemistry of this antigen will also be defined. The overall goals of this proposal are to continue to define the cellular and molecular mechanisms contributing to the development of BOS subsequent to lung transplantation and to allow the institution of new therapeutic strategies which will prevent the development and consequences of BOS, a major limiting factor for the continued function of the transplanted organ. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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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 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: PREDICTING DEATH IN CF PATIENTS AWAITING LUNG TRANSPLANT Principal Investigator & Institution: Belkin, Richard A.; Pediatrics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 24-JUL-2003; Project End 23-JUL-2005 Summary: (provided by applicant) The traditional referral guidelines for lung transplant in CF are largely based on a FEV <30% predicted. The optimal timing for referral has not been determined. Other factors may be important in predicting the risk of death in these patients. The presence of emerging infectious CF pathogens may be associated with a higher risk of death. These factors have not been tested in other studies. The identification of the above variables as risk factors for death may be used to modify the referral process or pre-transplantation therapy and improve survival of CF patients awaiting transplantation. We propose to perform a three-center retrospective

32

Lung Transplant

cohort study, with the following aims: (1) determine the association of emerging CF pathogens (including Aspergillus spp. And MRSA) pretransplant with mortality while awaiting lung transplantation: before and after referral for lung transplantation, (2) determine the association of poor nutritional status (including shorter height) pretransplant with mortality while awaiting lung transplantation (3) determine the association of poor pulmonary function (including % predicted FEV1) pretransplant with mortality while awaiting lung transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREDICTORS OF QUALITY OF LIFE: LUNG TRANSPLANT PATIENTS Principal Investigator & Institution: Lanuza, Dorothy M.; Visiting Professor; None; Loyola University Chicago Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 30-APR-2005 Summary: The quality of the lung transplant recipient's life over time remains relatively unexplored. To date, the majority of the studies on QOL of lung transplant patients can be characterized as primarily cross-sectional, limited in scope, and lacking congruence between conceptualization and measurement of QOL, making comparisons within and between studies difficult. Overall Aims: To examine the QOL of lung transplant patients before and up to 1 year after lung transplantation, as measured by indicators of both physical and psychological functioning; and to identify factors that are predictive of QOL outcomes during the first year post-transplant. The specific aims of this study pre- and during the first year post transplant are: I. To ascertain the impact of lung transplantation on subjects' physical functioning as reflected by: 1) physiologic variables (e.g., forced expiratory volume in 1 second [FEV1], blood pressure [BP], heart rate [HR]); 2) distance walked in 6-minute walk test; 3) number of infection and rejection episodes; 4) perceived physical functioning (physical functioning subscales of Sickness Impact Profile [SIP] and Quality of Life Index [QOLI]); and 5) satisfaction with perceived physical functioning (General Health Satisfaction Scale). II. To ascertain the impact of lung transplantation on subjects' psychosocial functioning as reflected by: 1) psychosocial and emotional well-being (e.g., Brief Symptom Inventory [BSI] and psychosocial subscales of SIP and QOLI); 2) symptoms (e.g., Transplant Symptom Inventory, Dyspnea Visual Analogue Scale); 3) treatment adherence (Treatment Adherence Scale); 4) satisfaction with general health (General Health Satisfaction Scale). III. To identify predictors (e.g., gender) of QOL outcomes and survival during the first year post-transplant. IV. To investigate lung transplant sub-group differences (e.g., gender) in QOL outcomes and symptom experiences. V. To delineate the role of select circadian rhythms (BP and HR) as independent predictors of QOL post-transplant. Statistical Analysis: Descriptive and inferential statistics (e.g., repeated measures ANOVA, McNemar, and Wilcoxon rank sum test), and co-sinor and harmonic analysis for circadian rhythms will be used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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33

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 •

Project Title: INFECTIONS/TRANSPLANTATION

PREVENTION/DIAGNOSIS/FUNGAL

Principal Investigator & Institution: Alexander, Barbara D.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): The incidence of invasive fungal infections (IFIs) has increased dramatically over the past twenty years. Patients undergoing bone marrow transplantation (BMT) as well as those receiving transplanted solid organs are at particularly high risk for these often lethal infections. IFIs are associated with high mortality owing to currently limited and often toxic antifungal drugs as well as the lack of sensitive, rapid tests to aid in the earlier diagnosis of invasive fungal infections. If an antifungal regimen could be given safely to patients at high risk for developing fungal infections and fungal infections prevented without inducing the development of resistance, the field of transplantation would benefit greatly. Similarly, if an assay could be developed that would reliably diagnose invasive mycoses early in the course of infection, targeted antifungal regimens could be started at a stage of infection more amenable to therapy. The specific aims of this proposal are 1) to assess new prophylactic regimens for the prevention of invasive fungal infections in high risk transplant populations and 2) to assess new laboratory assays for the rapid diagnosis of invasive fungal infections in high risk populations. These aims will be met through a series of clinical trials. The safety and tolerability of inhaled Amphotericin B Lipid Complex (ABLC) will be determined in the allogeneic BMT population through a nonrandomized open-label trial. Large, multicenter randomized, trials designed to assess efficacy will follow. The inhaled route of administration of ABLC for prophylaxis may result in a decreased incidence of toxicity as compared with the systemic administration of the drug. The performance characteristics and the diagnostic value of serial monitoring with different rapid antigen assays and PCR assays will be assessed in prospective studies involving lung transplant recipients. Trials designed to investigate the contribution of these rapid assays to better clinical outcomes will follow. Finally, a multicenter transplant data registry and specimen bank will be established for the purpose of evaluating rapid diagnostic assays currently in development. This approach will shorten the time from development to clinical implementation in therapeutic trials and guidelines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTECTION OF THE PULMONARY VASCULAR ENDOTHELIUM Principal Investigator & Institution: Kron, Irving L.; Professor; Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-JUL-1997; Project End 30-APR-2007 Summary: (provided by applicant): This proposal examines the role of neutrophils, lung-resident macrophages, and nitric oxide in pulmonary ischemia reperfusion (I/R) injury. Three specific hypotheses will be tested. (1) pulmonary macrophages play a

34

Lung Transplant

major role in lung I/R injury, and this injury is increased by a relative lack of NO which normally suppresses macrophage cytokine production; (2) Activation of adenosine 2A (A2A) receptors can substantially reduce lung I/R injury; the role of NO in mediating the biological effects of A2A receptor activation in lung I/R injury will be studied; (3) reperfusion injury increases the risk of subsequent acute and chronic rejection. Studies to test these hypotheses will be performed in a blood-perfused rabbit lung model of I/R, a rat model of lung I/R injury, a mouse isolated lung I/R model, and a porcine lung transplantation model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUALITY OF LIFE IN ADVANCED CF IN A TRANSPLANTATION ERA Principal Investigator & Institution: Robinson, Walter M.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 04-JUN-2003; Project End 31-MAY-2008 Summary: (provided by investigator): Cystic fibrosis (CF), the most common lethal inherited illness among Caucasians in North America, is undergoing a revolution. The advent of lung transplantation, while offering a chance at extended life for many patients, has undone the previous consensus on the appropriate treatment of end-stage symptoms, the use of assisted ventilation, and the management of psychosocial suffering. In order to answer the call of the Institute of Medicine for the integration of palliative care into chronic and ultimately fatal illnesses, a comprehensive study of the care of patients with end-stage cystic fibrosis is proposed. The purpose of the proposed study is to gather empirical data on the experiences of CF patients, their families, and caregivers during the final years of life. The specific aim is to understand the quality of life and the social and logistical needs of CF patients and their families, and to understand how the these factors may differ depending on the patient's end-of-life trajectory. The approach for addressing these questions will be a three-year longitudinal panel study of adult CF patients with advanced disease. Ten CF centers from across the United States will enroll adult patients with a predicted life expectancy of two to three years; these patients will be followed in a prospective manner for 36 months. The study will employ three methods of data collection: (1) self-administered surveys of patients, (2) telephone interviews with patients, family members of patients who die, and clinicians, and (3) medical record abstraction. Expected outcomes from this research will be decreased suffering and enhanced quality of life for CF patients, guidelines for the appropriate use of technological interventions for patients both on and off the transplant list, new care models that can accommodate both the goals of transplantation and the goals of palliative care, better systems of care for the families of seriously ill CF patients, and increased understanding of the role of palliative care and technological intervention in other chronic, ultimately fatal illnesses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUALITY OF LIFE IN PATIENTS WITH SEVERE CYSTIC FIBROSIS Principal Investigator & Institution: Goss, Christopher H.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by the applicant):Cystic Fibrosis (CF) is one of the most common inherited fatal diseases. Over the past thirty years, the median age of survival has improved from 14 years in 1969 to 29.1 years (95% Cl's 27.5 to 31.6) in 1999 in the United

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States. With this improved survival, this disease has been transformed from a disease with very high infant mortality to a disease that must now be considered a chronic and progressive lung disease. Improving the survival in these patients has been the primary goal over the last 30 years, but now clinical researchers must broaden their assessment of outcome in this disease to include patient-oriented outcomes such as health-related quality of life. Unfortunately, there is very limited research on the utility and relative strengths of different methods to measure health-related quality of life in patients with CF, especially for that group with the most severe disease. A better understanding of the best instruments, the minimal clinically important difference of these instruments, and the course of quality of life in these patients is needed in order to assess the value of treatments and interventions and to counsel patients and their families about their prognosis and the morbidity associated with this disease. This application proposes a prospective cohort study of patients with severe CF. Four different health-related quality of life instruments will be assessed, including a recently developed CF specific quality of life instrument. Patients will be evaluated at 6 month intervals f or a total of three years. The overall object of this proposal is to advance the state of the art in the measurement of health-related quality of life in adolescent and adult patients with severe cystic fibrosis in order to facilitate development and assessment of treatments that improve the quality of patients' lives and help predict the best time for evaluation for a lung transplant. In addition, this application proposes to compare the baseline differences health-related quality of life in patients not listed for lung or heart lung transplant, listed for lung or heart lung transplant, and transplanted and how healthrelated quality of life changes through time in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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Lung Transplant

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: RISK FACTORS & BIOMARKERS OF OX STRESS IN GRAFT FAILURE Principal Investigator & Institution: Christie, Jason D.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 08-FEB-2000; Project End 31-DEC-2004 Summary: The candidate plans a career as a clinical epidemiologist focusing on translational research, bridging basic science and clinical pulmonary medicine. Training will include formal epidemiological course work toward a Master's degree, a mentored laboratory experience, and closely mentored completion of the research protocol. The University of Pennsylvania is a uniquely suited environment for this training award. The Center for Clinical Epidemiology and Biostatistics will provide formal coursework and structured mentoring. The clinical and laboratory Cores of the NHLBI Acute Lung Injury SCOR grant will provide research support. Primary graft failure (PGF) is a devastating acute lung injury syndrome following lung transplantation, which complicates up to 35 percent of all lung transplants. The predominant mechanism underlying this response is currently felt to be ischemia-reperfusion injury. PGF has a profound impact on outcomes following lung transplantation, markedly increasing length of hospitalization, length of time requiring mechanical ventilation, mortality and overall cost. Despite the clear importance of PGF, little is known of the donor and recipient risk factors or pathophysiologic mechanisms contributing to this devastating syndrome. This protocol describes an investigation of the clinical and biologic risk factors for development of primary graft failure. As well, the protocol aims to shed light on the basic mechanisms of PGF by focusing on the role of oxidant stress. The study has three specific aims: (1) to examine the relationship between clinical parameters and the incidence of PGF; (2) to test the hypothesis that elevated plasma levels of selected biomarkers of oxidant stress in the lung transplant donor and recipient are preoperative risk factors for the development of PGF; (3) to test the hypothesis that elevated postoperative levels of selected biomarkers of oxidant stress coincide with development of PGF. Clinical risk factors will be evaluated by carrying out a retrospective cohort study of all lung transplants at the University of Pennsylvania Medical Center. Analysis will include univariate and multivariable explanatory models, and a clinical prediction

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rule will be developed. Biomarkers will be evaluated as risk factors and as coinciding with the development of PGF by carrying out a prospective cohort study. This protocol will provide new insights into the clinical risk factors for the development of PGF, will evaluate biomarkers of oxidant stress for its early detection, and may provide a mechanistic basis for new approaches to specific therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF COAGULATION AND PULMONARY XENOGRAFT INJURY Principal Investigator & Institution: Cantu, Edward; Surgery; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 08-JUL-2002 Summary: (provided by applicant): Our purpose is to determine the role of coagulation system activation and inadequate regulation within the pulmonary xenograft on endothelial cell activation, inflammatory augmentation and pulmonary xenograft injury. Initiation of the coagulation system coincides with the acute lung injury that is caused by a) ischemia-reperfusion b) complement activation c) probably antibody binding and d) the pro-coagulant and anti-fibrinolytic actions of pulmonary macrophages. Coagulation system dysregulation allows for uncontrolled acceleration of coagulation with cascading effects on the endothelial cell and the inflammatory system. Strategies to decrease the initiating events leading to activation of the coagulation system are our focus. We plan to 1) deplete the pulmonary macrophages by repetitive administration of intravenous liposomal clodronate to determine their role in initiation of the diffuse intravascular coagulation, endothelial cell activation, and pulmonary xenograft injury 2) determine the importance of xenoreactive antibody binding to Gala1 -3Gal epitopes in pulmonary xenograft injury by depleting antibody in the absence of complement activation using a-gal trisaccharide-PEG conjugates in conjunction with complement inhibition using C1-inhibitor and anti- C5a and 3) inhibit and regulate the coagulation system through the use of inhibition of tissue factor dependent activation of factors IX and X using TFPI or ASIS, and inhibition of factor VIlla and Va by Activated Protein C to assess the effects on endothelial cell function, inflammatory system activation and xenograft function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SDZ RAD IN STABLE LUNG TRANSPLANT RECIPIENTS WITH CYSTIC FIBROSIS Principal Investigator & Institution: Loyd, James E.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 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: SKELETAL MUSCLE DYSFUNCTION IN COPD Principal Investigator & Institution: Systrom, David M.; Assistant Professor and Associate Physic; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 30-NOV-2004 Summary: Chronic obstructive pulmonary disease (COPD) affects 14 million people in the United States, is a major source of morbidity and mortality and drains increasing

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Lung Transplant

scarce health care resources. The overall aim of this project is to better understand reduced exertional tolerance in COPD, which in turn, is related to its morbidity and mortality. Recent published and pilot data from our laboratories suggest a major reason for reduced aerobic capacity in COPD is not abnormal lung function per se, but decreased oxidative capacity of peripheral skeletal muscle itself. Using classic measures of oxygen delivery and utilization during exercise, we have demonstrated a clinically relevant problem with systemic O2 uptake in COPD, which does not improve with ventilatory muscle unloading, after volume reduction surgery or after lung transplantation. These data are consistent with an abnormality of either microcirculatory matching of blood flow and metabolism in the limb muscle or to an inherent defect in the muscle mitochondrion. Our laboratories have developed a new magnetic resonance imaging plethysmographic and T1-weighted measurements of both global and regional peripheral muscle perfusion, which have demonstrated abnormalities in congestive heart failure patients. We have also utilized state of the art 31P magnetic resonance spectroscopy techniques and found abnormal pHi regulation during exercise in the lung transplant recipient's skeletal myocyte, suggestive of an oxidative myopathy. The specific propose of this project is to identify patients with severe COPD and abnormal systemic O2 extraction and to then differentiate between abnormalities of skeletal muscle perfusion and an intrinsic mitochondrial defect as an explanation for their limit to exercise. {Through statistical analysis, we will determine associations among abnormal O2 extraction and smoking history, nutrition, hypoxemia and corticosteroid use.} Having identified patients with abnormal skeletal muscle O2 extraction, we will seek to differentiate disorders of regional blood flow to the exercising limb from intrinsic abnormalities of the muscle mitochondrion as a cause and {determine whether such abnormalities are related to detraining}. Better understanding of the skeletal muscle oxidative abnormality in COPD will provide a rational basis for new therapies in this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SKELETAL TRANSPLANT

MUSCLE

FUNCTION

PRE-

AND

POST-LUNG

Principal Investigator & Institution: Rossiter, Harry B.; Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2004; Project Start 09-FEB-2004; Project End 08-FEB-2006 Summary: (provided by applicant): Before lung transplant (LTx), exercise limitation in emphysema is predominantly due to ventilatory impairment and muscle detraining. Maximum O2 uptake and lactate threshold are substantially reduced: about 30 percent of predicted. It is, therefore, stunningly disappointing that after LTx, and in spite of normalization of lung function, exercise capacity is no better than about 50 percent of normal. Mechanisms of this impairment may include: disuse atrophy, myopathy from corticosteroid use, mitochondrial myopathy, or a result of immunosuppressive therapy. The true potential of the muscles often goes untested using whole-body exercise as the lung disease limits muscle O2 delivery. Therefore, we will exercise only a small musclemass: single-leg knee-extensors. Muscle function will be assessed by a multidisciplinary array including: muscle blood flow, O2 utilization, intramuscular magnetic resonance spectroscopy, and structural, biochemical and molecular analysis of biopsies. Assessment will be made both before and after knee-extensor training and before and after LTx. We hypothesize that: 1) pre-LTx, muscle dysfunction is due to disuse and will be restored to the normal range by training, even as emphysema persists; and 2) postLTx, immunosuppressive therapy results in muscle myopathy such that similar training

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will not result in normalization of function. Parallel animal studies of the regulation of angiogenic and hypertrophic genes during immunosuppression will also be made. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURGICAL TREATMENT OF CARDIAC ARRHYTHMIAS Principal Investigator & Institution: Boineau, John P.; Medical Science Service; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 08-AUG-1983; Project End 31-JUL-2003 Summary: This renewal application requests five years' support for work now in continuous progress for over 15 years at Washington University. Dr. John Boineau, the new PI, has replaced Dr. James Cox, the former P1, who transferred to Georgetown University Hospital. Dr. Cox remains as a special consultant. The broad aims continue to be the direct or surgical ablation of cardiac arrhythmias. The emphasis of the current renewal is focused upon the development of a new procedure, the radial incisions approach (RIA), to eradicate atrial fibrillation (AF) and restore atrial transport function and is directed primarily toward patients undergoing surgery for valvular or ischemic heart disease. Conventional valve or CABG surgery does not eliminate and may not prevent AF in these patients. The availability of an effective means of eradicating this arrhythmia in these patients at the time of surgery would permit control of rate and rhythm, limit embolic stroke, and improve cardiac performance, outcome, and the quality of life. Whereas the Maze and RIA assume randomly distributed and changing reentry which are eliminated without prior activation mapping, new data indicate that some forms of AF result from (spatially) stable reentry which can be identified by new mapping methods and focally ablated. Thus, a second project is directed toward map guided, focal cryoablation of AF. This could be performed off bypass as a more limited and rapid alternative to the more extensive and (bypass) time consuming RIA procedure. A third project is targeted at prevention and correction of postoperative atrial flutter (AFL) after the Fontan operation in congenital heart patients or after lung transplant surgery. Studies will be performed in both realistic animal models with atrial enlargement and patients with AF and AFL and will center about the use of new automated, 3-D mapping techniques and rapid numerical analysis of potentials recorded simultaneously from to 512 electrodes during the arrhythmias. Preliminary observations indicate that the proposed studies are feasible, will provide new information regarding the different mechanisms of AF and AFL that are related to atrial enlargement and/or atrial surgery, and this data will be used to develop the new surgical ablation techniques to control or prevent these arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYMPTOMS TRANSPLANT

OF

ACUTE

COMPLICATIONS

AFTER

LUNG

Principal Investigator & Institution: De Vito Dabbs, Annette J.; Acute/Tertiary Care; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 30-APR-2003 Summary: The majority of lung transplant recipients experience improvement in the symptoms of their chronic pulmonary condition following lung transplantation, but are faced with the specter of new symptoms that invariably develop due to the devastating complications of rejection and infection. Clinicians are aware of the signs of these complications, and a plethora of studies have been published describing their incidence and impact. However, the precise characteristics and influencing factors of symptoms

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Lung Transplant

that cause distress, interfere with performance, or forewarn of impending complications are unknown. The purpose of this study is to describe the symptoms of acute complications after lung transplant and to identify the influencing factors. Methodological triangulation will e used to describe the symptom experience. Recipients will complete a symptom inventory and be interviewed to obtain their description of the symptoms and influencing factors they experience at intervals that coincide with evaluations for episodes of acute complications. Quantitive measures of physiological factors (pulmonary function, rejection, and infection), situational factors (time after transplant, immunosuppression regimen), and psychological factors (anxiety, depression) will be obtained at the same time intervals to determine their influence on symptomatology. Matrix analyses of qualitative and quantitative data will be performed to reveal factors that influence the symptom experience. The Theory of Unpleasant Symptoms provides a theoretical basis which nurses use to identify symptoms and their influencing factors, and design and evaluate interventions aimed at reducing the manifestations of symptoms and improving patient outcomes. Knowledge of the symptom experience of lung transplant recipients will provide the foundation for nurses to study the effects of interventions designed to detect and manage symptoms associated with acute complications after lung transplant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TELEPHONE STRESS MANAGEMENT FOR LUNG TRANSPLANT PATIENTS Principal Investigator & Institution: Blumenthal, James A.; Professor; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (adapted from investigator's abstract): Lung transplantation is a relatively new procedure developed to increase life expectancy in selected individuals with irreversible end-stage lung disease. In the brief period since its inception, it appears that lung transplantation has achieved its initial aim of extending life. Despite these successes, lung transplantation remains fraught with difficult challenges for the patient and the medical community. The pre-surgical waiting period is a particularly stressful time. The long, uncertain wait for an organ, the marked decline in functional capacity, the tremendous financial burden, and the prospect of a complicated medical regimen after surgery, combine to exert a profound strain on patients' coping capacities. Not surprisingly, the rate of clinically significant psychological distress during this period is quite high, with rates of clinical depression, panic, anxiety and adjustment disorders far exceeding those observed in the general population. Although it is well established that brief, focused cognitive-behavioral therapy (CBT) can significantly improve psychological function in medically ill persons, the wide geographic distribution of transplant patients, along with their marked debilitation makes face-to-face delivery of such therapy extremely difficult. Recent pilot data have demonstrated the feasibility and short-term efficacy of a telephone-based psychological intervention with patients awaiting transplant. A larger, dual-site (Duke and Washington University), randomized trial using a relatively comprehensive set of outcome measures, over an extended follow-up period is proposed in which 600 pre-surgical lung transplant patients will be randomly assigned to either a telephone-based CBT intervention or to usual care. The study will examine the short- and longer-term impact of the intervention on psychological distress and quality of life as well as the effects of the intervention on morbidity, mortality, and medical costs during the pre- and post-operative periods. If the intervention is successful, it may serve as a model for the delivery of home-based,

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cost-effective treatment for seriously ill patients unable to benefit from more traditional face-to-face psychotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRACKING ANTIGEN SPECIFIC T CELLS DURING GRAFT REJECTION Principal Investigator & Institution: Jenkins, Marc K.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: (provided by the applicant): CR associated with fibrosis is a major cause of allograft failure since the advent of immunosuppressive drugs that block acute rejection. The hypothesis to be tested here is that CR is driven by T cells that are stimulated by donor antigen peptides presented by APC of the recipient at a time when surgery related inflammation has waned. It is further proposed that this environment causes donor antigen peptide specific T cells to differentiate into type 2 lymphokine (IL-4, IL-5, IL-6, IL-10) producing cells. These lymphokines are proposed to directly or indirectly cause fibrosis within the graft. This hypothesis will be tested using a novel C57BL/6 (B6) Tg mouse line that expresses ovalbumin (OVA) on all cells of the body. Preliminary results show that skin grafts from OVA B6 donors are acutely rejected by B6 recipients in a T cell dependent fashion. In the first aim, an attempt will be made to identify conditions that convert this process into CR by treating recipients with cyclosporine A to allow OVA B6 skin grafts to survive the period of surgery related inflammation, by forcing antigen presentation by recipient APC by removing MHC molecules from OVA B6 donors, and by grafting OVA B6 tracheas that undergo CR naturally. In the second aim, the conditions that result in CR will be used to determine which T lymphocyte subset is responsible and whether or not these cells produce type 2 lymphokines. This approach will be strengthened by the use of adoptive transfer of OVA reactive TCR transgenic CD4 and CD8 T cells to physically track the location and function of specific T cells during CR. The experiments proposed in the third aim will rely on IL-4 deficient recipients and IL-12 administration to test a causal relationship between type 2 lymphokine production by graft antigen specific T cells and the subsequent fibrosis that impairs graft function. It is hoped that an improved understanding of the immunological processes that underlie CR will lead to therapies aimed at graft antigen specific tolerance or treatment of fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSLATIONAL REPRESSORS AS THERAPY FOR OB Principal Investigator & Institution: Bitterman, Peter B.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: (provided by applicant): Chronic allograft rejection shares a common pathophysiological feature in each organ studied: accumulations of mesenchymal cells in critical lumena leading to organ dysfunction. In the course of experiments examining the ability of HMG-CoA reductase inhibitors to selectively induce apoptosis in fibroblasts with deregulated growth control, we discovered a key role for the capdependent translation initiation apparatus in the regulation of fibroblast viability. In mammals, a bimolecular complex designated eIF4F initiates cap-dependent translation. It consists of three proteins: eIF4E, which binds the 7-methyl guanosine cap at the 5' mRNA terminus and is generally considered to be present in rate limiting amounts;

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eIF4A, an mRNA helicase; and eIF4G, which serves as a docking protein binding eIF4E and eIF4A as well as the adapter protein eIF3 which targets the intact eIF4F complex to the 40S subunit of the ribosome. Translation initiation factor 4E is regulated by a family of repressor proteins, the 4E-BPs, which share a motif with eIF4G allowing them to sequester eIF4E in a competitive manner. Phosphorylation of the 4E-BPs decreases their affinity for eIF4E, freeing it to bind eIF4G and initiate translation. Most importantly from a therapeutic point of view, we have found that fibroblasts with deregulated growth have an increased requirement for cap-dependent translation to suppress apoptosis in vitro and in vivo, when compared to normal fibroblasts. Thus, here we propose to take the first step toward developing therapies for the lumenal airway fibrosis characteristic of lung allograft rejection. We will test the hypothesis that transfer of genes encoding translational repressors operating at the apical step of cap-dependent translation initiation will selectively chemosensitize fibroblasts in airway allograft fibrosis to safe doses of HMG-CoA reductase inhibitors, without harming desirable parenchymal bystanders. We propose 2 Specific Aims: 1) Use the known crystal structure of eIF4E to develop, validate and transfer gene constructs in vitro that lead to loss of translation initiation factor 4E (eIF4E) function; and test their ability to chemosensitize fibroblasts to HMG-CoA reductase inhibitor-induced apoptosis; 2) Starting with wild type 4E-BP1, systematically test whether transfer of genes encoding those translational repressors found to be proapoptotic in Aim 1 will collaborate with HMG-CoA reductase inhibitors to diminish airway lumenal narrowing in a well established murine allograft model of airway fibroproliferation. The proposed experiments are designed to test "proof of concept", an essential first step toward identification of novel molecular targets for drug discovery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF EBV ASSOCIATED LYMPHOPROLIFERATIVE DISEASE Principal Investigator & Institution: Moss, Denis J.; Queensland Institute of Medical Research Herston Brisbane Qld, 4006 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease in solid organ transplant patients poses a considerable challenge due to the underlying immunosuppression which inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. Preliminary studies developed in our laboratory suggest that it may be possible to overcome this inherent problem using a novel protocol to activate autologous EBV-specific CTL lines from these patients and to show for the first time their potential use for immunotherapy against PTLD in solid organ transplant patients. To establish the clinical use of this protocol, we propose to conduct a phase I/II clinical trial in a cohort of solid organ transplant patients with PTLD. To achieve this, we have drawn together scientific expertise within the EBV Unit at QIMR and major transplant units in Australia. In the first instances, we propose to further refine the in vitro conditions for activating EBV-specific CTL from solid organ transplant patients who are on high levels of immunosuppression. Two absolute requirements have been set: (1) EBV specificity at the CTL peptide epitope level; and (2) complete lack of anti-donor alloreactivity which would threaten the integrity of the transplanted graft. Having defined these conditions, we propose to conduct a phase I/II trial by adoptively transferring autologous EBV-specific CTL into solid organ heart, lung, and heart/lung transplant patients with PTLD. As far as we are aware, this represents the first such trial to be conducted and seeks to (1) determine the safety of adoptively transferring EBV-

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specific CTL into solid organ transplant patients; (2) determine the longevity of these CTL in vivo using a genetic marker; and (3) determine the extent of clinical regression of PTLD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “lung transplant” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lung transplant in the PubMed Central database: •

Direct Quantification of Human Cytomegalovirus Immediate-Early and Late mRNA Levels in Blood of Lung Transplant Recipients by Competitive Nucleic Acid Sequence-Based Amplification. by Greijer AE, Verschuuren EA, Harmsen MC, Dekkers CA, Adriaanse HM, The TH, Middeldorp JM.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87710

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Humoral immune response against human cytomegalovirus (HCMV)-specific proteins after HCMV infection in lung transplantation as detected with recombinant and naturally occurring proteins. by van Zanten J, Harmsen MC, van der Giessen M, van der Bij W, Prop J, de Leij L, The TH.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170130

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Invasive Fungal Sinusitis Caused by Scytalidium dimidiatum in a Lung Transplant Recipient. by Dunn JJ, Wolfe MJ, Trachtenberg J, Kriesel JD, Orlandi RR, Carroll KC.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=309010

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Novel Bacterium Isolated from a Lung Transplant Patient with Cystic Fibrosis. by Pitulle C, Citron DM, Bochner B, Barbers R, Appleman MD.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85827

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

5

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

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A longitudinal study of lung transplant recipients infected with Aspergillus: genetic polymorphism of A fumigatus. Author(s): Symoens F, Bertout S, Piens MA, Burnod J, Renaud F, Nolard N, Chapuis F, Grillot R; EBGA [European Group for Research on Biotypes and Genotypes of Aspergillus fumigatus] Network. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 September; 20(9): 970-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557192

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A review of lung transplant donor acceptability criteria. Author(s): Orens JB, Boehler A, de Perrot M, Estenne M, Glanville AR, Keshavjee S, Kotloff R, Morton J, Studer SM, Van Raemdonck D, Waddel T, Snell GI; Pulmonary Council, International Society for Heart and Lung Transplantation. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 November; 22(11): 1183-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585380

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A review of nutritional problems and the cystic fibrosis lung transplant patient. Author(s): Dosanjh A. Source: Pediatric Transplantation. 2002 October; 6(5): 388-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390424

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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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Achilles tendon disease in lung transplant recipients: association with ciprofloxacin. Author(s): Chhajed PN, Plit ML, Hopkins PM, Malouf MA, Glanville AR. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 March; 19(3): 469-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936524

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Acute postoperative pain in lung transplant recipients. Author(s): Richard C, Girard F, Ferraro P, Chouinard P, Boudreault D, Ruel M, Choiniere M, Poirier C, Girard DC. Source: The Annals of Thoracic Surgery. 2004 June; 77(6): 1951-5; Discussion 1955. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15172243

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Acute renal failure in a lung transplant patient after therapy with cidofovir. Author(s): Zedtwitz-Liebenstein K, Presterl E, Deviatko E, Graninger W. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2001 December; 14(6): 445-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793044

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Acute respiratory distress syndrome in a lung transplant recipient infected by a pUL97-mutated cytomegalovirus associated with decreased phosphorylation of ganciclovir. Author(s): Speich R, Gaspert A, Russi EW, Weder W, Boehler A. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(6): 564-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457014

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Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Author(s): Iacono AT, Corcoran TE, Griffith BP, Grgurich WF, Smith DA, Zeevi A, Smaldone GC, McCurry KR, Johnson BA, Dauber JH. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2004 March; 23(3): 384-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15065826

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Allergic bronchopulmonary aspergillosis in a lung transplant patient successfully treated with nebulized amphotericin. Author(s): Casey P, Garrett J, Eaton T. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 November; 21(11): 1237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431500

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Amphotericin B disposition after aerosol inhalation in lung transplant recipients. Author(s): Marra F, Partovi N, Wasan KM, Kwong EH, Ensom MH, Cassidy SM, Fradet G, Levy RD. Source: The Annals of Pharmacotherapy. 2002 January; 36(1): 46-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816256

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Amphotericin B in lung transplant recipients. Author(s): Klepser ME. Source: The Annals of Pharmacotherapy. 2002 January; 36(1): 167-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816247

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Anaemia in lung transplant patient caused by parvovirus B19. Author(s): Kariyawasam HH, Gyi KM, Hodson ME, Cohen BJ. Source: Thorax. 2000 July; 55(7): 619-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856324

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Anti-viral prophylaxis reduces the incidence of lymphoproliferative disease in lung transplant recipients. Author(s): Malouf MA, Chhajed PN, Hopkins P, Plit M, Turner J, Glanville AR. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 May; 21(5): 547-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983544

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Aspergillus and endobronchial abnormalities in lung transplant recipients. Author(s): Nathan SD, Shorr AF, Schmidt ME, Burton NA. Source: Chest. 2000 August; 118(2): 403-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936132

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Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole. Author(s): Lodge BA, Ashley ED, Steele MP, Perfect JR. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1376-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004125

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Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients. Author(s): Helmi M, Love RB, Welter D, Cornwell RD, Meyer KC. Source: Chest. 2003 March; 123(3): 800-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12628881

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Association of cytomegalovirus DNA concentration in epithelial lining fluid and symptomatic cytomegalovirus infection in lung transplant recipients. Author(s): Zedtwitz-Liebenstein K, Jaksch P, Bauer C, Popow T, Klepetko W, Hofmann H, Puchhammer-Stockl E. Source: Transplantation. 2004 June 27; 77(12): 1897-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15223910

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Atelectasis--an unusual and late complication of lung transplant. Author(s): Zhao Y, Al-Kaade S, Keller CA, deMello DE. Source: Clinical Transplantation. 2002 June; 16(3): 233-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010150

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Avoidant coping with health problems is related to poorer quality of life among lung transplant candidates. Author(s): Myaskovsky L, Dew MA, Switzer GE, Hall M, Kormos RL, Goycoolea JM, DiMartini AF, Manzetti JD, McCurry KR. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2003 September; 13(3): 183-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14558632

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Balance between alveolar macrophage IL-6 and TGF-beta in lung-transplant recipients. Marseille and Montreal Lung Transplantation Group. Author(s): Magnan A, Mege JL, Escallier JC, Brisse J, Capo C, Reynaud M, Thomas P, Meric B, Garbe L, Badier M, Viard L, Bongrand P, Giudicelli R, Metras D, Fuentes P, Vervloet D, Noirclerc M. Source: American Journal of Respiratory and Critical Care Medicine. 1996 April; 153(4 Pt 1): 1431-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8616577

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Bayesian forecasting of oral cyclosporin pharmacokinetics in stable lung transplant recipients with and without cystic fibrosis. Author(s): Rousseau A, Monchaud C, Debord J, Vervier I, Estenne M, Thiry P, Marquet P. Source: Therapeutic Drug Monitoring. 2003 February; 25(1): 28-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548141

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beta-Herpesvirus (human cytomegalovirus and human herpesvirus 6) reactivation in at-risk lung transplant recipients and in human immunodeficiency virus-infected patients. Author(s): Michaelides A, Glare EM, Spelman DW, Wesselingh SL, Hoy JF, Mijch AM, Kotsimbos TC. Source: The Journal of Infectious Diseases. 2002 July 15; 186(2): 173-80. Epub 2002 June 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12134252

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Bilateral lung transplant: the procedure of choice for end-stage septic lung disease. Author(s): Rao JN, Forty J, Hasan A, Hilton CJ, Ledingham S, Parry G, Wardle J, Gould FK, Corris PA, Dark JH. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1622-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267445

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Bilateral lung transplantation via two sequential anterolateral thoracotomies. Author(s): Taghavi S, Birsan T, Pereszlenyi A, Kupilik N, Deviatko E, Wisser W, Steltzer H, Klepetko W. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1999 May; 15(5): 658-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10386413

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Bilateral sequential lung transplant for ectodermal dysplasia. Author(s): Smythe WR, Bridges ND, Gaynor JW, Nicolson S, Clark BJ, Spray TL. Source: The Annals of Thoracic Surgery. 2000 August; 70(2): 654-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10969696

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Bronchial anastomotic complications in lung transplant recipients: virtual bronchoscopy for noninvasive assessment. Author(s): McAdams HP, Palmer SM, Erasmus JJ, Patz EF, Connolly JE, Goodman PC, Delong DM, Tapson VF. Source: Radiology. 1998 December; 209(3): 689-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9844660

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Bronchial hyperresponsiveness in lung transplant recipients: lack of correlation with airway inflammation. Author(s): Liakakos P, Snell GI, Ward C, Johns DP, Bamford TL, Williams TJ, Walters EH. Source: Thorax. 1997 June; 52(6): 551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9227723

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Bronchial-atrial fistula after lung transplant resulting in fatal air embolism. Author(s): Karmy-Jones R, Vallieres E, Culver B, Raghu G, Wood DE. Source: The Annals of Thoracic Surgery. 1999 February; 67(2): 550-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197694

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Bronchiolitis obliterans is not the primary cause of death in pediatric living donor lobar lung transplant recipients. Author(s): Woo MS, MacLaughlin EF, Horn MV, Szmuszkovicz JR, Barr ML, Starnes VA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 May; 20(5): 491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343974

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Bronchiolitis obliterans organizing pneumonia (BOOP) in lung transplant recipients. Author(s): Chaparro C, Chamberlain D, Maurer J, Winton T, Dehoyos A, Kesten S. Source: Chest. 1996 November; 110(5): 1150-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8915212

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Bronchiolitis obliterans syndrome in lung transplant recipients: can thin-section CT findings predict disease before its clinical appearance? Author(s): Konen E, Gutierrez C, Chaparro C, Murray CP, Chung T, Crossin J, Hutcheon MA, Paul NS, Weisbrod GL. Source: Radiology. 2004 May; 231(2): 467-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128992

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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 in single lung transplant recipients--patients with emphysema versus patients with idiopathic pulmonary fibrosis. Author(s): Haider Y, Yonan N, Mogulkoc N, Carroll KB, Egan JJ. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 March; 21(3): 327-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897520

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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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Bronchioloalveolar lavage in the diagnosis of CMV pneumonitis in lung transplant recipients: an immunocytochemical study. Author(s): Solans EP, Yong S, Husain AN, Eichorst M, Gattuso P. Source: Diagnostic Cytopathology. 1997 April; 16(4): 350-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9143830

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Bronchoalveolar lavage macrophage and lymphocyte phenotypes in lung transplant recipients. Author(s): Ward C, Whitford H, Snell G, Bao H, Zheng L, Reid D, Williams TJ, Walters EH. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 October; 20(10): 1064-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595561

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Bronchodilator response at low lung volumes predicts bronchiolitis obliterans in lung transplant recipients. Author(s): Rajagopalan N, Maurer J, Kesten S. Source: Chest. 1996 February; 109(2): 405-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8620713

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Bronchogenic carcinoma in lung transplant recipients. Author(s): Stagner LD, Allenspach LL, Hogan KK, Willcock LC, Higgins RS, Chan KM. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 August; 20(8): 908-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502415

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Cardiopulmonary transplantation: experience of a lung transplant group. Author(s): Morales P, Almenar L, Torres JJ, Sole A, Vicente R, Ramos F, Morant P, Lozano C, Calvo V; Valencia Lung Transplant Group. Source: Transplantation Proceedings. 2003 August; 35(5): 1954-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962861

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Care before and after lung transplant and quality of life research. Author(s): Lanuza DM, McCabe MA. Source: Aacn Clinical Issues. 2001 May; 12(2): 186-201. Review. Erratum In: Aacn Clin Issues 2001 November; 12(4): Following Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11759547

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Case 4: bronchiolitis obliterans in a lung transplant recipient. Author(s): Villanueva J, Garrity ER. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 October; 19(10): 1014-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11202923

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Case 5: recurrent cytomegalovirus infection in a lung transplant recipient. Author(s): Villanueva J, Garrity ER. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 November; 19(11): 1122-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11077232

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Characteristics of photopheresis treatments for the management of rejection in heart and lung transplant recipients. Author(s): Khuu HM, Desmond R, Huang ST, Marques MB. Source: Journal of Clinical Apheresis. 2002; 17(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948703

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Citalopram and quality of life in lung transplant recipients. Author(s): Silvertooth EJ, Doraiswamy PM, Clary GL, Babyak MA, Wilkerson N, Hellegars C, Palmer SM. Source: Psychosomatics. 2004 May-June; 45(3): 271-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123855

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Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin. Author(s): McCurdy LH, Milstone A, Dummer S. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 July; 22(7): 745-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873542

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Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients. Author(s): Reynaud-Gaubert M, Thomas P, Gregoire R, Badier M, Cau P, Sampol J, Giudicelli R, Fuentes P. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 January; 21(1): 60-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788258

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Coexistence of acute cellular rejection and lymphoproliferative disorder in a lung transplant patient. Author(s): Longchampt E, Achkar A, Tissier F, Rabbat A, Audouin J, Molina TJ. Source: Archives of Pathology & Laboratory Medicine. 2001 November; 125(11): 1500-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11698014

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Comparison of Bayesian, classical, and heuristic approaches in identifying acute disease events in lung transplant recipients. Author(s): Troiani JS, Carlin BP. Source: Statistics in Medicine. 2004 March 15; 23(5): 803-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981676

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Comparison of outcomes of double and single lung transplantation for obstructive lung disease. The Toronto Lung Transplant Group. Author(s): Patterson GA, Maurer JR, Williams TJ, Cardoso PG, Scavuzzo M, Todd TR. Source: The Journal of Thoracic and Cardiovascular Surgery. 1991 April; 101(4): 623-31; Discussion 631-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2008100

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Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients. Author(s): Kelly J, Hurley D, Raghu G. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 April; 19(4): 355-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10775816

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Comparison of the efficacy and cost-effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients. Author(s): Weill D, Zamora MR. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 August; 19(8): 815-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10967278

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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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Critical care management of lung transplant recipients. Author(s): Bierman MI, Stein KL, Stuart RS, Dauber JH. Source: Journal of Intensive Care Medicine. 1991 May-June; 6(3): 135-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10147910

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CT manifestations of respiratory syncytial virus infection in lung transplant recipients. Author(s): Ko JP, Shepard JA, Sproule MW, Trotman-Dickenson B, Drucker EA, Ginns LC, Wain JC, McLoud TC. Source: Journal of Computer Assisted Tomography. 2000 March-April; 24(2): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10752884

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Current status of heart and lung transplantation. Author(s): Barr ML. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3564-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750516

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Cyclosporin drug-interaction-induced rhabdomyolysis. A report of two cases in lung transplant recipients. Author(s): Cohen E, Kramer MR, Maoz C, Ben-Dayan D, Garty M. Source: Transplantation. 2000 July 15; 70(1): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10919586

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Cyclosporine and itraconazole interaction in heart and lung transplant recipients. Author(s): Kramer MR, Marshall SE, Denning DW, Keogh AM, Tucker RM, Galgiani JN, Lewiston NJ, Stevens DA, Theodore J. Source: Annals of Internal Medicine. 1990 August 15; 113(4): 327-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2165371

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Cytopathology of pulmonary alveolar proteinosis complicating lung transplantation. Author(s): Gal AA, Bryan JA, Kanter KR, Lawrence EC. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2004 January; 23(1): 135-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734139

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Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance: a comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome. Author(s): de Haan A, van der Gun I, Hepkema BG, de Boer WJ, van der Bij W, de Leij LF, Prop J. Source: Transplantation. 2000 April 15; 69(7): 1434-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10798767

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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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Delay of CMV infection in high-risk CMV mismatch lung transplant recipients due to prophylaxis with oral ganciclovir. Author(s): Palmer SM, Grinnan DC, Diane Reams B, Steele MP, Messier RH, Duane Davis R. Source: Clinical Transplantation. 2004 April; 18(2): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15016133

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Delayed sternotomy wound infection due to Paecilomyces variotii in a lung transplant recipient. Author(s): Lee J, Yew WW, Chiu CS, Wong PC, Wong CF, Wang EP. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 October; 21(10): 1131-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398880

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Desire for control, coping, and quality of life in heart and lung transplant candidates, recipients, and spouses: a pilot study. Author(s): Kurz JM. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2001 September; 11(3): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11949467

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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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Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Author(s): Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML. Source: American Journal of Respiratory and Critical Care Medicine. 2002 December 15; 166(12 Pt 1): 1550-5. Epub 2002 August 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406843

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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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Development of an eating disorder in a 40 year-old male lung transplant candidate: a case study. Author(s): Chesler BE, Hsu LK. Source: The International Journal of Eating Disorders. 1995 March; 17(2): 205-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7757104

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Development of bronchiolitis obliterans syndrome despite blood chimerism in human lung transplant recipients. Author(s): Calhoun R, SivaSai KS, Sundaresan S, Trulock EP, Lynch JP, Patterson GA, Cooper JD, Mohanakumar T. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1999; 12(6): 439-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10654356

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Development of lymphocytotoxic antibodies among lung transplant recipients: preliminary results. Author(s): Reynaud-Gaubert ML, Mercier PJ, Thomas PA, Badier MM, Noirclerc MJ, Giudicelli RA, Fuentes PA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1998 October; 17(10): 980-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9811405

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Diagnosis of chronic lung transplant rejection by transbronchial biopsy. Author(s): Cagle PT, Brown RW, Frost A, Kellar C, Yousem SA. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1995 February; 8(2): 137-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7777473

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Diagnostic properties of transbronchial biopsy in lung transplant recipients who require mechanical ventilation. Author(s): Burns KE, Johnson BA, Iacono AT. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 March; 22(3): 267-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633693

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Diagnostic yield and therapeutic impact of flexible bronchoscopy in lung transplant recipients. Author(s): Chan CC, Abi-Saleh WJ, Arroliga AC, Stillwell PC, Kirby TJ, Gordon SM, Petras RE, Mehta AC. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1996 February; 15(2): 196-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8672524

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Diagnostic yield of screening colonoscopies in lung transplant candidates. Author(s): Singer LG, Weinacker AB, Levin L, Doyle RL, Theodore J. Source: Transplantation. 2001 August 15; 72(3): 530-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502989

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Direct quantification of human cytomegalovirus immediate-early and late mRNA levels in blood of lung transplant recipients by competitive nucleic acid sequencebased amplification. Author(s): Greijer AE, Verschuuren EA, Harmsen MC, Dekkers CA, Adriaanse HM, The TH, Middeldorp JM. Source: Journal of Clinical Microbiology. 2001 January; 39(1): 251-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11136779

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Distribution of ventilation in lung transplant recipients: evaluation by dynamic 3HeMRI with lung motion correction. Author(s): Gast KK, Puderbach MU, Rodriguez I, Eberle B, Markstaller K, Knitz F, Schmiedeskamp J, Weiler N, Schreiber WG, Mayer E, Thelen M, Kauczor HU. Source: Investigative Radiology. 2003 June; 38(6): 341-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908701

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Does previous thoracic surgery increase perioperative risk in lung transplantation? Author(s): Hirt SW, Rahimi A, Moller F, Hein M, Bottcher H, Cremer J. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3572-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750519

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Does splitting the lung block into two single lung grafts equate to doubling the societal benefit from bilateral lung donors? Comparisons between two single versus one bilateral lung transplant. UK Cardiothoracic Transplant Audit Steering Group. Author(s): Anyanwu AC, Rogers CA, Murday AJ. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2000; 13 Suppl 1: S201-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11111996

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Dose adjustment and cost of itraconazole prophylaxis in lung transplant recipients receiving cyclosporine and tacrolimus (FK 506). Author(s): Kramer MR, Merin G, Rudis E, Bar I, Nesher T, Bublil M, Milgalter E. Source: Transplantation Proceedings. 1997 September; 29(6): 2657-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9290780

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Early chimerism of macrophages and lymphocytes in lung transplant recipients is predictive of graft tolerance. Author(s): Rothmeier C, Roux E, Spiliopoulos A, Gerbase M, Nicod LP. Source: Transplantation. 2001 May 15; 71(9): 1329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11397972

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Early experience with sirolimus in lung transplant recipients with chronic allograft rejection. Author(s): Cahill BC, Somerville KT, Crompton JA, Parker ST, O'Rourke MK, Stringham JC, Karwande SV. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 February; 22(2): 169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581765

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Effects of sinus surgery in patients with cystic fibrosis after lung transplantation: a 10-year experience. Author(s): Holzmann D, Speich R, Kaufmann T, Laube I, Russi EW, Simmen D, Weder W, Boehler A. Source: Transplantation. 2004 January 15; 77(1): 134-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724449

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Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung Transplant Group. Author(s): Elssner A, Jaumann F, Dobmann S, Behr J, Schwaiblmair M, Reichenspurner H, Furst H, Briegel J, Vogelmeier C. Source: Transplantation. 2000 July 27; 70(2): 362-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933164

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Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients. Author(s): Bhorade SM, Lurain NS, Jordan A, Leischner J, Villanueva J, Durazo R, Creech S, Vigneswaran WT, Garrity ER. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 December; 21(12): 1274-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490272

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Endoscopic management of airway complications after lung transplantation. Author(s): Mulligan MS. Source: Chest Surg Clin N Am. 2001 November; 11(4): 907-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11780302

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Endoscopic repair of bronchial dehiscence after lung transplantation. Author(s): Maloney JD, Weigel TL, Love RB. Source: The Annals of Thoracic Surgery. 2001 December; 72(6): 2109-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11789804

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Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients. Author(s): Wimberley SL, Haug MT 3rd, Shermock KM, Qu A, Maurer JR, Mehta AC, Schilz RJ, Gordon SM. Source: Clinical Transplantation. 2001 April; 15(2): 116-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11264638

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Epstein-Barr virus primary mismatching and HLA matching: key risk factors for post lung transplant lymphoproliferative disease. Author(s): Wong JY, Tait B, Levvey B, Griffiths A, Esmore DS, Snell GI, Williams TJ, Kotsimbos TC. Source: Transplantation. 2004 July 27; 78(2): 205-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15280679

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Epstein-Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation. Author(s): Wigle DA, Chaparro C, Humar A, Hutcheon MA, Chan CK, Keshavjee S. Source: Transplantation. 2001 December 15; 72(11): 1783-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740388

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Estimation and comparison of derived preference scores from the SF-36 in lung transplant patients. Author(s): Lobo FS, Gross CR, Matthees BJ. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2004 March; 13(2): 377-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085910

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Evaluating the reliability and validity of the Questionnaire for Lung Transplant Patients. Author(s): De Vito Dabbs A, Hoffman LA, Dauber JH, Zullo T, Iacono AT. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2002 September; 12(3): 191-8; Quiz 199-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371045

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Evaluation with enzyme-linked immunosorbent assay spot detection of the frequency of interferon-gamma-producing T cells in bronchoalveolar lavage is useful in identifying lung transplant patients at higher risk of acute rejection. Author(s): Meloni F, Paschetto E, Cascina A, Marone Bianco A, Pellegrini C, Oggionni T, Vitulo P, Vigano M. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3286-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750407

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Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Author(s): Azzola A, Havryk A, Chhajed P, Hostettler K, Black J, Johnson P, Roth M, Glanville A, Tamm M. Source: Transplantation. 2004 January 27; 77(2): 275-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742993

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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): Behr J, Maier K, Braun B, Schwaiblmair M, Vogelmeier C. Source: Transplantation. 2000 May 15; 69(9): 1856-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10830222

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Evidence that humoral allograft rejection in lung transplant patients is not histocompatibility antigen-related. Author(s): Magro CM, Klinger DM, Adams PW, Orosz CG, Pope-Harman AL, Waldman WJ, Knight D, Ross P Jr. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 October; 3(10): 1264-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510700

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Evolving capnograms after single lung transplant. Author(s): Srinivasa V, Kodali BS, Hartigan PM. Source: Anesthesia and Analgesia. 2004 May; 98(5): 1504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15105248

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Expression dynamics of human cytomegalovirus immune evasion genes US3, US6, and US11 in the blood of lung transplant recipients. Author(s): Greijer AE, Verschuuren EA, Dekkers CA, Adriaanse HM, van der Bij W, The TH, Middeldorp JM. Source: The Journal of Infectious Diseases. 2001 August 1; 184(3): 247-55. Epub 2001 July 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443549

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Extracorporeal photopheresis in the treatment of persistent rejection in a pediatric lung transplant recipient. Author(s): Wise BV, King KE, Rook AH, Mogayzel PJ Jr. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2003 March; 13(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688651

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Factors contributing to mortality in lung transplant recipients: an autopsy study. Author(s): Cagle PT, Truong LD, Holland VA, Lawrence EC, Rogers BB, Schwartz MR, Kolda T, Buffone GJ, Noon GP, Greenberg SD. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1989 March; 2(2): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2657722

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Failure of ganciclovir treatment associated with selection of a ganciclovir-resistant cytomegalovirus strain in a lung transplant recipient. Author(s): Alain S, Honderlick P, Grenet D, Stern M, Vadam C, Sanson-Le Pors MJ, Mazeron MC. Source: Transplantation. 1997 May 27; 63(10): 1533-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9175826

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Fatal fat embolism syndrome after numerous vertebral body compression fractures in a lung transplant recipient. Author(s): Day JD, Walden SM, Stuart SR, Hutchins GM, Hruban RH. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1994 September-October; 13(5): 785-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7803419

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Fatal outcome of lung transplantation in cystic fibrosis patients due to small-colony variants of the Burkholderia cepacia complex. Author(s): Haussler S, Lehmann C, Breselge C, Rohde M, Classen M, Tummler B, Vandamme P, Steinmetz I. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 April; 22(4): 249-53. Epub 2003 March 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687415

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Fat-free mass change to weight change ratio during refeeding following lung transplantation. Author(s): Kyle UG, Nicod L, Raguso C, Hans D, Pichard C. Source: Acta Diabetologica. 2003 October; 40 Suppl 1: S165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618462

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FEV(1) as a guide to lung transplant referral in young patients with cystic fibrosis. Author(s): Robinson W, Waltz DA. Source: Pediatric Pulmonology. 2000 September; 30(3): 198-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10973037

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Fibrosis of the upper lobes: a newly identified late-onset complication after lung transplantation? Author(s): Konen E, Weisbrod GL, Pakhale S, Chung T, Paul NS, Hutcheon MA. Source: Ajr. American Journal of Roentgenology. 2003 December; 181(6): 1539-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627569

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First lung transplant from living donors in Japan. Author(s): Asamura H. Source: Japanese Journal of Clinical Oncology. 1999 January; 29(1): 53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10073153

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First single lung transplant in Virginia. Author(s): Tribble CG, Kern JA, Findley LJ, Daniel TM, Truwit JD, Rose CE Jr, Lewis BF, Kron IL. Source: Va Med Q. 1991 Summer; 118(3): 166-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1868109

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Flow cytometric analysis of bronchoalveolar lavage and venous blood lymphocyte phenotype for the diagnosis of acute graft rejection in lung transplant patients. The Lung Transplant Group, Ospedale Maggiore di Milano. Author(s): Bonara P, Solca M, Baisi A, Bauer D, Galli A, Mocellin C, Matturri L. Source: Anal Quant Cytol Histol. 1996 August; 18(4): 293-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8862671

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Flow cytometric analysis of lung lymphocytes in lung transplant recipients. Author(s): Crim C, Keller CA, Dunphy CH, Maluf HM, Ohar JA. Source: American Journal of Respiratory and Critical Care Medicine. 1996 March; 153(3): 1041-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8630543

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Flush perfusion with low potassium dextran solution improves early graft function in clinical lung transplantation. Author(s): Struber M, Wilhelmi M, Harringer W, Niedermeyer J, Anssar M, Kunsebeck A, Schmitto JD, Haverich A. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2001 February; 19(2): 190-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167111

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Four-year follow-up of body compostion in lung transplant patients. Author(s): Kyle UG, Nicod L, Romand JA, Slosman DO, Spiliopoulos A, Pichard C. Source: Transplantation. 2003 March 27; 75(6): 821-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660509

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Four-year prospective study of pulmonary venous thrombosis after lung transplantation. Author(s): Schulman LL, Anandarangam T, Leibowitz DW, Ditullio MR, McGregor CC, Galantowicz ME, Homma S. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2001 August; 14(8): 806-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490329

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Frequency and CT findings of recurrent disease after lung transplantation. Author(s): Collins J, Hartman MJ, Warner TF, Muller NL, Kazerooni EA, McAdams HP, Slone RM, Parker LA. Source: Radiology. 2001 May; 219(2): 503-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323479

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From anti-inflammatory drugs through antifibrotic agents to lung transplantation: a long road of research, clinical attempts, and failures in the treatment of idiopathic pulmonary fibrosis. Author(s): Selman M. Source: Chest. 2002 September; 122(3): 759-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12226006

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Fungal infection in lung transplantation. Author(s): Kubak BM. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2002; 4 Suppl 3: 24-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486789

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Fungal infections in lung transplant recipients. Author(s): Bertocchi M, Thevenet F, Bastien O, Rabodonirina M, Gamondes JP, Paulus S, Loire R, Piens MA, Celard M, Mornex JF. Source: Transplantation Proceedings. 1995 April; 27(2): 1695. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7725458

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Fungal infections in lung transplantation. Incidence, risk factors and prognostic significance. Author(s): Ruffini E, Baldi S, Rapellino M, Cavallo A, Parola A, Robbiano F, Cappello N, Mancuso M. Source: Sarcoidosis Vasc Diffuse Lung Dis. 2001 June; 18(2): 181-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11436539

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Fungal wound infection in a lung transplant recipient. Author(s): Levi M, Basgoz N. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2000 March; 2(1): 36-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11429009

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Gastroesophageal reflux as a reversible cause of allograft dysfunction after lung transplantation. Author(s): Palmer SM, Miralles AP, Howell DN, Brazer SR, Tapson VF, Davis RD. Source: Chest. 2000 October; 118(4): 1214-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035701

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Gastroesophageal reflux disease in lung transplant recipients. Author(s): Hadjiliadis D, Duane Davis R, Steele MP, Messier RH, Lau CL, Eubanks SS, Palmer SM. Source: Clinical Transplantation. 2003 August; 17(4): 363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868994

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Gastrointestinal complications in lung transplant survivors that require surgical intervention. Author(s): Hoekstra HJ, Hawkins K, de Boer WJ, Rottier K, van der Bij W. Source: The British Journal of Surgery. 2001 March; 88(3): 433-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11260112

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Gastroparesis after combined heart and lung transplantation. Author(s): Sodhi SS, Guo JP, Maurer AH, O'Brien G, Srinivasan R, Parkman HP. Source: Journal of Clinical Gastroenterology. 2002 January; 34(1): 34-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743243

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Gastroparesis after lung transplantation. Potential role in postoperative respiratory complications. Author(s): Berkowitz N, Schulman LL, McGregor C, Markowitz D. Source: Chest. 1995 December; 108(6): 1602-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7497768

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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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Gene therapy in lung transplantation: feasibility of ex vivo adenovirus-mediated gene transfer to the graft. Author(s): Chapelier A, Danel C, Mazmanian M, Bacha EA, Sellak H, Gilbert MA, Herve P, Lemarchand P. Source: Human Gene Therapy. 1996 October 1; 7(15): 1837-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8894675

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Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Author(s): Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV. Source: Transplantation. 1998 October 27; 66(8): 1014-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9808485

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GI complications after lung transplantation in patients with cystic fibrosis. Author(s): Gilljam M, Chaparro C, Tullis E, Chan C, Keshavjee S, Hutcheon M. Source: Chest. 2003 January; 123(1): 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12527600

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GI complications after orthotopic lung transplantation. Author(s): Lubetkin EI, Lipson DA, Palevsky HI, Kotloff R, Morris J, Berry GT, Tino G, Rosato EF, Berlin JA, Wurster AB, Kaiser LR, Lichtenstein GR. Source: The American Journal of Gastroenterology. 1996 November; 91(11): 2382-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8931422

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Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in orthotopic lung transplant patients. Author(s): Lipson DA, Berlin JA, Palevsky HI, Kotloff RM, Tino G, Bavaria J, Kaiser L, Long WB, Metz DC, Lichtenstein GR. Source: Digestive Diseases and Sciences. 1998 June; 43(6): 1177-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635604

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Gianturco self-expanding metallic stents in treatment of tracheobronchial stenosis after single lung and heart and lung transplantation. Author(s): Spatenka J, Khaghani A, Irving JD, Theodoropoulos S, Slavik Z, Yacoub MH. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1991; 5(12): 648-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1772681

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Glomerular disease and lung transplantation. Author(s): Paller MS, Cahill B, Harmon KR, Miller RB, Sinaiko AR, Burke B, Manivel JC. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1995 September; 26(3): 527-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7645564

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Graded balloon dilation atrial septostomy as a bridge to lung transplantation in pulmonary hypertension. Author(s): Rothman A, Beltran D, Kriett JM, Smith C, Wolf P, Jamieson SW. Source: American Heart Journal. 1993 June; 125(6): 1763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8498321

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Graft eosinophilia in lung transplantation. Author(s): Yousem SA. Source: Human Pathology. 1992 October; 23(10): 1172-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1398645

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Graft failure caused by pulmonary venous obstruction diagnosed by intraoperative transesophageal echocardiography during lung transplantation. Author(s): Huang YC, Cheng YJ, Lin YH, Wang MJ, Tsai SK. Source: Anesthesia and Analgesia. 2000 September; 91(3): 558-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10960375

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Graft position and pulmonary function after single lung transplantation for obstructive lung disease. Author(s): Levine SM, Anzueto A, Gibbons WJ, Calhoon JH, Jenkinson SG, Trinkle JK, Bryan CL. Source: Chest. 1993 February; 103(2): 444-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8432134

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Graft-versus-host disease in lung transplantation: 4 case reports and literature review. Author(s): Luckraz H, Zagolin M, McNeil K, Wallwork J. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 June; 22(6): 691-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821167

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Haemolytic anaemia after lung transplantation: an immune-mediated phenomenon? Author(s): Riechsteiner G, Speich R, Schanz U, Russi EW, Weder W, Boehler A. 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 March 8; 133(9-10): 143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707841

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Have we met the expectations of heart and lung transplantation in children? Author(s): Huddleston CB. Source: Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2003; 6: 164-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740783

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HCMV DNA detection and quantitation in the plasma and PBL of lung transplant recipients: COBAS Amplicor HCMV monitor test versus in-house quantitative HCMV PCR. Author(s): Michaelides A, Facey D, Spelman D, Wesselingh S, Kotsimbos T. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 October; 28(2): 111-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957181

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Health locus of control and adherence with home spirometry use in lung transplant recipients. Author(s): Lindgren BR, Snyder M, Sabati N, Adam T, Pieczkiewicz D, Finkelstein SM. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2002 March; 12(1): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11993066

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Health-related quality of life in lung transplant candidates and recipients. Author(s): Stavem K, Bjortuft O, Lund MB, Kongshaug K, Geiran O, Boe J. Source: Respiration; International Review of Thoracic Diseases. 2000; 67(2): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10773787

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Heart transplant (HT) and heart lung transplant (HLT) in cystic fibroses (CF) patients (an overview). Author(s): Kulczycki LL. Source: Mater Med Pol. 1990 July-September; 22(3): 153-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2132420

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Heme-oxygenase-1 expression correlates with severity of acute cellular rejection in lung transplantation. Author(s): Bonnell MR, Visner GA, Zander DS, Mandalapu S, Kazemfar K, Spears L, Beaver TM. Source: Journal of the American College of Surgeons. 2004 June; 198(6): 945-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15194077

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Hemodynamics during inhaled nitric oxide in lung transplant candidates. Author(s): Della Rocca G, Pugliese F, Antonini M, Coccia C, Pompei L, Vizza CD, Rendina EA, Ricci C, Cortesini R. Source: Transplantation Proceedings. 1997 December; 29(8): 3367-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9414751

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Hepatitis C virus infection and lung transplantation: a survey of practices. Author(s): Cotler SJ, Jensen DM, Kesten S. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1999 May; 18(5): 456-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10363690

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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 dose rate brachytherapy in the management of lung transplant airway stenosis. Author(s): Halkos ME, Godette KD, Lawrence EC, Miller JI Jr. Source: The Annals of Thoracic Surgery. 2003 August; 76(2): 381-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902069

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High dose rate brachytherapy to prevent recurrent benign hyperplasia in lung transplant bronchi: theoretical and clinical considerations. Author(s): Kennedy AS, Sonett JR, Orens JB, King K. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 February; 19(2): 155-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703691

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High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. Author(s): Limaye AP, Raghu G, Koelle DM, Ferrenberg J, Huang ML, Boeckh M. Source: The Journal of Infectious Diseases. 2002 January 1; 185(1): 20-7. Epub 2001 December 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756977

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High-dose hepatitis B vaccine in patients waiting for lung transplantation. Author(s): Hayney MS, Welter DL, Reynolds AM, Francois M, Love RB. Source: Pharmacotherapy. 2003 May; 23(5): 555-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741428

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Home monitoring for lung transplant candidates. Author(s): Mullan B, Snyder M, Lindgren B, Finkelstein SM, Hertz MI. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2003 September; 13(3): 176-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14558631

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Human cytomegalovirus double resistance in a donor-positive/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response. Author(s): Baldanti F, Lilleri D, Campanini G, Comolli G, Ridolfo AL, Rusconi S, Gerna G. Source: The Journal of Antimicrobial Chemotherapy. 2004 March; 53(3): 536-9. Epub 2004 January 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739146

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Human cytomegalovirus pp67 mRNAemia versus pp65 antigenemia for guiding preemptive therapy in heart and lung transplant recipients: a prospective, randomized, controlled, open-label trial. Author(s): Gerna G, Baldanti F, Lilleri D, Parea M, Torsellini M, Castiglioni B, Vitulo P, Pellegrini C, Vigano M, Grossi P, Revello MG. Source: Transplantation. 2003 April 15; 75(7): 1012-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698090

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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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Hyperpolarized 3He-enhanced MR imaging of lung transplant recipients: preliminary results. Author(s): McAdams HP, Palmer SM, Donnelly LF, Charles HC, Tapson VF, MacFall JR. Source: Ajr. American Journal of Roentgenology. 1999 October; 173(4): 955-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10511156

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Hypogammaglobulinemia in lung transplant recipients. Author(s): Goldfarb NS, Avery RK, Goormastic M, Mehta AC, Schilz R, Smedira N, Pien L, Haug MT, Gordon SM, Hague LK, Dresing JM, Evans-Walker T, Maurer JR. Source: Transplantation. 2001 January 27; 71(2): 242-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213067

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ICU admission of the lung transplant recipient following hospital discharge. Author(s): Massad MG, Kpodonu J, Jaffe HA. Source: Chest. 2004 March; 125(3): 813-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006935

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Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMVseropositive lung transplant recipients. Author(s): Kruger RM, Paranjothi S, Storch GA, Lynch JP, Trulock EP. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 July; 22(7): 754-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873543

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Impaired antigen-presenting cell function contributes to T-cell hyporesponsiveness in stable lung transplant recipients. Author(s): Knoop C, Ismaili J, Bulte F, Abramowicz D, Estenne M, Goldman M. Source: Transplantation. 2000 April 15; 69(7): 1332-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10798749

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Incidence of clinically unsuspected pulmonary embolism in mechanically ventilated lung transplant recipients. Author(s): Burns KE, Iacono AT. Source: Transplantation. 2003 September 27; 76(6): 964-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508362

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Increased alveolar macrophage nuclear factor-kappa B activation and macrophage inhibitory protein-1alpha levels in lung transplant patients. Author(s): Farver CF, Raychaudhuri B, Malur A, Drazba J, Maurer J, Tubbs R, Mehta AC, Schilz R, Thomassen MJ. Source: Transplantation. 2000 December 15; 70(11): 1599-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11152221

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Increased endothelin-1 associated with bacterial infection in lung transplant recipients. Author(s): Charpin JM, Stern M, Lebrun G, Aubin P, Grenet D, Israel-Biet D. Source: Transplantation. 2001 June 27; 71(12): 1840-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11455267

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Increased soluble CD14 in bronchoalveolar lavage fluid of stable lung transplant recipients. Author(s): Ward C, Walters EH, Zheng L, Whitford H, Williams TJ, Snell GI. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 March; 19(3): 472-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936525

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Indications for lung transplant referral: physician attitudes. Author(s): Studer SM, Krishnan JA, Orens JB. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 June; 21(6): 716-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12057710

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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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Indirect fluorescent antibody testing of nasopharyngeal swabs for influenza diagnosis in lung transplant recipients. Author(s): Hopkins PM, Plit ML, Carter IW, Chhajed PN, Malouf MA, Glanville AR. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 February; 22(2): 161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581764

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Induced sputum cell profiles in lung transplant recipients with or without chronic rejection: correlation with lung function. Author(s): Beeh KM, Kornmann O, Lill J, Buhl R. Source: Thorax. 2001 July; 56(7): 557-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11413355

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Infectious pulmonary complications in lung transplant recipients. Author(s): Chan KM, Allen SA. Source: Seminars in Respiratory Infections. 2002 December; 17(4): 291-302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12497546

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Influence of panel-reactive antibodies on posttransplant outcomes in lung transplant recipients. Author(s): Lau CL, Palmer SM, Posther KE, Howell DN, Reinsmoen NL, Massey HT, Tapson VF, Jaggers JJ, D'Amico TA, Davis RD Jr. Source: The Annals of Thoracic Surgery. 2000 May; 69(5): 1520-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881834

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Influence of the donor lung on development of early infections in lung transplant recipients. Author(s): Zenati M, Dowling RD, Dummer JS, Paradis IL, Arena VC, Armitage JM, Kormos RL, Hardesty RL, Griffith BP. Source: J Heart Transplant. 1990 September-October; 9(5): 502-8; Discussion 508-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2231088

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Influenza and parainfluenza respiratory viral infection requiring admission in adult lung transplant recipients. Author(s): Vilchez R, McCurry K, Dauber J, Iacono A, Keenan R, Griffith B, Kusne S. Source: Transplantation. 2002 April 15; 73(7): 1075-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11965034

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Influenza pneumonia in lung transplant recipients: clinical features and association with bronchiolitis obliterans syndrome. Author(s): Garantziotis S, Howell DN, McAdams HP, Davis RD, Henshaw NG, Palmer SM. Source: Chest. 2001 April; 119(4): 1277-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296201

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Intensive cardiopulmonary support for otherwise dying post-heart and lung transplant recipients with extracorporeal membrane oxygenation. Author(s): Lee CJ. Source: Artificial Organs. 2001 August; 25(8): 597-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11531707

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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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Invasive fungal sinusitis caused by Scytalidium dimidiatum in a lung transplant recipient. Author(s): Dunn JJ, Wolfe MJ, Trachtenberg J, Kriesel JD, Orlandi RR, Carroll KC. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5817-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662991

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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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Kaposi's sarcoma after lung transplantation in a Sephardic Jewish woman. Author(s): Kantor R, Mayan H, Shalmon B, Reichert N, Farfel Z. Source: Dermatology (Basel, Switzerland). 2000; 200(1): 49-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10681615

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Laparoscopic antireflux surgery in the lung transplant population. Author(s): Lau CL, Palmer SM, Howell DN, McMahon R, Hadjiliadis D, Gaca J, Pappas TN, Davis RD, Eubanks S. Source: Surgical Endoscopy. 2002 December; 16(12): 1674-8. Epub 2002 July 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140642

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Laparoscopic Nissen fundoplication for treating reflux in lung transplant recipients. Author(s): O'Halloran EK, Reynolds JD, Lau CL, Manson RJ, Davis RD, Palmer SM, Pappas TN, Clary EM, Eubanks WS. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2004 January; 8(1): 132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14746846

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Legionellosis in a lung transplant recipient obscured by cytomegalovirus infection and Clostridium difficile colitis. Author(s): Nichols L, Strollo DC, Kusne S. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2002 March; 4(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12123425

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Living donor lung transplantation: selection, technique, and outcome. Author(s): Barr ML, Baker CJ, Schenkel FA, Bowdish ME, Bremner RM, Cohen RG, Barbers RG, Woo MS, Horn MV, Wells WJ, Starnes VA. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3527-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750504

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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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Lobar transplantation, split lung transplantation and peripheral segmental resection-reliable procedures for downsizing donor lungs. Author(s): Aigner C, Mazhar S, Jaksch P, Seebacher G, Taghavi S, Marta G, Wisser W, Klepetko W. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2004 February; 25(2): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747109

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Long term outcome of lung transplant is predicted by the number of HLA-DR mismatches. Author(s): Nizami IY. Source: Transplantation. 2002 February 27; 73(4): 668. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889453

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Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients. Author(s): Burkart GJ, Smaldone GC, Eldon MA, Venkataramanan R, Dauber J, Zeevi A, McCurry K, McKaveney TP, Corcoran TE, Griffith BP, Iacono AT. Source: Pharmaceutical Research. 2003 February; 20(2): 252-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636164

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Lung infections in pediatric lung transplantation: experience in 49 cases. Author(s): Metras D, Viard L, Kreitmann B, Riberi A, Pannetier-Mille A, Garbi O, Marti JY, Geigle P. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1999 April; 15(4): 490-4; Discussion 495. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371127

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Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group. Author(s): Muller C, Furst H, Reichenspurner H, Briegel J, Groh J, Reichart B. Source: Transplantation. 1999 October 27; 68(8): 1139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10551643

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Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience. Author(s): Heath JA, Kurland G, Spray TL, Kernan NA, Small TN, Brochstein JA, Gillio AP, Boklan J, O'Reilly RJ, Boulad F. Source: Transplantation. 2001 December 27; 72(12): 1986-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773900

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Lung transplantation for pulmonary vascular disease. Author(s): Mendeloff EN, Meyers BF, Sundt TM, Guthrie TJ, Sweet SC, de L, Shapiro S, Balzer DT, Trulock EP, Lynch JP, Pasque MK, Cooper JD, Huddleston CB, Patterson GA. Source: The Annals of Thoracic Surgery. 2002 January; 73(1): 209-17; Discussion 217-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834012

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Management of acute hypoxemia during flexible bronchoscopy with insertion of a nasopharyngeal tube in lung transplant recipients. Author(s): Chhajed PN, Aboyoun C, Malouf MA, Hopkins PM, Plit M, Grunstein RR, Glanville AR. Source: Chest. 2002 April; 121(4): 1350-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948074

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Management of biliary tract disease in heart and lung transplant patients. Author(s): Gupta D, Sakorafas GH, McGregor CG, Harmsen WS, Farnell MB. Source: Surgery. 2000 October; 128(4): 641-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11015098

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Management of lung transplant recipients with bronchogenic carcinoma in the native lung. Author(s): de Perrot M, Fischer S, Waddell TK, Strueber M, Harringer W, Pierre AF, Spiliopoulos A, Haverich A, Keshavjee S. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 January; 22(1): 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531417

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Medical complications of lung transplantation. Author(s): Kotloff RM, Ahya VN. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2004 February; 23(2): 334-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14979513

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Microangiopathic haemolytic anaemia and thrombocytopenia following lung volume reduction surgery in a single lung transplant recipient on maintenance tacrolimus (FK506) therapy. Author(s): Reid DW, Street A, Mansfield D, Chin W, Cole-Sinclair M, Williams TJ, Snell GI. Source: Respirology (Carlton, Vic.). 2003 June; 8(2): 243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753543

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Mother to child: first living donor lung transplant. Author(s): Goldsmith MF. Source: Jama : the Journal of the American Medical Association. 1990 December 5; 264(21): 2724. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2232048

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MRI in lung transplant recipients using hyperpolarized 3He: comparison with CT. Author(s): Gast KK, Viallon M, Eberle B, Lill J, Puderbach MU, Hanke AT, Schmiedeskamp J, Kauczor HU. Source: Journal of Magnetic Resonance Imaging : Jmri. 2002 March; 15(3): 268-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11891971

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Multidrug-resistant tuberculosis in a lung transplant recipient. Author(s): Lee J, Yew WW, Wong CF, Wong PC, Chiu CS. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 October; 22(10): 1168-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550827

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Mycobacterium abscessus empyema in a lung transplant recipient. Author(s): Fairhurst RM, Kubak BM, Shpiner RB, Levine MS, Pegues DA, Ardehali A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 March; 21(3): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897529

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Mycobacterium marinum infection in a lung transplant recipient. Author(s): Torres F, Hodges T, Zamora MR. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 April; 20(4): 486-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295588

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Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. Author(s): Monforte V, Roman A, Gavalda J, Bravo C, Tenorio L, Ferrer A, Maestre J, Morell F. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 December; 20(12): 1274-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744410

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Neosynthesized IgG detected by Western blotting in Toxoplasma-seropositive heart or lung transplant recipients. Author(s): Robert-Gangneux F, Amrein C, Lavarde V, Botterel F, Dupouy-Camet J. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2000; 13(6): 448-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11140244

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Neuropsychological dysfunction in patients with end-stage pulmonary disease: lung transplant evaluation. Author(s): Crews WD Jr, Jefferson AL, Broshek DK, Rhodes RD, Williamson J, Brazil AM, Barth JT, Robbins MK. Source: Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists. 2003 May; 18(4): 353-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14591451

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New immunosuppressive drugs and lung transplantation: last or least? Author(s): van den Berg JW, Postma DS, Koeter GH, van der Bij W. Source: Thorax. 1999 June; 54(6): 550-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10335012

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New telemetric system for daily pulmonary function surveillance of lung transplant recipients. Author(s): Wagner FM, Weber A, Park JW, Schiemanck S, Tugtekin SM, Gulielmos V, Schuler S. Source: The Annals of Thoracic Surgery. 1999 December; 68(6): 2033-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10616972

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NO: more than just a vasodilator in lung transplantation. Author(s): Karamsetty MR, Klinger JR. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 January; 26(1): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11751196

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Nocardia infection in lung transplant recipients. Author(s): Husain S, McCurry K, Dauber J, Singh N, Kusne S. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 March; 21(3): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897524

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Novel bacterium isolated from a lung transplant patient with cystic fibrosis. Author(s): Pitulle C, Citron DM, Bochner B, Barbers R, Appleman MD. Source: Journal of Clinical Microbiology. 1999 December; 37(12): 3851-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565895

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Nutritional assessment of the lung transplant patient: body mass index as a predictor of 90-day mortality following transplantation. Author(s): Madill J, Gutierrez C, Grossman J, Allard J, Chan C, Hutcheon M, Keshavjee SH; Toronto Lung Transplant Program. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 March; 20(3): 288-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11257554

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Nutritional status, ICU duration and ICU mortality in lung transplant recipients. Author(s): Plochl W, Pezawas L, Artemiou O, Grimm M, Klepetko W, Hiesmayr M. Source: Intensive Care Medicine. 1996 November; 22(11): 1179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9120110

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Obliterative bronchiolitis in the lung transplant recipient. A powerful foe. Author(s): Smith-Seiler DA, Iacono AT. Source: Adv Nurse Pract. 2004 April; 12(4): 69-74. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101139

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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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Optimizing lung transplant immunosuppression: beyond calcineurin inhibition. Author(s): Mulligan MS, Wood DE. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 April; 125(4): 784-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698139

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Orthotopic lung transplant for sarcoidosis. Author(s): Egan TM. Source: Chest. 2003 March; 123(3): 962-3; Author Reply 963. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12628907

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Osteoporosis before lung transplantation: association with low body mass index, but not with underlying disease. Author(s): Tschopp O, Boehler A, Speich R, Weder W, Seifert B, Russi EW, Schmid C. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2002 February; 2(2): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099519

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Outcome improving for lung transplant patients. Author(s): McCarthy PM. Source: Cleve Clin J Med. 1990 November-December; 57(8): 673-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2257673

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Outcome of lung transplant patients admitted to the medical ICU. Author(s): Hadjiliadis D, Steele MP, Govert JA, Davis RD, Palmer SM. Source: Chest. 2004 March; 125(3): 1040-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006966

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Outcome of lung transplantation in patients with mycetomas. Author(s): Hadjiliadis D, Sporn TA, Perfect JR, Tapson VF, Davis RD, Palmer SM. Source: Chest. 2002 January; 121(1): 128-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796441

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Outcome of the native lung after single lung transplant. Multiorgan Transplant Group. Author(s): Frost AE, Keller CA, Noon GP, Short HD, Cagle PT. Source: Chest. 1995 April; 107(4): 981-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7705165

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Outcomes for patients with sarcoidosis awaiting lung transplantation. Author(s): Shorr AF, Davies DB, Nathan SD. Source: Chest. 2002 July; 122(1): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114364

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Pleural effusions in lung transplant recipients: image-guided small-bore catheter drainage. Author(s): Marom EM, Palmer SM, Erasmus JJ, Herndon JE, Zhang C, McAdams HP. Source: Radiology. 2003 July; 228(1): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832585

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Positron emission tomography with fluoro-2-deoxy-D-glucose (FDG-PET) in the staging of post transplant lymphoproliferative disorder in lung transplant recipients. Author(s): Marom EM, McAdams HP, Butnor KJ, Coleman RE. Source: Journal of Thoracic Imaging. 2004 April; 19(2): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15071322

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Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients. Author(s): Reams BD, McAdams HP, Howell DN, Steele MP, Davis RD, Palmer SM. Source: Chest. 2003 October; 124(4): 1242-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555552

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Predictors of lung transplant survival in eurotransplant. Author(s): Smits JM, Mertens BJ, Van Houwelingen HC, Haverich A, Persijn GG, Laufer G. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 November; 3(11): 1400-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525601

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Pre-emptive therapy with azoles in lung transplant patients. Geneva Lung Transplantation Group. Author(s): Hamacher J, Spiliopoulos A, Kurt AM, Nicod LP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1999 January; 13(1): 180-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10836345

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Pregnancy in lung transplant recipients. Author(s): Gertner G, Coscia L, McGrory C, Moritz M, Armenti V. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2000 June; 10(2): 109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933764

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Primary cutaneous cryptococcosis in a lung transplant recipient. Author(s): Baumgarten KL, Valentine VG, Garcia-Diaz JB. Source: Southern Medical Journal. 2004 July; 97(7): 692-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15301128

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Progressive multifocal leukoencephalopathy in a lung transplant recipient. Author(s): Shitrit D, Nirit L, Shiran SI, Izbicki G, Sofer D, Eldad M, Kramer MR. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 August; 22(8): 946-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909477

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Psychological functioning and quality of life in lung transplant candidates and recipients. Author(s): Limbos MM, Joyce DP, Chan CK, Kesten S. Source: Chest. 2000 August; 118(2): 408-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936133

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Pulmonary nodules in lung transplant recipients: etiology and outcome. Author(s): Lee P, Minai OA, Mehta AC, DeCamp MM, Murthy S. Source: Chest. 2004 January; 125(1): 165-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718437

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Quality of life before and after lung transplantation in patients with emphysema versus other indications. Author(s): TenVergert EM, Vermeulen KM, Geertsma A, van Enckevort PJ, de Boer WJ, van der Bij W, Koeter GH. Source: Psychological Reports. 2001 December; 89(3): 707-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824741

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Quality of life in female lung transplant candidates and recipients. Author(s): Limbos MM, Chan CK, Kesten S. Source: Chest. 1997 November 5; 112(5): 1165-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9367452

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Quality of life in patients awaiting lung transplant: cystic fibrosis versus other endstage lung diseases. Author(s): Burker EJ, Carels RA, Thompson LF, Rodgers L, Egan T. Source: Pediatric Pulmonology. 2000 December; 30(6): 453-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109056

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Quality of life in pediatric heart, heart-lung, and lung transplant recipients. Author(s): Nixon PA, Morris KA. Source: International Journal of Sports Medicine. 2000 November; 21 Suppl 2: S109-11; Discussion S112. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11142595

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Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients. Author(s): Bhorade SM, Sandesara C, Garrity ER, Vigneswaran WT, Norwick L, Alkan S, Husain AN, McCabe MA, Yeldandi V. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 September; 20(9): 928-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557186

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Quantification of cytomegalovirus DNA in BAL fluid: a longitudinal study in lung transplant recipients. Author(s): Riise GC, Andersson R, Bergstrom T, Lundmark A, Nilsson FN, Olofsson S. Source: Chest. 2000 December; 118(6): 1653-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115455

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Quantitative analysis of cytomegalovirus viremia in lung transplant recipients. Author(s): Bailey TC, Buller RS, Ettinger NA, Trulock EP, Gaudreault-Keener M, Langlois TM, Fornoff JE, Cooper JD, Storch GA. Source: The Journal of Infectious Diseases. 1995 April; 171(4): 1006-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7706777

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Quantitative cultures of the cell fraction and supernatant of bronchoalveolar lavage fluid for the diagnosis of cytomegalovirus pneumonitis in lung transplant recipients. Author(s): Storch GA, Ettinger NA, Ockner D, Wick MR, Gaudreault-Keener M, Rossiter J, Trulock EP, Cooper JD. Source: The Journal of Infectious Diseases. 1993 December; 168(6): 1502-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8245535

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Quantitative detection of human cytomegalovirus DNA in lung transplant recipients. Author(s): Kotsimbos AT, Sinickas V, Glare EM, Esmore DS, Snell GI, Walters EH, Williams TJ. Source: American Journal of Respiratory and Critical Care Medicine. 1997 October; 156(4 Pt 1): 1241-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9351628

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Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease. Author(s): Verschuuren E, van der Bij W, de Boer W, Timens W, Middeldorp J, The TH. Source: Journal of Medical Virology. 2003 February; 69(2): 258-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12683416

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Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: correlation with transplant outcome. Author(s): Meloni F, Vitulo P, Bianco AM, Paschetto E, Morosini M, Cascina A, Mazzucchelli I, Ciardelli L, Oggionni T, Fietta AM, Pozzi E, Vigano M. Source: Transplantation. 2004 March 15; 77(5): 762-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15021844

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Relationship of cytomegalovirus viral load in blood to pneumonitis in lung transplant recipients. Author(s): Sanchez JL, Kruger RM, Paranjothi S, Trulock EP, Lynch JP, Hicks C, Shannon WD, Storch GA. Source: Transplantation. 2001 August 27; 72(4): 733-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11544440

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Research on the quality of life of lung transplant candidates and recipients: an integrative review. Author(s): Lanuza DM, Lefaiver CA, Farcas GA. Source: Heart & Lung : the Journal of Critical Care. 2000 May-June; 29(3): 180-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819800

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Resistance training prevents vertebral osteoporosis in lung transplant recipients. Author(s): Mitchell MJ, Baz MA, Fulton MN, Lisor CF, Braith RW. Source: Transplantation. 2003 August 15; 76(3): 557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923444

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Respiratory viruses and chronic rejection in lung transplant recipients. Author(s): Billings JL, Hertz MI, Savik K, Wendt CH. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 May; 21(5): 559-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983546

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Results of an artificial-lung survey to lung transplant program directors. Author(s): Haft JW, Griffith BP, Hirschl RB, Bartlett RH. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 April; 21(4): 467-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927224

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Reversal of nocturnal periodic breathing in primary pulmonary hypertension after lung transplantation. Author(s): Schulz R, Fegbeutel C, Olschewski H, Rose F, Schafers HJ, Seeger W. Source: Chest. 2004 January; 125(1): 344-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718466

84

Lung Transplant

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Risk factors and management of bleeding associated with transbronchial lung biopsy in lung transplant recipients. Author(s): Chhajed PN, Aboyoun C, Malouf MA, Hopkins PM, Plit ML, Glanville AR. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 February; 22(2): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581769

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Risk quantification of early outcome after lung transplantation: donor, recipient, operative, and post-transplant parameters. Author(s): Sekine Y, Waddell TK, Matte-Martyn A, Pierre AF, de Perrot M, Fischer S, Marshall J, Granton J, Hutcheon MA, Keshavjee S. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2004 January; 23(1): 96-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734133

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Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection. Author(s): Sumpter TL, Wilkes DS. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2004 June; 286(6): L1129-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15136293

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Safety of aerosolized amphotericin B lipid complex in lung transplant recipients. Author(s): Palmer SM, Drew RH, Whitehouse JD, Tapson VF, Davis RD, McConnell RR, Kanj SS, Perfect JR. Source: Transplantation. 2001 August 15; 72(3): 545-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502995

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Scedosporium apiospermum fungemia in a lung transplant recipient. Author(s): Raj R, Frost AE. Source: Chest. 2002 May; 121(5): 1714-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006471

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Severe axonal polyneuropathy after a FK506 overdosage in a lung transplant recipient. Author(s): Boukriche Y, Brugiere O, Castier Y, Stocco J, Mal H, Fournier M. Source: Transplantation. 2001 December 15; 72(11): 1849-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740402

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Severe Ehrlichia chaffeensis infection in a lung transplant recipient: a review of ehrlichiosis in the immunocompromised patient. Author(s): Safdar N, Love RB, Maki DG. Source: Emerging Infectious Diseases. 2002 March; 8(3): 320-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927032

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Sputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients: relation to tumor necrosis factor-alpha and interleukin-10. Author(s): Beeh KM, Beier J, Kornmann O, Micke P, Buhl R. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 November; 20(11): 1144-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704473

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Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients. Author(s): Dransfield MT, Garver RI, Weill D. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2004 January; 23(1): 110-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734135

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Subcutaneous phaeohyphomycotic cysts caused by Exophiala jeanselmei in a lung transplant patient. Author(s): Xu X, Low DW, Palevsky HI, Elenitsas R. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 April; 27(4): 343-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298703

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Successful conversion from cyclosporine to tacrolimus for gastric motor dysfunction in a lung transplant recipient. Author(s): Verleden GM, Besse T, Maes B. Source: Transplantation. 2002 June 27; 73(12): 1974-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131703

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Successful pregnancy outcome in a lung transplant recipient with tacrolimus immunosuppression. A case report. Author(s): Kruszka SJ, Gherman RB. Source: J Reprod Med. 2002 January; 47(1): 60-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838314

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Surgery in heart and lung transplant patients. Author(s): Velanovich V, Ezzat W, Horn C, Bernabei A. Source: American Journal of Surgery. 2004 April; 187(4): 501-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041499

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Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism. Author(s): Zheng H, Zeevi A, Schuetz E, Lamba J, McCurry K, Griffith BP, Webber S, Ristich J, Dauber J, Iacono A, Grgurich W, Zaldonis D, McDade K, Zhang J, Burckart GJ. Source: Journal of Clinical Pharmacology. 2004 February; 44(2): 135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747421

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Tacrolimus-induced hemolytic uremic syndrome case presentation in a lung transplant recipient. Author(s): Shitrit D, Starobin D, Aravot D, Fink G, Izbicki G, Kramer M. Source: Transplantation Proceedings. 2003 March; 35(2): 627-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644073

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Ten years of lung transplantation in Switzerland: results of the Swiss Lung Transplant Registry. Author(s): Speich R, Nicod LP, Aubert JD, Spiliopoulos A, Wellinger J, Robert JH, Stocker R, Zalunardo M, Gasche-Soccal P, Boehler A, Weder W. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2004 January 10; 134(1-2): 18-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745663

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The first lung transplant. Author(s): Dalton ML. Source: The American Surgeon. 2004 April; 70(4): 364-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15098793

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The presence of a local lung transplant center increases lung procurement rates. Author(s): McVicar JP, Albertson TE, Troppmann C, Kappes J, Perez RV. Source: Transplantation. 2003 June 27; 75(12): 2128-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829923

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The value of polymerase chain reaction for the diagnosis of viral respiratory tract infections in lung transplant recipients. Author(s): Weinberg A, Zamora MR, Li S, Torres F, Hodges TN. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2002 August; 25(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12367651

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Tolerability, safety and efficacy of conventional amphotericin B administered by 24hour infusion to lung transplant recipients. Author(s): Speich R, Dutly A, Naef R, Russi EW, Weder W, Boehler A. 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 August 10; 132(31-32): 455-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457304

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Transforming growth factor-beta1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line. Munich Lung Transplant Group. Author(s): Jaumann F, Elssner A, Mazur G, Dobmann S, Vogelmeier C. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 June; 15(6): 1052-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10885424

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Transfusion-related acute lung injury (Trali) in a patient with a single lung transplant. Author(s): Dykes A, Smallwood D, Kotsimbos T, Street A. Source: British Journal of Haematology. 2000 June; 109(3): 674-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10886228

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Two case reports: fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient. Author(s): Mattner F, Weissbrodt H, Strueber M. Source: Scandinavian Journal of Infectious Diseases. 2004; 36(4): 312-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15198193

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Ultraflex stents for the management of airway complications in lung transplant recipients. Author(s): Chhajed PN, Malouf MA, Tamm M, Glanville AR. Source: Respirology (Carlton, Vic.). 2003 March; 8(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856743

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Unilateral auto-PEEP in the recipient of a single lung transplant. Author(s): Popple C, Higgins TL, McCarthy P, Baldyga A, Mehta A. Source: Chest. 1993 January; 103(1): 297-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8417907

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Update on cystic fibrosis: selected aspects related to lung transplantation. Author(s): Boehler A. 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 February 22; 133(7-8): 111-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644957

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Use of 18FDG-pet to discriminate between infection and rejection in lung transplant recipients. Author(s): Jones HA, Donovan T, Goddard MJ, McNeil K, Atkinson C, Clark JC, White JF, Chilvers ER. Source: Transplantation. 2004 May 15; 77(9): 1462-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15167609

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Use of cytomegalovirus (CMV) hyperimmune globulin for prevention of CMV disease in CMV-seropositive lung transplant recipients. Author(s): Zamora MR, Fullerton DA, Campbell DN, Leone S, Diercks MJ, Fisher JH, Badesch DB, Grover FL. Source: Transplantation Proceedings. 1994 October; 26(5 Suppl 1): 49-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7940974

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Use of lung biopsies in lung transplant recipients. Author(s): Scott JP, Higenbottam TW, Smyth RL, McGoldrick JP, Wallwork J. Source: Transplantation. 1990 January; 49(1): 234. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2301020

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Using conceptual triangulation to develop an integrated model of the symptom experience of acute rejection after lung transplantation. Author(s): De Vito Dabbs A, Hoffman LA, Swigart V, Happ MB, Iacono AT, Dauber JH. Source: Ans. Advances in Nursing Science. 2004 April-June; 27(2): 138-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15206685

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Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Medical College of Wisconsin Lung Transplant Group. Author(s): Tan RT, Kuzo R, Goodman LR, Siegel R, Haasler GB, Presberg KW. Source: Chest. 1998 May; 113(5): 1250-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9596302

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Utility of inhaled pentamidine prophylaxis in lung transplant recipients. Author(s): Nathan SD, Ross DJ, Zakowski P, Kass RM, Koerner SK. Source: Chest. 1994 February; 105(2): 417-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8306738

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Valaciclovir for chronic hepatitis B virus infection after lung transplantation. Author(s): Laube I, Boehler A, Renner EL, Speich R. Source: Infection. 2004 February; 32(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15007743

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Validity of standard gamble utilities as measured by transplant readiness in lung transplant candidates. Author(s): Singer LG, Theodore J, Gould MK. Source: Medical Decision Making : an International Journal of the Society for Medical Decision Making. 2003 September-October; 23(5): 435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570301

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Value of mycophenolic acid trough level monitoring after lung transplantation. Author(s): Devyatko E, Ploner M, Zuckermann A, Jaksch P, Tschernko E, Klepetko W, Wisser W. Source: Transplantation Proceedings. 2002 August; 34(5): 1881-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176612

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Variability in standard care for cytomegalovirus prevention and detection in pediatric lung transplantation: survey of eight pediatric lung transplant programs. Author(s): Danziger-Isakov LA, Faro A, Sweet S, Michaels MG, Aurora P, Mogayzel PJ Jr, Mallory GB Jr, Boyer DM, Rice TB, DelaMorena M, DeBaun MR; International Pediatric Lung Transplant Collaborative Group. Source: Pediatric Transplantation. 2003 December; 7(6): 469-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14870896

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Vascular endothelial growth factor in human lung transplantation. Author(s): Meyer KC, Cardoni AL, Xiang Z, Cornwell RD, Love RB. Source: Chest. 2001 January; 119(1): 137-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157595

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Video-assisted minimally invasive approach in clinical bilateral lung transplantation. Author(s): Fischer S, Struber M, Simon AR, Anssar M, Wilhelmi M, Leyh RG, Harringer W, Haverich A. Source: The Journal of Thoracic and Cardiovascular Surgery. 2001 December; 122(6): 1196-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726896

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Videothoracoscopic wedge resection of the lung for the diagnosis of acute rejection in lung transplant recipients. Author(s): Hoffmann H, Bittmann I, Moroder E, Reichenspurner H, Dienemann H. Source: Transplantation Proceedings. 1995 June; 27(3): 2002-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792866

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Visceral leishmaniasis in lung transplantation. Author(s): Morales P, Torres JJ, Salavert M, Peman J, Lacruz J, Sole A. Source: Transplantation Proceedings. 2003 August; 35(5): 2001-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962876

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Visual symptoms after lung transplantation: a case of progressive multifocal leukoencephalopathy. Author(s): Ouwens JP, Haaxma-Reiche H, Verschuuren EA, Timens W, Steenhuis LH, de Boer WJ, van der Bij W; Groningen Lung Transplant Group. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2000 March; 2(1): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11429007

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Volumetric monitoring in multiorgan donor and related lung transplant recipients. Author(s): Della Rocca G, Passariello M, Costa MG, Coccia C, Pompei L, Pierconti F, Venuta F, De Giacomo T, Pietropaoli P, Cortesini R. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1637-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267452

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Waiting for lung transplantation: family experiences of relocation. Author(s): Stubblefield C, Murray RL. Source: Pediatric Nursing. 2002 September-October; 28(5): 501-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424986

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Waiting to make the weight for lung transplantation. Author(s): Levine SM, Sako EY. Source: Chest. 2002 February; 121(2): 317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834634

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Weight gain after lung transplantation. Author(s): Singer LG, Brazelton TR, Doyle RL, Morris RE, Theodore J; International Lung Transplant Database Study Group. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 August; 22(8): 894-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909470

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What is the role of surfactant and inhaled nitric oxide in lung transplantation? Author(s): Struber M. Source: Critical Care (London, England). 2002 June; 6(3): 186-7. Epub 2002 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133173

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What is your diagnosis? Multiple unilateral nodular pulmonary lesions in a lung transplant recipient. Diagnosis: focal intrapulmonary hemorrhage following transbronchial lung biopsy. Author(s): Laube I, Hauser M, Thurnheer R, Gaspert A, Schmid RA, Weder W, Speich R. Source: Respiration; International Review of Thoracic Diseases. 1999; 66(1): 91-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973701

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When is lung transplantation appropriate? Author(s): Egan TM. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1992 September-October; 11(5): 1008. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1420229

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Which patients are candidates for lung transplantation? Indications for unilateral, bilateral, and heart-lung procedures. Author(s): Ettinger NA. Source: J Crit Illn. 1994 January; 9(1): 38-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10146649

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Who waits longest for heart and lung transplantation? Author(s): Sharples L, Belcher C, Dennis C, Higenbottam T, Wallwork J. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1994 March-April; 13(2): 282-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8031813

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Wrapping the anastomosis with omentum or an internal mammary artery pedicle does not improve bronchial healing after single lung transplantation: results of a randomized clinical trial. Author(s): Khaghani A, Tadjkarimi S, al-Kattan K, Banner N, Daly R, Theodoropoulos S, Madden B, Yacoub M. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1994 September-October; 13(5): 767-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7803416

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Yield of surveillance transbronchial biopsies performed beyond two years after lung transplantation. Author(s): Kesten S, Chamberlain D, Maurer J. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1996 April; 15(4): 384-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732597

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CHAPTER 2. NUTRITION AND LUNG TRANSPLANT Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and lung transplant.

Finding Nutrition Studies on Lung Transplant 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 “lung transplant” (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 “lung transplant” (or a synonym): •

5-HT2-mediated bronchial responses after syngeneic lung transplantation in the rat. Author(s): Laboratoire de physiologie respiratoire, UFR Cochin-Port-Royal, Paris. Source: Tavakoli, R Frossard, N Br-J-Pharmacol. 1995 April; 114(7): 1428-32 0007-1188

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Adaptation of a weight management program for a potential lung transplant candidate. Author(s): Jewish Hospital, Louisville, Ky., USA. Source: Forsythe, J Cooley, K Greaver, B Prog-Transplant. 2000 December; 10(4): 234-8 1526-9248

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Amelioration of reperfusion injury by pentoxifylline after lung transplantation. The Universite Paris-Sud Lung Transplant Group. Author(s): Laboratoire de Chirurgie Experimentale, Hopital Marie Lannelongue, Universite Paris Sud, Le Plessis Robinson, France. Source: Chapelier, A Reignier, J Mazmanian, M Dulmet, E Libert, J M Dartevelle, P Barbotin, F Herve, P J-Heart-Lung-Transplant. 1995 Jul-August; 14(4): 676-83 1053-2498

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Assessment of airway tone in asthma. Comparison between double lung transplant patients and healthy subjects. Author(s): Department of Medicine, University of Toronto, Ontario, Canada. Source: Molfino, N A Slutsky, A S Julia Serda, G Hoffstein, V Szalai, J P Chapman, K R Rebuck, A S Zamel, N Am-Rev-Respir-Dis. 1993 November; 148(5): 1238-43 0003-0805

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Butylated hydroxytoluene and N-acetylcysteine attenuates tumor necrosis factoralpha (TNF-alpha) secretion and TNF-alpha mRNA expression in alveolar macrophages from human lung transplant recipients in vitro. Author(s): Wallenberg Laboratory, Sahlgrenska University Hospital, Goteborg, Sweden. [email protected] Source: Hulten, L M Lindmark, H Schersten, H Wiklund, O Nilsson, F N Riise, G C Transplantation. 1998 August 15; 66(3): 364-9 0041-1337

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Cardiac innervation after double lung transplantation. Toronto Lung Transplant Group. Author(s): Division of Thoracic Surgery, Toronto General Hospital, Ontario, Canada. Source: Schaefers, H J Waxman, M B Patterson, G A Frost, A E Maurer, J Cooper, J D JThorac-Cardiovasc-Surg. 1990 January; 99(1): 22-9 0022-5223

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Compromised antioxidant status and persistent oxidative stress in lung transplant recipients. Author(s): Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK. Source: Williams, A Riise, G C Anderson, B A Kjellstrom, C Schersten, H Kelly, F J FreeRadic-Res. 1999 May; 30(5): 383-93 1071-5762

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Donor treatment with the lazeroid U74389G reduces ischemia-reperfusion injury in a rat lung transplant model. Author(s): Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany. Source: Hausen, B Mueller, P Bahra, M Ramsamooj, R Morris, R E Hewitt, C W AnnThorac-Surg. 1997 September; 64(3): 814-20 0003-4975

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L-arginine and pentoxifylline attenuate endothelial dysfunction after lung reperfusion injury in the rabbit. The Paris-Sud University Lung Transplant Group. Author(s): Laboratoire de Chirurgie Experimentale, Unite de Recherche Associee 1159, Paris-Sud University, Le Plessis Robinson, France. Source: Normandin, L Herve, P Brink, C Chapelier, A R Dartevelle, P G Mazmanian, G M Ann-Thorac-Surg. 1995 September; 60(3): 646-50 0003-4975

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Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplant model. Author(s): Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8556. Source: Kuwaki, K Komatsu, K Sohma, H Abe, T Ann-Thorac-Cardiovasc-Surg. 1999 February; 5(1): 11-7 1341-1098

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Lung preservation with Euro-Collins, University of Wisconsin, Wallwork, and lowpotassium-dextran solution. Universite++ Paris-Sud Lung Transplant Group. Author(s): Centre Chirurgical Marie Lannelongue, Universite Paris Sud, Le Plessis Robinson, France. Source: Xiong, L Mazmanian, M Chapelier, A R Reignier, J Weiss, M Dartevelle, P G Herve, P Ann-Thorac-Surg. 1994 September; 58(3): 845-50 0003-4975

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Metallothionein expression in human lung and its varying levels after lung transplantation. Toulouse Lung Transplantation Group. Author(s): Service d'Histologie-Cytologie du Pr Caratero, CHU Rangueil, Toulouse, France. Source: Courtade, M Carrera, G Paternain, J L Martel, S Carre, P C Folch, J Pipy, B Chest. 1998 February; 113(2): 371-8 0012-3692

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Mitogen responses of lymphocytes from lung transplant recipients--correlation with rejection and infection. Author(s): Division of Cardiothoracic Surgery, University of Pittsburgh, Pennsylvania 15261. Source: Keenan, R J Uknis, M E Pham, S M Spichty, K Duquesnoy, R J Griffith, B P Zeevi, A Transplantation. 1992 August; 54(2): 241-5 0041-1337

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Nutrition support for lung transplant patients. Source: Holcombe, B J Resler, R Nutr-Clin-Pract. 1994 December; 9(6): 235-9 0884-5336

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Pentoxifylline and lung ischemia-reperfusion injury: application to lung transplantation. Universite Paris-Sud Lung Transplant Group. Author(s): Laboratoire de Chirurgie Experimentale, Hopital Marie Lannelongue, Universite Paris Sud, France. Source: Chapelier, A Reignier, J Mazmanian, M Detruit, H Dartevelle, P Parquin, F Cerrina, J Le Roy Ladurie, F Herve, P J-Cardiovasc-Pharmacol. 1995; 25 Suppl 2S130-3 0160-2446

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Pharmacokinetic assessment of oral ganciclovir in lung transplant recipients with cystic fibrosis. Author(s): Lung and Heart Transplant Service, Departments of Clinical Pharmacology, Pharmacy and Clinical Biochemistry, Alfred Hospital, Prahran 3181, Australia. Source: Snell, G I Kotsimbos, T C Levvey, B J Skiba, M Rutherford, D M Kong, D C Williams, T J Krum, H J-Antimicrob-Chemother. 2000 April; 45(4): 511-6 0305-7453

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Salvage therapy with mycophenolate mofetil for lung transplant bronchiolitis obliterans: importance of dosage. Author(s): Department of Internal Medicine, University Hospital Zurich, Switzerland. [email protected] Source: Speich, R Boehler, A Thurnheer, R Weder, W Transplantation. 1997 August 15; 64(3): 533-5 0041-1337

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Single lung transplantation for canine pulmonary hypertension. Author(s): Department of Surgery, Kobe University School of Medicine, Chuo-ku, Japan. Source: Okada, M Yamashita, C Okada, M Nohara, H Yamagishi, H Wakiyama, H Okada, K J-Heart-Lung-Transplant. 1997 May; 16(5): 532-7 1053-2498

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Survival and graft function in a large animal lung transplant model after 30 h preservation and substitution of the nitric oxide pathway. Author(s): Division of General Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland. Source: Hillinger, S Sandera, P Carboni, G L Stammberger, U Zalunardo, M Schoedon, G Schmid, R A Eur-J-Cardiothorac-Surg. 2001 September; 20(3): 508-13 1010-7940

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Transient left ventricular failure following bilateral lung transplantation for pulmonary hypertension. Author(s): Department of Cardiothoracic Surgery, University of Vienna, Austria. Source: Birsan, T Kranz, A Mares, P Artemiou, O Taghavi, S Zuckermann, A Klepetko, W J-Heart-Lung-Transplant. 1999 April; 18(4): 304-9 1053-2498

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Use of complementary therapies, adherence, and quality of life in lung transplant recipients. Author(s): Minnesota State University Moorhead, 56563, USA. Source: Matthees, B J Anantachoti, P Kreitzer, M J Savik, K Hertz, M I Gross, C R HeartLung. 2001 Jul-August; 30(4): 258-68 0147-9563

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. ALTERNATIVE MEDICINE AND LUNG TRANSPLANT Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to lung transplant. 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 lung transplant 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 “lung transplant” (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 lung transplant: •

A disciplined approach to spiritual care giving for adults living with cystic fibrosis. Author(s): Palmer C. Source: Journal of Health Care Chaplaincy. 2001; 11(1): 95-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11398539

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Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr-virusassociated lymphoma. Author(s): Mentzer SJ, Fingeroth J, Reilly JJ, Perrine SP, Faller DV. Source: Blood Cells, Molecules & Diseases. 1998 June; 24(2): 114-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9628848

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Assessment and management of psychosocial stress in lung transplant candidates. Toronto Lung Transplant Group. Author(s): Bright MJ, Craven JL, Kelly PJ. Source: Health & Social Work. 1990 May; 15(2): 125-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2365238

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Autologous lymphokine-activated killer cell therapy of lymphoproliferative disorders arising in organ transplant recipients. Author(s): Nalesnik MA, Rao AS, Zeevi A, Fung JJ, Pham S, Furukawa H, Gritsch A, Klein G, Starzl TE. Source: Transplantation Proceedings. 1997 May; 29(3): 1905-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9142315

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Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate. Author(s): Trombetti A, Gerbase MW, Spiliopoulos A, Slosman DO, Nicod LP, Rizzoli R. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 August; 19(8): 736-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10967266

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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

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Cardiac innervation after double lung transplantation. Toronto Lung Transplant Group. Author(s): Schaefers HJ, Waxman MB, Patterson GA, Frost AE, Maurer J, Cooper JD. Source: The Journal of Thoracic and Cardiovascular Surgery. 1990 January; 99(1): 22-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2294361

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Challenging issues associated with organ transplantation for Jehovah's Witness individuals. Author(s): Mallory GB Jr. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 February; 19(2): 119-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703685

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Collagenolytic activity in hyperacute lung allograft rejection. Author(s): Lubec G, Moschl P, Keiler A, Szalay S. Source: Pathology, Research and Practice. 1980; 167(2-4): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6253969

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Combined radiation and chemotherapy in posttransplant lymphoproliferative disorder. Author(s): Tsai DE, Stadtmauer EA, Canaday DJ, Vaughn DJ. Source: Medical Oncology (Northwood, London, England). 1998 December; 15(4): 27981. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9951693

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Cystic fibrosis-related diabetes. Author(s): Mackie AD, Thornton SJ, Edenborough FP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 June; 20(6): 425-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786675

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Effects of a telephone-based psychosocial intervention for patients awaiting lung transplantation. Author(s): Napolitano MA, Babyak MA, Palmer S, Tapson V, Davis RD, Blumenthal JA; Investigational Study of Psychological Intervention in Recipients of Lung Transplant (INSPIRE) Investigators. Source: Chest. 2002 October; 122(4): 1176-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377839

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Evaluation of CMV viral load using TaqMan CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients. Author(s): Guiver M, Fox AJ, Mutton K, Mogulkoc N, Egan J. Source: Transplantation. 2001 June 15; 71(11): 1609-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435973

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External stimuli in the form of vibratory massage after heart or lung transplantation. Author(s): Doering TJ, Fieguth HG, Steuernagel B, Brix J, Konitzer M, Schneider B, Fischer GC. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 1999 March-April; 78(2): 108-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10088583

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Genistein inhibits constitutive and inducible NFkappaB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells. Author(s): Tabary O, Escotte S, Couetil JP, Hubert D, Dusser D, Puchelle E, Jacquot J. Source: American Journal of Pathology. 1999 August; 155(2): 473-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10433940

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Growing up with cystic fibrosis. Author(s): Helms PJ.

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Source: Br J Hosp Med. 1993 September 15-October 5; 50(6): 326-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8080484 •

Hodgkin's disease after cardiac transplant: a report of two cases. Author(s): Hood IM, Mahendra P, McNeil K, Marcus RE. Source: Clinical and Laboratory Haematology. 1996 June; 18(2): 115-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8866145

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Hydrophobic extracts of a Chinese herb (CMX-13) exhibit potent immunosuppressive properties and prevent acute rejection in a highly histoincompatible model of rat lung transplantation. Author(s): Zuo XJ, Okada Y, Toyoda M, Yap HK, Marchevsky A, Matloff JM, Jordan SC. Source: Transplantation. 2000 October 15; 70(7): 1094-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11045648

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Hypothermia and high pressure oxygen in whole organ storage. Author(s): Rudolf LE. Source: Transplantation Proceedings. 1969 September; 1(3): 795-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4939676

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Identity, role, and task: a core perspective on pastoral care with cardiothoracic transplantations. Author(s): Thorstenson T. Source: Journal of Health Care Chaplaincy. 1993; 5(1-2): 11-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10129256

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Immunosuppressive effect of the hydrophobic extract of a Chinese herb on rat lung allograft rejection. Author(s): Yap HK, Zuo XJ, Toyoda M, Okada Y, Ang SG, Lai YH, Matloff JM, Marchevsky A, Ramgolam VS, Jordan SC. Source: Transplantation Proceedings. 1998 June; 30(4): 980-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636395

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Iron chelation therapy and lung transplantation. Effects of deferoxamine on lung preservation in canine single lung transplantation. Author(s): Conte JV Jr, Katz NM, Foegh ML, Wallace RB, Ramwell PW. Source: The Journal of Thoracic and Cardiovascular Surgery. 1991 June; 101(6): 1024-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2038195

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Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation. Author(s): Bhorade SM, Vigneswaran W, McCabe MA, Garrity ER.

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Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 December; 19(12): 1199-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11124490 •

Lung transplantation in a Jehovah's witness. Case report in a twinning procedure. Author(s): Grande AM, Rinaldi M, D'Armini AM, Pellegrini C, Vigano M. Source: The Journal of Cardiovascular Surgery. 2003 February; 44(1): 131-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627085

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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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Of mind, body, and modern technology. Author(s): Anbar RD. Source: Clinical Pediatrics. 2000 July; 39(7): 433-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914310

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Pediatric thoracic organ transplants: challenges in primary care. Author(s): Teets JM, Borisuk MJ; Children's Hospital of Philadelphia. Source: Pediatric Nursing. 2004 January-February; 30(1): 23-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022848

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Preservation of the canine lung in vitro for 24 hours with the use of hypothermia and hyperbaric oxygen. Author(s): Blumenstock DA, Lempert N, Morgado F. Source: The Journal of Thoracic and Cardiovascular Surgery. 1965 December; 50(6): 76974. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5321162

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Psychosocial and financial aspects of lung transplantation. Author(s): Smolin TL, Aguiar LJ. Source: Critical Care Nursing Clinics of North America. 1996 September; 8(3): 293-303. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9095803

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Pulmonary lesions in guinea pigs and rats after subcutaneous injection of complete Freund's adjuvant or homologous pulmonary tissue. Author(s): Schiefer B, Stunzi H.

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Source: Zentralbl Veterinarmed A. 1979 January; 26(1): 1-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=106589 •

Pulmonary rehabilitation and surgery for end-stage lung disease. Author(s): Kesten S. Source: Clinics in Chest Medicine. 1997 June; 18(2): 173-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9187813

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Pulmonary rehabilitation for chronic lung disease. Author(s): Resnikoff PM, Ries AL. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1998 July; 17(7): 643-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9703227

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Pulmonary rehabilitation programs in Canada: national survey. Author(s): Brooks D, Lacasse Y, Goldstein RS. Source: Can Respir J. 1999 January-February; 6(1): 55-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10202221

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Rapid detection by reverse hybridization of mutations in the UL97 gene of human cytomegalovirus conferring resistance to ganciclovir. Author(s): Zhou L, Harder TC, Ullmann U, Rautenberg P. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 1999 June; 13(1-2): 53-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10405892

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Salvage chemotherapy for refractory or relapsed post-transplant lymphoproliferative disorder in patients after solid organ transplantation with a combination of carboplatin and etoposide. Author(s): Oertel SH, Papp-Vary M, Anagnostopoulos I, Hummel MW, Jonas S, Riess HB. Source: British Journal of Haematology. 2003 December; 123(5): 830-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632773

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Selectin-dependent rolling and adhesion of leukocytes in nicotine-exposed microvessels of lung allografts. Author(s): Sikora L, Rao SP, Sriramarao P. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 September; 285(3): L654-63. Epub 2003 June 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794008

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Standards for rehabilitative strategies in respiratory diseases. Author(s): Ambrosino N, Vitacca M, Rampulla C.

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Source: Monaldi Arch Chest Dis. 1995 August; 50(4): 293-318. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7550210 •

Successful 24-hour pulmonary preservation using hyperbaric oxygen. Author(s): Yamashita C, Oobo H, Yamamoto H, Tobe S, Koterazawa T, Nakamura H, Okada M. Source: Transplantation Proceedings. 1994 April; 26(2): 882-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8171694

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Successful transplantation of lungs topically cooled in the non-heart-beating donor for 6 hours. Author(s): Steen S, Ingemansson R, Budrikis A, Bolys R, Roscher R, Sjoberg T. Source: The Annals of Thoracic Surgery. 1997 February; 63(2): 345-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9033298

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Telesupport: just reach out and touch someone. Author(s): Nathan SD, Barnett SD. Source: Chest. 2002 October; 122(4): 1114-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377827

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Use of complementary therapies, adherence, and quality of life in lung transplant recipients. Author(s): Matthees BJ, Anantachoti P, Kreitzer MJ, Savik K, Hertz MI, Gross CR. Source: Heart & Lung : the Journal of Critical Care. 2001 July-August; 30(4): 258-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11449212

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to lung transplant; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Integrative Medicine Communications; www.drkoop.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com

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

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CHAPTER 4. PATENTS ON LUNG TRANSPLANT 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 “lung transplant” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lung transplant, we have not necessarily excluded nonmedical patents in this bibliography.

Patent Applications on Lung Transplant 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 lung transplant:

8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 9 This has been a common practice outside the United States prior to December 2000.

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Carbon monoxide as a biomarker and therapeutic agent Inventor(s): Choi, Augustine M.; (Guilford, CT), Lee, Patty J.; (Guilford, CT), Leo, Otterbein E.; (Hamden, CT) Correspondence: Janis K. Fraser, PH.D., J.D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020155166 Date filed: January 15, 2002 Abstract: The present invention relates to the use of carbon monoxide (CO) as a biomarker and therapeutic agent of heart, lung, liver, spleen, brain, skin and kidney diseases and other conditions and disease states including, for example, asthma, emphysema, bronchitis, adult respiratory distress syndrome, sepsis, cystic fibrosis, pneumonia, interstitial lung diseases, idiopathic pulmonary diseases, other lung diseases including primary pulmonary hypertension, secondary pulmonary hypertension, cancers, including lung, larynx and throat cancer, arthritis, wound healing, Parkinson's disease, Alzheimer's disease, peripheral vascular disease and pulmonary vascular thrombotic diseases such as pulmonary embolism. CO may be used to provide anti-inflammatory relief in patients suffering from oxidative stress and other conditions especially including sepsis and septic shock. In addition, carbon monoxide may be used as a biomarker or therapeutic agent for reducing respiratory distress in lung transplant patients and to reduce or inhibit oxidative stress and inflammation in transplant patients. Excerpt(s): This application claims priority from provisional application No. 60/127,616, filed Apr. 1, 1999. Heme oxygenase (HO) catalyzes the first and rate limiting step in the degradation of heme to yield equimolar quantities of biliverdin IXa, carbon monoxide (CO), and iron (Choi, et al., Am. J. Respir. Cell Mol. Biol. 15: 9-19; and Maines, Annu. Rev. Pharmacol. Toxicol. 37: 517-554). Three isoforms of HO exist; HO-1 is highly inducible while HO-2 and HO-3 are constitutively expressed (Choi, et al., supra, Maines, supra and McCoubrey, et al., E. J. Bioch. 247: 725-732). Although heme is the major substrate of HO-1, a variety of non-heme agents including heavy metals, cytokines, hormones, endotoxin and heat shock are also strong inducers of HO-1 expression (Choi, et al., supra, Maines, supra and Tenhunen, et al., J. Lab. Clin. Med. 75: 410-421). This diversity of HO-1 inducers has provided further support for the speculation that HO-1, besides its role in heme degradation, may also play a vital function in maintaining cellular homeostasis. Furthermore, HO-1 is highly induced by a variety of agents causing oxidative stress including hydrogen peroxide, glutathione depletors, UV irradiation, endotoxin and hyperoxia (Choi, et al., supra, Maines, supra and Keyse, et al., Proc. Natl. Acad. Sci. USA. 86: 99-103). One interpretation of this finding is that HO-1 can serve as a key biological molecule in the adaptation and/or defense against oxidative stress (Choi, et al., supra, Lee, et al., Proc Natl Acad Sci USA 93: 10393-10398; Otterbein, et al., Am. J. J. Respir. Cell Mol. Biol. 13: 595-601; Poss, et al., Proc. Natl. Acad. Sci. USA. 94: 10925-10930; Vile, et al., Proc. Natl. Acad. Sci. 91: 2607-2610; Abraham, et al., Proc. Natl. Acad. Sci. USA. 92: 6798-6802; and Vile and Tyrrell, J. Biol. Chem. 268: 14678-14681. Our laboratory and others have shown that induction of endogenous HO-1 provides protection both in vivo and in vitro against oxidative stress associated with hyperoxia and lipopolysaccharide-induced tissue injury (Lee, et al., supra, Otterbein, et al., supra and Taylor, et al., Am. J Physiol. 18: L582-L591). We have also shown that exogenous administration of HO-1 via gene transfer can provide protection against oxidant tissue injury and elicit tolerance to hyperoxic stress (Otterbein, et al., Am. J. Resp. Crit. Care Med. 157: A565 (Abstr)).

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

Compositions and methods for treatment of lung transplants Inventor(s): Forstner, Janet; (Toronto, CA), Keshavje, Shaf; (Toronto, CA), Sajjan, Umadevi; (Toronto, CA) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20030134773 Date filed: July 9, 2002 Abstract: Methods and compositions for pre-treatment of lung transplants to reduce susceptibility to post-operative B. cepacia infection are provided. The methods and compositions employ saccharides, particularly dextrans and xylitol, which are applied to the lung transplant before transplantation. Excerpt(s): The present invention relates to therapies for treating lung pathogen infection in humans, and more particularly, to compositions and methods for pretreating lung transplants prior to transplantation. Chronic bronchopulmonary infections are the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Pseudomonas aeruginosa is the predominant respiratory tract pathogen in patients with cystic fibrosis leading to progressive pulmonary deterioration. Treatments utilizing polysaccharides for the treatment of P. aeruginosa infection in CF patients have been suggested but are not yet in general use. In vitro experiments have shown that dextran can inhibit the adherence of P. aeruginosa to epithelial cells (Barghouthi et al, Am. J. Respir. Crit. Care Med. 1996, 154:1788-1793) and that xylitol has antimicrobial effects on coagulase negative staphyloccus (Zabner et al., PNAS, 2000, 97:11614-11619). U.S. Pat. No. 5,441,938 is directed to the use of D-glucose or D-mannose in the treatment or prevention by P. aeruginosa in cystic fibrosis patients. U.S. Pat. No. 5,514,665 is directed to methods and compositions using the polysaccharides dextran sulfate or dextran for the treatment of P. aeruginosa infection in vivo in compromised hosts such as cystic fibrosis patients. Polyols such as xylitol have also been used in methods of treating S. pneumoniae respiratory infections as is disclosed in U.S. Pat. Nos. 5,719,196, 6,066,677 and 6,143,330. Although Pseudomonas aeruginosa is the major opportunistic respiratory pathogen isolated from CF patients, a subgroup of these patients (3-5% globally) also becomes infected with Burkholderia cepacia which is a particularly infectious bacterial species that is resistant to killing by standard antimicrobial preparations. In North America, the prevalence is about 8-10% and is much higher in the certain clinics such as the Toronto adult CF clinic (46%). The clinical outcome of B. cepacia-infected patients is unpredictable and varies widely, from no adverse effects to fatal necrotizing pneumonia within a few months of infection (cepacia syndrome) or after being colonized for several years. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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USE OF AEROSOLIZED CYCLOSPORINE FOR PREVENTION AND TREATMENT OF PULMONARY DISEASE Inventor(s): IACONO, ALDO T.; (PITTSBURGH, PA) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20020006901 Date filed: February 5, 1999 Excerpt(s): The present invention relates to methods and compositions for prevention of graft rejection in lung transplant recipients and for treatment of subjects with pulmonary disorders. Specifically, the methods and compositions of the invention provide a means for inhibiting immune response mediated inflammatory processes in the lungs. The method of the invention comprises the administration of aerosolized cyclosporine for prevention of acute and/or chronic refractory rejection in lung transplant patients. The invention is based on the observation that when aerosolized cyclosporine is administered shortly after lung transplantation, the preparation is well tolerated and the rate of acute rejection is substantially reduced, compared to controls that receive conventional oral or intravenous immunosuppression only. The invention further provides for the use of aerosolized cyclosporine to treat subjects having immunologically mediated inflammatory pulmonary disorders including, but not limited to, asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic bronchitis and allergic rhinitis. The present invention, by enabling a method for the use of aerosolized cyclosporine for inhibiting pulmonary inflammation leading to prevention of graft rejection and treatment of pulmonary disorders, provides a safer and less toxic treatment than those methods that utilize systemic administration of cyclosporine. The long-term success of lung transplantation is currently limited by the high incidence of transplant-related lung disease (Glanville, A. R., et al., 1987, Ann Intern Med 107:300306; Trulock, E. P., 1993, Chest 103:1566-1576; Kesten, S., 1995, 152: 1321-1324; Paradis, I. et al., 1993, 14:751-763). This complication is related to the transplant recipients' ongoing immune response against donor major histocompatability antigens. Such an immune response generally leads to persistent acute rejection of the lung allograft which is a predominant risk factor for the subsequent development of chronic rejection and permanent allograft dysfunction and failure resulting in excessive morbidity and mortality. This is a tragic consequence of lung transplantation and for this reason, is a leading area of research in this field. Although the rates of short-term survival after lung transplantation have improved compared to most other solid organ transplants, the therapeutic benefit of lung transplantation is still limited by poor longer-term outcomes principally due to chronic rejection of the transplanted lung. Patients, whose lung allografts are in acute and/or chronic rejection, are currently treated by a variety of potent immunosuppressive agents, such as azathioprine, tacrolimus, mycophenolate mofetil and cyclosporine, generally given by the intravenous or oral route, that profoundly inhibit the T cell response to donor antigen within the transplanted allograft. Unfortunately, these immunosuppressive agents diminish the patient's ability to mount an effective response to viral, fungal and bacterial pathogens thereby predisposing the patient to life threatening opportunistic infections and other toxic events such as kidney toxicity. Despite usage of conventional systemic (oral or intravenous) immunosuppressive drugs, about 50% of the treated patients develop refractory chronic rejection, characterized histologically by bronchiolitis obliterans, followed by a progressive decline in pulmonary function and eventually respiratory failure and death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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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, 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 lung transplant, 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 “lung transplant” (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 lung transplant. You can also use this procedure to view pending patent applications concerning lung transplant. 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 5. BOOKS ON LUNG TRANSPLANT Overview This chapter provides bibliographic book references relating to lung transplant. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lung transplant include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “lung transplant” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on lung transplant: •

Comprehensive Guide to Transplant Nutrition Source: Chicago, IL: American Dietetic Association. 2002. 264 p. Contact: Available from American Dietetic Association. 120 South Riverside Plaza, Chicago, IL 60606-6695. (800) 877-1600, ext. 5000. Fax (312) 899-4899. E-mail: [email protected]. Website: www.eatright.org. PRICE: $40.50 for members; $53.00 for nonmembers. ISBN: 88091193X. Summary: This book offers practical nutrition guidelines for adult and pediatric organ and hematopoietic stem cell transplantation (HSCT) patients. The authors are experts in the field of transplant nutrition and are from highly recognized transplant centers. Each chapter provides comprehensive guidelines on how to assess patients, nutrient requirements for acute and chronic posttransplant phases, feeding modalities, and nutrition therapy for potential transplant-related complications. The text reviews theory

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and comprehensive advice and highlights critical short term and long term nutrition recommendations in tables. The book includes 12 chapters: overview and immunosuppression; adult heart and lung transplantation; adult kidney transplantation; adult liver transplantation; adult pancreas transplantation; adult small bowel transplantation; adult HSCT; pediatric lung transplantation; pediatric kidney transplantation; pediatric liver transplantation; pediatric small bowel transplantation; and pediatric HSCT. Each chapter concludes with references and the book concludes with a subject index.

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

Solid Organ Transplantation Source: in Gottschlich, M.M.; Matarese, L.E.; Shronts, E.P., eds. Nutrition Support Dietetics. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition. 1993. p. 409-421. Contact: Available from American Society for Parenteral and Enteral Nutrition. 8630 Fenton Street, Suite 412, Silver Spring, MD 20910. (301) 587-6315. PRICE: $40 plus $5 shipping/handling for members; $60 plus $7 shipping/handling for nonmembers. Summary: This chapter, from a book of nutrition support dietetics, summarizes recommendations for patients undergoing solid organ transplantation. Written in outline form, the chapter covers the typical diagnosis for solid organ transplantation; nutrition assessment considerations, including anthropometrics, laboratory tests, other objective tests, the role of the complete nutrition history, and physical examination; estimating short-term nutritional needs, including calorie, protein, carbohydrate, fat, vitamin, electrolyte, mineral, and fluid needs; estimating long-term nutritional needs; nutrition support for liver transplant, renal transplant (primarily oral diet considerations, heart and/or lung transplants, and pancreas transplant; and monitoring nutrition support. The article concludes with a self-assessment posttest. 3 tables. 56 references.

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CHAPTER 6. PERIODICALS AND NEWS ON LUNG TRANSPLANT Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lung transplant.

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

African Americans fare worse after lung transplantation for sarcoidosis Source: Reuters Medical News Date: March 25, 2004

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Pulmonary nodules not uncommon in lung transplant recipients Source: Reuters Medical News Date: February 06, 2004

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Chiron licenses inhalable lung transplant rejection drug from Novartis Source: Reuters Industry Breifing Date: April 22, 2003

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Early screening for Aspergillus warranted in CF lung transplant recipients Source: Reuters Medical News Date: March 27, 2003

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Wyeth repeats Rapamune lung transplant warning in US Source: Reuters Industry Breifing Date: February 21, 2003

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Wyeth warns of sirolimus safety issues in lung transplant patients Source: Reuters Industry Breifing Date: February 12, 2003

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New lung transplant method could multiply organ availability Source: Reuters Medical News Date: March 15, 2001

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Aspergillus tracheobronchitis in lung transplant recipients warrants aggressive treatment Source: Reuters Medical News Date: March 12, 2001

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Potency of immunosuppression after lung transplantation cannot be reduced Source: Reuters Medical News Date: September 06, 2000

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Aerosol cyclosporine hinders P-glycoprotein activity in lung transplant patients Source: Reuters Medical News Date: August 29, 2000

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Pros and cons of single versus double lung transplantation debated Source: Reuters Medical News Date: May 16, 2000

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Pulmonary hemodynamics may indicate priority for lung transplantation in CF patients Source: Reuters Medical News Date: April 25, 2000

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Annexin V shows promise for imaging acute lung transplant rejection Source: Reuters Medical News Date: March 30, 2000

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Double lung transplantation unnecessary for patients with secondary pulmonary hypertension Source: Reuters Medical News Date: March 23, 2000

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NOS gene transfer reduces reperfusion injury in lung transplant model Source: Reuters Medical News Date: February 23, 2000

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Donor BMT with heart and lung transplants reduces rejection rate Source: Reuters Medical News Date: April 26, 1999

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Nitric oxide treatment benefits lung transplant patients Source: Reuters Medical News Date: February 01, 1999

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “lung transplant” (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 “lung transplant” (or synonyms). If you know the name of a company that is relevant to lung transplant, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “lung transplant” (or synonyms).

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

Friendly Fire: Lifesaving Cyclosporine Takes Toll on Kidneys Source: UNOS Update. p. 18-20. Summer 1997. Contact: Available from United Network for Organ Sharing. 1100 Boulders Parkway, Suite 500, P.O. Box 13770, Richmond, VA 23225-8770. (888) 894-6361 or (804) 330-8541. Summary: This newsletter article describes the effects of cyclosporine, an immunosuppressive agent, on the kidneys. As transplant recipients are living longer, and thus receiving the drug for prolonged periods, cyclosporine-induced kidney damage has become a growing challenge. Researchers are now exploring explore ways to fight this potentially life-threatening condition. The long term effects of cyclosporine may cause some transplant patients without any prior kidney disease, particularly those receiving heart, liver, and lung transplants, to require dialysis or kidney transplantation. The article briefly reports on a research study that demonstrated that treatment with cyclosporine for more than 12 to 24 months can cause progressive injury to the kidney that is rarely reversible. The author then outlines the factors that play a role in the development of cyclosporine-induced kidney damage. The article notes a number of measures to help identify or delay the progress of kidney damage. Among the most important is earlier referral to a transplant nephrologist. Other suggested safety measures include a low protein diet, good blood pressure control, and the use of ACE inhibitors, when appropriate. 2 figures.

Academic Periodicals covering Lung Transplant Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lung transplant. In addition to these sources, you can search for articles covering lung transplant that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.”

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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 7. 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 lung transplant. 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).

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to lung transplant by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “lung transplant” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for lung transplant: •

Technetiurm Tc99m rh-Annexin V (trade name: Apomate) http://www.rarediseases.org/nord/search/nodd_full?code=1076

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

•

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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.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 “lung transplant” (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 7416 86 808 75 35 8420

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 “lung transplant” (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 lung transplant 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 lung transplant. 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 lung transplant. 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 “lung transplant”:

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Heart Transplantation http://www.nlm.nih.gov/medlineplus/hearttransplantation.html Islet Cell Transplantation http://www.nlm.nih.gov/medlineplus/isletcelltransplantation.html Liver Transplantation http://www.nlm.nih.gov/medlineplus/livertransplantation.html Lung Transplantation http://www.nlm.nih.gov/medlineplus/lungtransplantation.html Organ Transplantation http://www.nlm.nih.gov/medlineplus/organtransplantation.html Pancreas Transplantation http://www.nlm.nih.gov/medlineplus/pancreastransplantation.html

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

Organizations Division of Transplantation Source: Health Resources and Services Administration http://www.hrsa.gov/osp/dot/dotmain.htm National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ Scientific Registry of Transplant Recipients http://www.ustransplant.org/

•

Statistics Fast Facts about Transplants Source: Scientific Registry of Transplant Recipients http://www.ustransplant.org/csr_0704/facts.php Lung Center Data Profile Source: Organ Procurement and Transplantation Network http://www.optn.org/organDatasource/stateData.asp?type=state&mqsd=1&displ ay=Lung Organ Facts: Lung Source: United Network for Organ Sharing http://www.transplantliving.org/OrganFacts/lung.aspx

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.

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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 lung transplant. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Associations and Lung Transplant The following is a list of associations that provide information on and resources relating to lung transplant: •

Second Wind Lung Transplant Association, Inc Telephone: (727) 442-0892 Toll-free: (888) 855-9463 Fax: (727) 442-9762 Email: [email protected] Web Site: http://www.2ndwind.org Background: Second Wind Lung Transplant Association, Inc. is a not-for-profit organization dedicated to improving the quality of life for lung transplant recipients, lung surgery candidates, people with related pulmonary concerns, and their families. The Association provides support, advocacy, education, information, and guidance through a spirit of service, 'adding years to their lives and life to their years.' Established in 1995 by a group of lung transplant recipients, candidates, and their families, Second Wind has quarterly support group meetings to provide educational programs (e.g., on nutrition, effects of medications and exercise, physical therapy) for both lung transplant candidates and recipients; to share experiences; and to enjoy social activities. In addition, the organization provides educational programs; seeks to increase Organ

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Donor Awareness; and provides a quarterly newsletter entitled 'AirWays' to its members.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lung transplant. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lung transplant. 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 lung transplant. 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 “lung transplant” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “lung transplant”. 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 “lung transplant” (or synonyms) into the “For

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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 “lung transplant” (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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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/

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

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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 lung transplant: •

Basic Guidelines for Lung Transplant Lung transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003010.htm

•

Signs & Symptoms for Lung Transplant Lung disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000066.htm Problems breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm

•

Background Topics for Lung Transplant Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm

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Immune response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.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

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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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LUNG TRANSPLANT 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] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH]

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Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjustment Disorders: Maladaptive reactions to identifiable psychosocial stressors occurring within a short time after onset of the stressor. They are manifested by either impairment in social or occupational functioning or by symptoms (depression, anxiety, etc.) that are in excess of a normal and expected reaction to the stressor. [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] 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] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [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] 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] Air Embolism: Occurs when the lungs over expand to the point that air bubbles are forced through the air sacs of the lungs into the circulatory system. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when

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their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] 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] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH] Alpha 1-Antitrypsin Deficiency: A disease caused by single gene defects. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of

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pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] 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] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] 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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] 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] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

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

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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] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [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-infective: An agent that so acts. [EU] 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH]

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Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artificial Eye: Usually made of artificial plastic material or glass to which small quantities of metallic oxides have been added in order to imitate the features and coloring of the various parts of t he human eye; a prosthesis made of glass, plastic, or similar material. [NIH] Artificial Limbs: Prosthetic replacements for arms, legs, and parts therof. [NIH] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed

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from a person, stored, and then given back to the person after intensive treatment. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Balloon dilation: A treatment for benign prostatic hyperplasia or prostate enlargement. A tiny balloon is inflated inside the urethra to make it wider so urine can flow more freely from the bladder. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [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. 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [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]

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Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH]

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Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [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] 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] 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] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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 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

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many enzymatic processes. [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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [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] 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]

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Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and 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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological

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processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] 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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [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] 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] 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] 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

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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] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] 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] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH]

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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] 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] 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] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [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] 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

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anticancer drugs. [NIH] 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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a 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] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes.

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[NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4+ Tlymphocytes. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. [NIH] Dextrans: A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietetics: The study and regulation of the diet. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense

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mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] 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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ehrlichiosis: A tick-borne disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In humans the disease is caused by Ehrlichia chaffeensis, in dogs it is caused by E. canis, and in horses, E. equi. [NIH] 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]

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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] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [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] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

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] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH]

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Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [NIH] Enzyme Repression: The interference in synthesis of an enzyme due to the elevated level of an effector substance, usually a metabolite, whose presence would cause depression of the gene responsible for enzyme synthesis. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

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] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of

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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 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 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] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin;

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another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [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 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] Forced Expiratory Volume: Measure of the maximum amount of air during a forced vital capacity determination that can be expelled in a given number of seconds. It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity. [NIH] Forearm: The part between the elbow and the wrist. [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] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some

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reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] 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 Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [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

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participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [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] Granule: A small pill made from sucrose. [EU] 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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [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

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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] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart- Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH]

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Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [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] 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] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [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 bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain

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hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH] 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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Imbedding: The implantation of the fertilized ovum in the endometrium of the pregnant uterus. [NIH]

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Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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

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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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In 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 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] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been

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identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-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-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-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] 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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH]

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Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

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] Isolated lung perfusion: A surgical procedure during which the circulation of blood to the lungs is separated from the circulation of blood through the rest of the body, and a drug is delivered directly into the lung circulation. This allows a higher concentration of chemotherapy to reach tumors in the lungs. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH]

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Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Living Donors: Non-cadaveric providers of organs for transplant to related or non-related recipients. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH]

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Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] 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] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic

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moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes 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] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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 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] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts

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in the presence of ultraviolet A irradiation. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] 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] 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]

Minor Histocompatibility Loci: Genetic loci responsible for the encoding of histocompatibility antigens other than those encoded by the major histocompatibility complex. The antigens encoded by these genes are often responsible for graft rejection in cases where histocompatibility has been established by standard tests. The location of some of these loci on the X and Y chromosomes explains why grafts from males to females may be rejected while grafts from females to males are accepted. In the mouse roughly 30 minor histocompatibility loci have been recognized, comprising more than 500 genes. [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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other

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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] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [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] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] 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] 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]

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 Mucosa: The mucous membrane lining the nasal cavity. [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] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] 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

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nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutrition Assessment: Evaluation and measurement of nutritional variables in order to assess the level of nutrition or the nutritional status of the individual. Nutrition surveys may be used in making the assessment. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [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] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH]

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Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic cup: The white, cup-like area in the center of the optic disc. [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] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [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] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH]

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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] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pastoral Care: Counseling or comfort given by ministers, priests, rabbis, etc., to those in need of help with emotional problems or stressful situations. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pedicle: Embryonic link between the optic vesicle or optic cup and the forebrain or diencephalon, which becomes the optic nerve. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [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

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vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] 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] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH]

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Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] 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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] 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]

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] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA

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or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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

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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] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostheses and Implants: Artificial substitutes for body parts, and materials inserted into tissue for functional, cosmetic, or therapeutic purposes. Prostheses can be functional, as in the case of artificial arms and legs, or cosmetic, as in the case of an artificial eye. Implants, all surgically inserted or grafted into the body, tend to be used therapeutically. Experimental implants is available for those used experimentally. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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]

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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] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [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]

Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a

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thin fluid called liquor puris). [EU] 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] 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] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] Reactivation: The restoration of activity to something that has been inactivated. [EU] 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]

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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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [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] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Repressor Proteins: Proteins which are normally bound to the operator locus of an operon, thereby preventing transcription of the structural genes. In enzyme induction, the substrate of the inducible enzyme binds to the repressor protein, causing its release from the operator and freeing the structural genes for transcription. In enzyme repression, the end product of the enzyme sequence binds to the free repressor protein, the resulting complex then binds to the operator and prevents transcription of the structural genes. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which

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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 distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] 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] 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] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] 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.

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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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH]

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Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sil: The arithmetical average of the octave band sound pressure levels of a noise, centered on the frequencies 425, 850 and 1700 Hz together with the frequency 212 of the SIL in this band exceeds the others by 10 dB or more. [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] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [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 graft: Skin that is moved from one part of the body to another. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [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]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] Spasmogenic: Capable of producing convulsions. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH]

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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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] 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, 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] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] 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]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [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] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] 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]

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Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] 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 of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [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]

Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Systemic: Affecting the entire body. [NIH]

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Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] 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] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] 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] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] 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]

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Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transplantation Tolerance: An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response. [NIH]

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Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [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] 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] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]

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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] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viremia: The presence of viruses in the blood. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vital Capacity: The volume of air that is exhaled by a maximal expiration following a maximal inspiration. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voriconazole: A drug that treats infections caused by fungi. [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]

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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] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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, 147, 185, 186 Aberrant, 8, 147 Ablation, 39, 147 Abortion, 147, 189 Acceptor, 147, 177, 184 Acetylcholine, 147, 157, 182, 183 Acetylcysteine, 94, 147 Acrylonitrile, 147, 193 Actin, 147, 182 Acute Disease, 52, 147 Acute renal, 46, 147, 170 Adaptability, 147, 156, 157 Adaptation, 94, 108, 147 Adenine, 147 Adenosine, 34, 147, 186 Adenovirus, 65, 148 Adjustment, 16, 40, 57, 147, 148 Adjustment Disorders, 40, 148 Adjuvant, 103, 148 Adoptive Transfer, 41, 148 Adrenal Cortex, 148, 160, 189 Adverse Effect, 109, 148, 195 Aerobic, 38, 148 Aerosol, 20, 29, 33, 46, 116, 148 Affinity, 42, 148 Agonist, 148, 183 Air Embolism, 49, 148 Air Sacs, 148, 149 Airway, 8, 9, 12, 16, 17, 21, 25, 30, 42, 43, 49, 54, 58, 68, 85, 87, 94, 148, 155 Albumin, 148, 184 Algorithms, 13, 149, 154 Alkaloid, 149, 183 Allergic Rhinitis, 110, 149, 169 Allo, 12, 17, 20, 30, 149 Allogeneic, 6, 8, 11, 17, 33, 75, 149, 169, 170 Alpha 1-Antitrypsin, 5, 149 Alpha 1-Antitrypsin Deficiency, 5, 149 Alpha Particles, 149, 191 Alternative medicine, 117, 149 Alveoli, 149, 201 Amino acid, 149, 150, 152, 161, 168, 172, 185, 186, 188, 189, 190, 193, 197, 199, 200 Amino Acid Sequence, 149, 150, 168 Amplification, 44, 57, 149 Anaemia, 46, 66, 76, 149

Anaesthesia, 149, 174 Anal, 62, 150, 178 Analog, 150, 168 Anaphylatoxins, 24, 150, 159 Anastomosis, 91, 150 Anatomical, 150, 152, 160, 174, 194 Androgens, 148, 150, 160 Anesthesia, 60, 66, 148, 150 Angiogenesis, 22, 150 Angiogram, 31, 150 Animal model, 6, 9, 10, 12, 18, 19, 26, 29, 39, 150 Annealing, 150, 188 Anomalies, 150, 181 Anorexia, 150, 163 Antagonism, 6, 150 Antiallergic, 150, 160 Antibiotic, 150, 167, 185 Antibodies, 6, 11, 30, 56, 71, 150, 152, 169, 173, 178, 181, 187 Antibody, 10, 18, 20, 24, 37, 55, 71, 148, 150, 151, 158, 159, 165, 169, 171, 173, 174, 176, 179, 181, 191, 194, 196, 202 Anticoagulant, 151, 162, 190 Antifungal, 33, 151, 176, 195 Antigen-Antibody Complex, 151, 159 Antigen-presenting cell, 18, 70, 151, 161 Anti-infective, 151, 172 Anti-inflammatory, 14, 63, 108, 151, 160, 169, 189 Anti-Inflammatory Agents, 151, 160 Antimetabolite, 151, 193 Antimicrobial, 69, 109, 151, 157 Antineoplastic, 151, 156, 160, 187, 195 Antioxidant, 94, 151, 184 Antiviral, 19, 147, 151, 162, 175, 193 Anxiety, 21, 40, 148, 151, 185 Aorta, 103, 151, 201 Aplasia, 151, 163 Apoptosis, 25, 41, 151 Applicability, 24, 151 Aqueous, 151, 161, 172 Arginine, 95, 99, 150, 152, 171, 183, 200 Arrhythmia, 39, 152 Arterial, 29, 43, 152, 172, 190, 198 Arteries, 151, 152, 154, 160, 180, 190 Arterioles, 152, 154, 156, 200 Arteriosus, 152, 190

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Artery, 29, 31, 91, 152, 160, 181, 185, 190, 192 Artificial Eye, 152, 189 Artificial Limbs, 152 Artificial Organs, 27, 72, 152 Aspergillosis, 5, 46, 152, 176 Assay, 5, 20, 30, 33, 82, 152, 173 Atmospheric Pressure, 152, 172 Atrial, 39, 66, 152 Atrial Fibrillation, 39, 152 Atrial Flutter, 39, 152 Atrium, 152, 201 Atrophy, 38, 152 Autoantibodies, 152 Autoantigens, 18, 152 Autoimmune disease, 152, 186 Autoimmunity, 19, 84, 152 Autologous, 30, 42, 100, 152, 170 Autologous bone marrow transplantation, 152, 170 Autopsy, 61, 153 Axonal, 84, 153 B Bacteria, 150, 151, 153, 162, 166, 169, 180, 194, 195, 199, 200 Bacterial Physiology, 147, 153 Bacteriophage, 153, 199 Bacterium, 28, 44, 78, 153, 170 Balloon dilation, 66, 153 Basement Membrane, 153, 166 Basophils, 153, 177 Benign, 68, 153, 170, 182, 191 Benign prostatic hyperplasia, 153 Beta-Thromboglobulin, 153, 175 Bilateral, 48, 57, 89, 91, 96, 153 Bile, 153, 168, 171, 177, 196 Bile duct, 153 Biliary, 75, 153 Biliary Tract, 75, 153 Biochemical, 5, 38, 149, 151, 153, 155, 167 Biological Factors, 22, 153 Biological therapy, 154, 169 Biomarkers, 14, 36, 154 Biopsy, 16, 20, 31, 43, 56, 84, 91, 154 Biotechnology, 43, 44, 117, 129, 154 Biotransformation, 154 Bladder, 153, 154, 189, 200 Blastomycosis, 154, 176 Blood Platelets, 154, 187, 198 Blood pressure, 32, 118, 154, 172, 180, 186, 190

Blood vessel, 150, 154, 156, 158, 164, 166, 170, 176, 178, 179, 186, 195, 197, 198, 200 Body Fluids, 154, 155, 163, 200 Body Mass Index, 78, 79, 154 Bone Marrow, 12, 33, 152, 154, 160, 168, 169, 170, 173, 178, 195 Bone Marrow Transplantation, 33, 154 Bone metastases, 155, 158 Bowel, 114, 150, 155, 162, 175, 186 Brachytherapy, 68, 155, 175, 176, 191, 202 Bradykinin, 155, 183 Bronchi, 68, 155, 165, 199 Bronchial, 19, 49, 58, 87, 91, 94, 101, 155, 171 Bronchioles, 149, 155 Bronchitis, 5, 108, 110, 155, 157 Bronchoalveolar Lavage, 6, 14, 17, 28, 52, 54, 58, 59, 62, 70, 82, 155 Bronchoalveolar Lavage Fluid, 6, 14, 28, 58, 70, 82, 155 Bronchodilator, 5, 51, 155 Bronchopulmonary, 46, 109, 155 Bronchoscopy, 49, 56, 75, 85, 155 Bypass, 39, 155, 181 C Calcineurin, 6, 16, 78, 155 Calcium, 155, 156, 158, 172, 182, 184 Calmodulin, 155, 156 Capillary, 27, 155, 156, 201 Carbohydrate, 114, 156, 160, 188 Carbon Dioxide, 156, 168, 193, 201 Carboplatin, 104, 156 Carcinogenic, 156, 174, 196 Carcinoma, 51, 75, 156, 162 Cardiac, 4, 11, 19, 24, 30, 39, 94, 100, 102, 152, 156, 165, 166, 182, 196 Cardiopulmonary, 4, 51, 72, 156 Cardiovascular, 25, 52, 64, 74, 78, 89, 94, 95, 100, 102, 103, 156, 198 Case report, 66, 85, 87, 103, 156, 158 Case series, 156, 158 Catheter, 80, 156 Causal, 41, 156 Cause of Death, 29, 49, 156, 195 Cell Cycle, 12, 156, 165 Cell Death, 12, 25, 151, 156, 165, 168, 182 Cell Differentiation, 156, 196 Cell Division, 153, 156, 157, 165, 169, 180, 187 Cell proliferation, 12, 25, 157, 175 Cell Respiration, 157, 193 Cell Size, 157, 167

205

Cell Survival, 157, 169 Cell Transplantation, 134, 157, 170 Central Nervous System, 147, 155, 157, 170, 184, 185 Chelation, 102, 157 Chelation Therapy, 102, 157 Chemokines, 6, 9, 22, 35, 157 Chemotactic Factors, 157, 159 Chemotherapy, 6, 69, 101, 104, 157, 176 Cholesterol, 153, 157, 177, 196 Cholinergic, 157, 183 Chromatin, 151, 157, 165 Chromosomal, 5, 149, 157, 171 Chromosome, 157, 177 Chronic Obstructive Pulmonary Disease, 5, 106, 157 Cidofovir, 46, 157 Ciprofloxacin, 45, 157 Circadian, 32, 157 Circadian Rhythm, 32, 157 Circulatory system, 148, 158 C-kit receptor, 158, 196 Clinical Medicine, 158, 188 Clinical study, 26, 158 Clinical trial, 4, 16, 20, 28, 33, 42, 129, 158, 160, 163, 181, 190, 191 Clodronate, 37, 158 Cloning, 154, 158 Colitis, 73, 158 Collagen, 14, 17, 26, 84, 149, 153, 158, 166, 187, 189 Colon, 158, 176, 177 Complement, 10, 14, 24, 37, 150, 158, 159, 179 Complement Activation, 24, 37, 150, 159 Complementary and alternative medicine, 99, 106, 159 Complementary medicine, 99, 159 Computational Biology, 129, 159 Computed tomography, 50, 159 Computerized axial tomography, 159 Computerized tomography, 159 Conception, 147, 159, 166, 189 Congenita, 159, 163 Congestive heart failure, 38, 159 Conjugated, 159, 161 Conjunctiva, 159, 174 Connective Tissue, 26, 154, 158, 160, 167, 169, 178, 179, 194, 198 Connective Tissue Cells, 160 Constriction, 160, 176, 200 Constriction, Pathologic, 160, 200

Continuum, 8, 160 Contraindications, ii, 160 Control group, 160, 189, 191 Conus, 160, 190 Coronary, 31, 160, 180 Coronary Thrombosis, 160, 180 Cortex, 160, 184 Corticosteroid, 38, 160, 188 Cortisone, 160, 189 Cryptococcosis, 80, 160 Curative, 160, 198 Cutaneous, 80, 154, 160, 177, 186 Cyclic, 23, 156, 160, 169, 183, 186 Cyclosporine, 4, 16, 20, 32, 41, 54, 57, 59, 74, 85, 110, 116, 118, 160 Cysteine, 147, 157, 161, 197 Cytochrome, 86, 161 Cytokine, 7, 20, 34, 161, 175, 185, 195 Cytomegalovirus, 44, 46, 47, 48, 51, 57, 58, 60, 61, 68, 69, 73, 82, 83, 88, 89, 104, 161, 168 Cytomegalovirus Infections, 161, 168 Cytoplasm, 151, 153, 161, 164, 165, 193 Cytotoxic, 42, 54, 161, 173, 191 D Data Collection, 11, 14, 34, 161 Decision Making, 14, 89, 161 Deferoxamine, 102, 161 Degenerative, 160, 161, 170 Deletion, 9, 151, 161 Delivery of Health Care, 161, 170 Denaturation, 161, 188 Dendrites, 161, 182 Dendritic, 13, 17, 161 Dendritic cell, 13, 17, 161 Density, 100, 154, 162, 167, 177, 183 Dermal, 162, 163 DES, 150, 162 Desensitization, 162, 173 Deuterium, 162, 172 Dextran Sulfate, 109, 162 Dextrans, 109, 162 Diabetes Mellitus, 162, 170, 185 Diagnostic procedure, 107, 117, 162 Diastolic, 162, 172 Diencephalon, 162, 185 Dietetics, 114, 162 Digestion, 153, 155, 162, 175, 177, 196 Digestive system, 162, 181 Digestive tract, 162, 195 Dihydrotestosterone, 162, 192 Dilation, 155, 162

206

Lung Transplant

Direct, iii, 17, 18, 20, 22, 39, 44, 57, 158, 162, 192 Discrete, 162, 198 Disposition, 46, 162 Dissociation, 148, 162 Distal, 153, 163 Domesticated, 163, 169 Double-blind, 16, 20, 163 Double-blinded, 16, 163 Drug Interactions, 20, 122, 163 Drug Tolerance, 163, 198 Duct, 163, 166, 178, 193, 196 Duodenum, 153, 163, 168, 196 Dyspnea, 32, 163, 190 E Echocardiography, 63, 66, 163 Ectoderm, 163 Ectodermal Dysplasia, 48, 163 Effector, 18, 20, 22, 147, 158, 163, 165, 186 Efficacy, 28, 33, 40, 53, 87, 163 Ehrlichiosis, 85, 163 Elastic, 163, 197 Elastin, 158, 163 Electrolyte, 114, 160, 163, 180, 188 Electrons, 151, 164, 176, 179, 184, 191 Elementary Particles, 164, 179, 182, 190 Embolism, 61, 164, 190 Embryo, 147, 156, 163, 164, 174, 189, 196 Embryo Transfer, 164, 189 Embryogenesis, 164, 196 Emphysema, 14, 29, 38, 50, 81, 108, 149, 157, 164 Empirical, 34, 164 Empyema, 47, 76, 164 Encapsulated, 164, 177 Endocrine Glands, 164 Endogenous, 108, 152, 164, 189 Endometrium, 164, 172 Endothelial cell, 7, 18, 22, 23, 24, 37, 164, 175, 198 Endothelium, 164, 183 Endothelium-derived, 164, 183 Endotoxins, 159, 164 Environmental Health, 128, 130, 164 Enzymatic, 149, 156, 159, 164, 166, 171, 188, 193 Enzyme Induction, 165, 192 Enzyme Repression, 165, 192 Enzyme-Linked Immunosorbent Assay, 59, 165 Eosinophilia, 66, 165 Eosinophils, 165, 177

Epidemiological, 36, 43, 165 Epidermis, 163, 165, 176 Epigastric, 165, 185 Epinephrine, 165, 182, 200 Epithelial, 12, 30, 47, 58, 87, 109, 165, 171 Epithelial Cells, 30, 58, 109, 165, 171 Epithelium, 12, 153, 164, 165 Epitope, 24, 42, 165 Erythrocytes, 149, 154, 165, 192 Esophagus, 162, 165, 186, 192, 196, 198 Etoposide, 104, 165 Excitation, 152, 165, 167, 182 Exhaustion, 150, 166 Exocrine, 166, 185 Exogenous, 108, 154, 164, 166, 189 Expiration, 166, 192, 201 Extensor, 38, 166 External-beam radiation, 166, 176, 191, 202 Extracellular, 8, 25, 26, 160, 166 Extracellular Matrix, 8, 26, 160, 166 Extracellular Space, 166 Extracorporeal, 29, 60, 72, 166, 186 Extracorporeal Membrane Oxygenation, 72, 166 Extraction, 38, 166 Exudate, 155, 166 Eye Infections, 148, 166 F Family Planning, 129, 166 Fat, 61, 114, 154, 160, 166, 177, 195, 197 Fatigue, 166, 170 Feasibility Studies, 8, 166 Fertilization in Vitro, 166, 189 Fetus, 147, 166, 173, 196, 200 Fibrinolytic, 37, 166 Fibroblasts, 14, 22, 26, 41, 160, 166, 175, 181 Fibronectin, 26, 166 Fistula, 49, 167, 168 Flatus, 167, 168 Flexor, 166, 167 Flow Cytometry, 16, 55, 167 Fluorescence, 167 Fluorescent Dyes, 167 Fold, 26, 29, 167, 183 Forced Expiratory Volume, 32, 167 Forearm, 154, 167 Free Radicals, 151, 162, 167, 182 Fungemia, 84, 167 Fungi, 151, 152, 166, 167, 168, 180, 181, 200, 201, 202

207

Fungus, 160, 167, 181 G Gallbladder, 147, 153, 162, 168 Ganciclovir, 46, 53, 54, 58, 61, 68, 95, 99, 104, 168 Gas, 27, 29, 43, 156, 167, 168, 172, 183, 193, 201 Gas exchange, 27, 29, 168, 193, 201 Gastric, 65, 85, 168, 171 Gastroduodenal, 65, 168 Gastrointestinal, 64, 73, 155, 157, 165, 168, 197, 200 Gene, 7, 13, 15, 20, 42, 64, 65, 86, 104, 108, 116, 148, 149, 154, 165, 168, 175, 183 Gene Expression, 13, 15, 168 Gene Therapy, 8, 65, 148, 168 Genetic Code, 168, 183 Genetic testing, 168, 188 Genetics, 21, 168, 173 Genital, 157, 168 Genotype, 168, 186 Giant Cells, 168, 194 Gland, 101, 148, 160, 168, 178, 185, 187, 189, 194, 196, 198 Glomerular, 66, 169, 192 Glucocorticoid, 169, 188, 189 Glucose, 80, 109, 162, 169, 170, 174, 175, 193 Glycoprotein, 116, 149, 166, 168, 169, 181, 198, 200 Gonadal, 169, 196 Governing Board, 169, 188 Graft Rejection, 4, 17, 62, 110, 169, 174, 180 Graft Survival, 31, 169 Grafting, 41, 169, 174 Graft-versus-host disease, 66, 169, 181 Gram-negative, 28, 169 Gram-Negative Bacteria, 28, 169 Granulation Tissue, 155, 169 Granule, 169, 193 Growth factors, 25, 169 Guanylate Cyclase, 169, 183 Guinea Pigs, 103, 169 H Haptens, 148, 169 Hay Fever, 149, 169 Headache, 163, 170, 174 Health Care Costs, 21, 170 Health Education, 21, 170 Health Expenditures, 170 Heart failure, 4, 30, 170, 190 Heart-Lung Transplantation, 60, 103

Hematopoietic Stem Cell Transplantation, 113, 170 Heme, 67, 108, 161, 170, 184 Hemodynamics, 67, 116, 170 Hemoglobin, 165, 170 Hemoglobinopathies, 168, 170 Hemolytic, 86, 170 Hemorrhage, 91, 170, 182, 197 Hepatitis, 68, 89, 170 Hepatocytes, 170, 171 Hereditary, 149, 163, 171 Heredity, 168, 171 Heterogeneity, 148, 171 Histamine, 150, 171 Histamine Release, 150, 171 Histocompatibility, 55, 60, 171, 180 Histocompatibility Antigens, 55, 171, 180 Histology, 15, 16, 17, 20, 171 Histones, 155, 157, 171 Homeostasis, 108, 171 Homogeneous, 160, 171 Homologous, 17, 103, 168, 171, 197 Hormonal, 152, 160, 171 Hormone, 149, 158, 160, 162, 165, 171, 175, 189, 198 Horseradish Peroxidase, 165, 171 Humoral, 10, 17, 20, 44, 60, 169, 171, 199 Humour, 171 Hybrid, 82, 172 Hydrogen, 108, 147, 156, 161, 162, 172, 177, 180, 182, 184, 190 Hydrogen Peroxide, 108, 172, 177 Hydrolysis, 154, 172, 188, 190, 200 Hydrophobic, 102, 172, 177 Hydroxylysine, 158, 172 Hydroxyproline, 149, 158, 172 Hyperbaric, 103, 105, 172 Hyperbaric oxygen, 103, 105, 172 Hypercalcemia, 158, 172 Hyperoxia, 108, 172 Hyperplasia, 68, 172 Hypersensitivity, 16, 162, 172 Hypertension, 29, 106, 108, 170, 172, 182 Hypertrophy, 153, 172 Hypoplasia, 163, 172 Hypothermia, 102, 103, 172 Hypoxemia, 38, 75, 172 Hypoxia, 7, 172 I Idiopathic, 50, 63, 108, 110, 172, 194 Imbedding, 27, 172 Immune function, 16, 20, 173

208

Lung Transplant

Immune Sera, 173 Immune system, 10, 151, 152, 154, 173, 174, 178, 201 Immune Tolerance, 10, 173 Immunization, 17, 20, 148, 173, 174 Immunoassay, 5, 165, 173 Immunocompromised, 85, 173 Immunodeficiency, 48, 173 Immunogenetics, 21, 173 Immunogenic, 26, 173 Immunoglobulin, 150, 173, 181 Immunologic, 10, 11, 148, 157, 173, 185, 191 Immunology, 7, 9, 12, 17, 21, 148, 167, 171, 173 Immunophilin, 155, 173 Immunosuppressant, 173, 195 Immunosuppression, 4, 11, 20, 31, 39, 40, 42, 78, 85, 110, 114, 116, 173, 178, 184 Immunosuppressive Agents, 10, 31, 110, 173 Immunosuppressive therapy, 13, 20, 33, 38, 173, 174 Immunotherapy, 42, 148, 154, 162, 174 Impairment, 38, 148, 166, 174 Implant radiation, 174, 175, 176, 191, 202 Implantation, 159, 172, 174 In situ, 14, 111, 174 In vitro, 6, 11, 19, 26, 30, 42, 94, 103, 108, 109, 164, 168, 174, 187, 194, 198 In vivo, 6, 10, 22, 25, 26, 30, 42, 108, 109, 168, 174, 178, 198 Incision, 174, 176 Induction, 6, 7, 16, 18, 25, 108, 150, 174 Infarction, 153, 160, 174, 180, 192 Influenza, 71, 72, 174 Infusion, 12, 87, 174, 182 Ingestion, 100, 174, 187 Inhalation, 33, 46, 148, 155, 174, 187 Initiation, 18, 24, 37, 41, 174 Innervation, 94, 100, 174 Inositol, 28, 174 Insight, 5, 9, 28, 30, 175 Instillation, 17, 175 Insulin, 26, 175, 185 Insulin-dependent diabetes mellitus, 175 Insulin-like, 26, 175 Interferon, 59, 175 Interferon-alpha, 175 Interleukin-1, 72, 85, 175 Interleukin-10, 85, 175 Interleukin-2, 175

Interleukin-8, 35, 58, 175 Interleukins, 173, 175 Internal radiation, 175, 176, 191, 202 Interstitial, 108, 155, 166, 175, 176, 192, 202 Intestine, 155, 175, 176 Intoxication, 176, 202 Intracellular, 20, 28, 174, 176, 183, 188 Intramuscular, 38, 176 Intravascular, 24, 37, 176 Intravenous, 37, 110, 167, 174, 176 Intrinsic, 38, 148, 153, 176 Invasive, 5, 13, 28, 33, 43, 44, 72, 89, 176, 178 Ions, 156, 162, 163, 172, 176 Irradiation, 108, 176, 180, 202 Ischemia, 6, 9, 23, 33, 36, 37, 94, 95, 152, 176, 181, 192 Isolated lung perfusion, 23, 176 Itraconazole, 54, 57, 59, 176 K Kb, 128, 176 Keratinocytes, 175, 176 Kidney Disease, 66, 108, 118, 128, 176 Kidney Transplantation, 18, 24, 114, 118, 176 Kinetic, 176 L Labile, 158, 176 Large Intestine, 162, 175, 176, 192, 195 Larynx, 108, 177, 199 Latent, 177, 188 Lavage, 17, 28, 50, 177 Leishmaniasis, 90, 177, 185 Lesion, 12, 154, 177, 194, 195 Lethal, 29, 33, 34, 177 Leukemia, 168, 177 Leukocytes, 22, 23, 30, 35, 104, 153, 154, 157, 165, 175, 177, 181, 200 Leukoencephalopathy, 81, 90, 177 Life Expectancy, 34, 40, 177 Ligaments, 160, 177 Ligands, 22, 177 Linkage, 5, 177 Lipid, 33, 84, 175, 177, 184 Lipid Peroxidation, 177, 184 Lipopolysaccharide, 108, 169, 177 Lipoprotein, 169, 177 Liposomal, 37, 177 Liver, 3, 18, 21, 24, 108, 111, 114, 118, 134, 147, 149, 153, 161, 162, 168, 170, 171, 177, 189, 194 Liver Transplantation, 3, 114, 134, 177

209

Living Donors, 62, 177 Localized, 164, 174, 177, 184, 187, 194 Longitudinal Studies, 14, 177 Longitudinal study, 45, 82, 178 Lumbar, 100, 178 Lung volume, 5, 14, 51, 76, 178 Lymph, 158, 164, 171, 178, 194 Lymph node, 178, 194 Lymphatic, 164, 174, 178, 179, 195, 196, 198 Lymphatic system, 178, 195, 196, 198 Lymphocyte, 41, 50, 62, 151, 173, 178, 179, 181 Lymphocyte Depletion, 173, 178 Lymphoid, 13, 150, 169, 178 Lymphokine, 18, 41, 100, 178 Lymphoma, 99, 178, 186 Lymphoproliferative, 42, 47, 52, 59, 80, 82, 100, 101, 104, 178 Lymphoproliferative Disorders, 100, 178 M Macrophage, 24, 34, 48, 50, 70, 175, 178 Magnetic Resonance Imaging, 38, 76, 178, 179 Magnetic Resonance Spectroscopy, 38, 178 Major Histocompatibility Complex, 17, 171, 179, 180 Malignant, 151, 179, 182, 191, 194 Malnutrition, 149, 152, 179 Mammary, 91, 179 Manifest, 7, 153, 179 Mechanical ventilation, 27, 36, 56, 179 Mediate, 10, 17, 22, 28, 179 Mediator, 6, 175, 179, 187 Medical Staff, 163, 179 MEDLINE, 129, 179 Melanin, 179, 186, 200 Membrane, 10, 25, 149, 159, 166, 169, 177, 179, 181, 182, 186, 199 Meningitis, 176, 179 Mental, iv, 4, 128, 130, 162, 163, 166, 179, 190, 192, 194, 200 Mentors, 15, 179 Mercury, 167, 179 Mesenchymal, 41, 179 Methoxsalen, 179, 186 MI, 29, 53, 55, 68, 83, 105, 146, 180 Mice Minute Virus, 180, 185 Microbe, 180, 199 Microbiology, 47, 57, 61, 72, 78, 147, 180 Microorganism, 180, 185, 201

Migration, 35, 180 Mineralocorticoids, 148, 160, 180 Minor Histocompatibility Antigens, 10, 171, 180 Minor Histocompatibility Loci, 180 Mitochondrial Swelling, 180, 182 Mitosis, 151, 180 Mitotic, 165, 180 Modification, 28, 149, 180, 191 Molecule, 18, 36, 108, 151, 159, 162, 163, 164, 165, 166, 170, 172, 180, 184, 187, 191, 200 Monitor, 13, 16, 19, 67, 180, 183 Monoclonal, 10, 24, 176, 181, 191, 202 Monoclonal antibodies, 10, 24, 181 Monocular, 9, 181 Monocyte, 8, 181 Monocyte Chemoattractant Protein-1, 8, 181 Mononuclear, 8, 15, 19, 181, 200 Morphology, 8, 19, 181 Mucociliary, 181, 195 Mucocutaneous, 177, 181 Mucolytic, 147, 155, 181 Mucositis, 6, 181 Multicenter Studies, 6, 181 Multicenter study, 181 Muscle Fibers, 181, 182 Myalgia, 174, 181 Mycophenolate mofetil, 60, 96, 110, 181 Mycosis, 181 Mycotic, 103, 181 Myocardial Reperfusion, 181, 182, 192 Myocardial Reperfusion Injury, 182, 192 Myocardium, 180, 182 Myopathy, 38, 182 Myosin, 19, 155, 182 N Nasal Mucosa, 174, 182 Necrosis, 25, 151, 174, 180, 182, 192, 193, 194 Neoplasm, 182, 194 Neoplastic, 178, 182 Nephrologist, 118, 182 Nephropathy, 176, 182 Nerve, 150, 153, 161, 174, 179, 182, 184, 185, 194, 196, 199 Nervous System, 157, 179, 182, 197 Networks, 6, 182 Neural, 171, 182 Neurons, 161, 182, 183, 197

210

Lung Transplant

Neurotransmitter, 147, 149, 155, 171, 182, 197 Neutrons, 149, 176, 182, 191 Neutropenia, 167, 183 Neutrophil, 35, 149, 183 Nicotine, 104, 183 Nitric Oxide, 33, 67, 90, 96, 183 Nonverbal Communication, 183, 190 Nuclear, 7, 29, 70, 164, 182, 183 Nuclei, 149, 164, 168, 171, 178, 179, 180, 182, 183, 184, 190 Nucleic acid, 57, 168, 183, 193 Nucleolus, 183, 193 Nucleus, 151, 153, 157, 160, 161, 162, 164, 165, 181, 182, 183, 190, 196 Nutrition Assessment, 114, 183 Nutritional Status, 32, 183 O Omentum, 91, 183 Oncogene, 35, 183, 196 Opacity, 162, 183 Operon, 183, 192 Opportunistic Infections, 110, 184 Optic cup, 184, 185 Optic Nerve, 184, 185 Organ Culture, 184, 198 Organ Transplantation, 11, 22, 46, 56, 57, 77, 100, 104, 111, 114, 134, 184 Osteomyelitis, 47, 184 Osteoporosis, 79, 83, 184 Ovalbumin, 41, 184 Overdosage, 84, 184 Ovum, 172, 184, 189 Oxidation, 28, 147, 151, 154, 161, 177, 184 Oxidative Stress, 60, 94, 108, 184 Oxygen Consumption, 184, 193 Oxygenase, 67, 108, 184 Oxygenation, 172, 184 Oxygenator, 166, 184 P Palliative, 34, 184, 198 Pamidronate, 100, 184 Pancreas, 18, 21, 24, 111, 114, 134, 147, 154, 162, 175, 185, 200 Pancreas Transplant, 111, 114, 134, 185 Pancreas Transplantation, 114, 134, 185 Panic, 40, 185 Parotid, 185, 194 Particle, 185, 199 Parvovirus, 46, 180, 185 Pastoral Care, 102, 185 Pathogen, 16, 28, 109, 185

Pathogenesis, 5, 7, 9, 10, 12, 14, 15, 17, 18, 19, 25, 27, 84, 185 Pathologic, 30, 151, 154, 160, 172, 185 Pathologic Processes, 151, 185 Pathophysiology, 12, 21, 30, 185 Pedicle, 91, 185 Pelvis, 178, 185, 200 Penicillin, 150, 185 Pentamidine, 88, 185 Pentoxifylline, 94, 95, 185 Peptide, 25, 41, 42, 149, 185, 188, 189, 190 Perfusion, 23, 28, 38, 43, 62, 172, 185 Perioperative, 57, 186 Peripheral blood, 4, 11, 15, 19, 30, 35, 83, 170, 175, 186 Peripheral Vascular Disease, 108, 186 Peritoneum, 183, 186 Phagocytosis, 28, 186 Pharmacokinetic, 95, 186 Pharmacologic, 20, 150, 186, 199 Pharynx, 174, 186 Phenotype, 8, 14, 27, 52, 62, 186 Phenylalanine, 186, 200 Phosphodiesterase, 185, 186 Phospholipids, 166, 175, 177, 186 Phosphorus, 155, 186 Phosphorylation, 42, 46, 186 Photopheresis, 51, 60, 186 Physical Examination, 114, 186 Physical Therapy, 135, 187 Physiologic, 14, 27, 32, 148, 187, 191 Physiology, 14, 28, 84, 104, 187 Pilot study, 55, 187 Pituitary Gland, 160, 187 Plants, 149, 156, 169, 179, 181, 187, 193, 199, 200 Plasma, 20, 36, 67, 148, 149, 150, 153, 162, 166, 169, 170, 180, 187, 201 Plasma cells, 150, 169, 187 Plasma Volume, 162, 180, 187 Platelet Aggregation, 150, 183, 185, 187 Platelet Factor 4, 175, 187 Platelets, 153, 183, 187, 198 Pneumonia, 49, 72, 108, 109, 155, 160, 185, 187 Pneumonitis, 50, 82, 83, 187 Podophyllotoxin, 165, 187 Poisoning, 157, 176, 179, 187 Polymerase, 86, 187, 192 Polymerase Chain Reaction, 86, 187 Polymers, 162, 188, 190, 197 Polymorphic, 5, 10, 188

211

Polymorphism, 20, 30, 45, 86, 188 Polypeptide, 149, 158, 188, 202 Polysaccharide, 151, 188, 190 Posterior, 150, 152, 185, 188 Postmenopausal, 184, 188 Postoperative, 36, 39, 45, 52, 64, 87, 167, 188 Potassium, 62, 74, 95, 180, 188 Potentiates, 175, 188 Practicability, 166, 188 Practice Guidelines, 130, 188 Preclinical, 26, 30, 188 Precursor, 54, 163, 164, 186, 188, 200 Predisposition, 5, 188 Prednisolone, 188, 189 Prednisone, 31, 189 Pregnancy Outcome, 85, 189 Preoperative, 36, 189 Prevalence, 109, 189 Primary endpoint, 16, 189 Progesterone, 189, 196 Progression, 8, 18, 22, 68, 150, 189, 201 Progressive, 12, 35, 81, 90, 109, 110, 118, 156, 163, 182, 189, 190, 192 Proline, 158, 172, 189 Prophylaxis, 33, 47, 53, 54, 57, 70, 77, 87, 88, 189 Prospective Studies, 33, 189 Prospective study, 11, 63, 178, 189 Prostate, 153, 154, 189, 200 Prostheses and Implants, 152, 189 Protease, 5, 149, 189 Protein Binding, 42, 189 Protein C, 12, 37, 148, 149, 153, 177, 190 Protein S, 154, 168, 190, 193 Proteoglycans, 22, 153, 190 Proteolytic, 25, 149, 158, 190 Protocol, 6, 36, 42, 43, 190 Protons, 149, 172, 179, 190, 191 Protozoa, 177, 180, 190, 200 Psychiatry, 40, 190, 201 Psychoactive, 190, 202 Psychotherapy, 41, 190 Public Policy, 129, 190 Publishing, 44, 190 Pulmonary Artery, 7, 29, 154, 190, 201 Pulmonary Embolism, 70, 108, 190 Pulmonary Fibrosis, 4, 7, 22, 50, 63, 110, 190 Pulmonary hypertension, 4, 29, 66, 83, 88, 96, 108, 116, 190 Pulse, 180, 190

Pyogenic, 184, 190 Q Quality of Life, 14, 20, 32, 34, 35, 39, 40, 47, 51, 52, 55, 59, 67, 81, 83, 96, 105, 135, 191 R Race, 180, 191 Radiation, 101, 164, 166, 167, 172, 173, 175, 176, 191, 202 Radiation therapy, 166, 172, 175, 176, 191, 202 Radioactive, 43, 172, 174, 175, 176, 181, 183, 191, 202 Radiolabeled, 176, 191, 202 Radiotherapy, 155, 176, 191, 202 Random Allocation, 191 Randomization, 21, 28, 191 Randomized, 3, 16, 20, 21, 30, 31, 32, 33, 40, 69, 91, 163, 191 Randomized clinical trial, 20, 91, 191 Reactivation, 48, 191 Reagent, 162, 191 Receptor, 8, 9, 21, 22, 25, 34, 72, 111, 147, 151, 158, 191 Recombinant, 44, 111, 191, 200 Recombination, 168, 192 Rectum, 158, 162, 167, 168, 176, 189, 192 Recurrence, 157, 192 Red blood cells, 165, 170, 184, 192, 194 Reductase, 41, 192 Reentry, 39, 192 Refer, 1, 158, 167, 182, 192, 199 Reflux, 64, 73, 192 Refractory, 104, 110, 192 Regimen, 21, 31, 33, 40, 163, 192 Rehabilitative, 104, 192 Reliability, 59, 192 Renal failure, 192 Reperfusion, 6, 9, 23, 33, 36, 37, 94, 95, 116, 181, 182, 192 Reperfusion Injury, 6, 9, 23, 34, 36, 94, 95, 116, 192 Repressor, 42, 183, 192 Repressor Proteins, 42, 192 Reproduction Techniques, 189, 192 Research Support, 36, 192 Resection, 74, 89, 192 Respiration, 23, 46, 67, 91, 156, 180, 192 Respirator, 179, 193 Respiratory distress syndrome, 29, 46, 108, 193 Respiratory failure, 27, 110, 166, 193

212

Lung Transplant

Respiratory Physiology, 45, 46, 70, 75, 80, 87, 193, 201 Retinal, 181, 184, 193 Retrospective, 11, 31, 36, 43, 193 Retroviral vector, 168, 193 Rhabdomyolysis, 54, 193 Rheology, 185, 193 Ribavirin, 52, 193 Ribose, 147, 193 Ribosome, 42, 193, 199 Risk factor, 5, 15, 31, 36, 43, 47, 59, 63, 65, 77, 84, 110, 189, 193 Rod, 153, 193 Rubber, 27, 147, 193 S Saline, 155, 193 Salivary, 161, 162, 193 Salivary glands, 161, 162, 193 Saponins, 193, 196 Sarcoidosis, 63, 79, 115, 194 Sarcoma, 73, 194 Schizoid, 194, 202 Schizophrenia, 194, 202 Schizotypal Personality Disorder, 194, 202 Scleroderma, 27, 106, 194 Sclerosis, 26, 194 Screening, 5, 56, 116, 158, 194 Secretion, 94, 158, 160, 171, 175, 180, 194 Secretory, 54, 87, 194, 197 Segmental, 74, 194 Segmentation, 194 Semisynthetic, 165, 194 Senile, 184, 194 Sepsis, 108, 167, 194 Septic, 48, 108, 194 Sequela, 19, 194 Sequencing, 188, 194 Sequester, 42, 157, 194 Serologic, 173, 194 Serology, 59, 82, 194 Serum, 20, 54, 148, 150, 158, 159, 173, 178, 180, 194, 200 Shedding, 25, 195 Shock, 108, 195, 200 Side effect, 16, 20, 121, 123, 148, 154, 195, 199 Sil, 30, 195 Sinusitis, 44, 72, 195 Sirolimus, 28, 58, 116, 195 Skeletal, 38, 150, 193, 195 Skeleton, 147, 195 Skin graft, 41, 195, 196

Skull, 195, 198 Small intestine, 3, 163, 171, 175, 195, 200 Smoke Inhalation Injury, 166, 195 Smooth muscle, 150, 155, 160, 171, 195, 197 Sneezing, 195 Social Environment, 191, 195 Soft tissue, 154, 195 Solid tumor, 150, 195 Somatic, 164, 171, 180, 195 Spasmogenic, 150, 195 Specialist, 136, 162, 195 Specificity, 16, 20, 24, 42, 148, 196 Sphincter, 177, 196 Spirometry, 5, 43, 67, 196 Spleen, 108, 161, 178, 194, 196 Spontaneous Abortion, 189, 196 Sputum, 71, 85, 196 Staging, 80, 196 Standard therapy, 186, 196 Stem Cell Factor, 25, 158, 196 Stem Cells, 169, 170, 196 Stenosis, 65, 68, 196, 197 Stents, 65, 87, 196 Steroid, 31, 160, 193, 196 Stillbirth, 189, 196 Stimulus, 165, 174, 175, 196, 198 Stomach, 147, 162, 165, 168, 171, 177, 183, 186, 192, 195, 196 Strand, 187, 196 Stress, 10, 21, 36, 100, 108, 184, 188, 193, 196 Stricture, 196, 197 Stroke, 39, 128, 197 Styrene, 193, 197 Subacute, 174, 195, 197 Subclinical, 174, 197 Subcutaneous, 85, 103, 197 Subspecies, 196, 197 Substance P, 194, 197 Substrate, 108, 165, 192, 197 Sulfur, 162, 197 Support group, 135, 197 Suppression, 160, 197 Suppressive, 16, 197 Surfactant, 28, 90, 197 Symptomatic, 47, 197 Symptomatology, 40, 197 Synaptic, 182, 183, 197 Synaptic Transmission, 183, 197 Systolic, 172, 198

213

T Tacrolimus, 3, 6, 28, 57, 76, 85, 86, 110, 198 Temporal, 15, 198 Tendon, 45, 198 Testosterone, 192, 198 Therapeutics, 122, 198 Thermal, 162, 182, 188, 198 Thoracic Surgery, 45, 48, 49, 52, 57, 58, 62, 65, 68, 71, 74, 75, 77, 94, 96, 103, 105, 198 Thorax, 46, 49, 71, 77, 100, 178, 198 Threshold, 38, 172, 198 Thrombin, 187, 190, 198 Thrombocytopenia, 76, 198 Thrombomodulin, 190, 198 Thrombosis, 153, 190, 197, 198 Thrombus, 160, 174, 181, 187, 198, 201 Thymus, 173, 178, 198 Thyroid, 198, 200 Tissue Culture, 12, 198 Tolerance, 12, 16, 26, 38, 41, 57, 108, 147, 198 Tomography, 53, 80, 179, 199 Tone, 94, 199 Tonus, 199 Tooth Preparation, 147, 199 Topical, 172, 199 Toxic, iv, 33, 110, 183, 185, 187, 195, 197, 199 Toxicity, 3, 33, 110, 163, 179, 199 Toxicokinetics, 199 Toxicology, 29, 130, 199 Toxin, 198, 199 Trachea, 155, 177, 186, 198, 199 Transduction, 35, 155, 175, 199 Transfection, 154, 168, 199 Transfer Factor, 173, 199 Translation, 8, 41, 149, 199 Translational, 15, 36, 42, 199 Translocation, 6, 199 Transmitter, 147, 179, 199 Transplantation Tolerance, 18, 54, 199 Trauma, 29, 170, 182, 200, 202 Trees, 193, 200 Trypanosomiasis, 185, 200 Trypsin, 149, 200, 202 Tryptophan, 158, 200 Tuberculosis, 76, 200 Tumor marker, 154, 200 Tumor Necrosis Factor, 85, 94, 200 Tyrosine, 25, 200

U Uremia, 192, 200 Urethra, 153, 189, 200 Urinary, 157, 200 Urine, 6, 153, 154, 200 Uterus, 147, 164, 172, 189, 200 V Vaccines, 200, 201 Vascular, 19, 24, 29, 75, 89, 108, 164, 169, 174, 183, 198, 200 Vascular Resistance, 29, 200 Vasoconstriction, 24, 165, 200 Vasodilator, 77, 155, 171, 181, 200 Vector, 8, 199, 200 Vein, 176, 183, 185, 201 Venous, 62, 63, 66, 153, 190, 201 Venous blood, 62, 201 Venous Thrombosis, 63, 153, 201 Ventilation, 28, 34, 43, 57, 201 Ventricle, 29, 190, 198, 201 Ventricular, 30, 96, 182, 201 Venules, 154, 156, 201 Vertebral, 61, 83, 201 Veterinary Medicine, 129, 201 Viral, 19, 47, 72, 82, 83, 86, 101, 110, 147, 168, 174, 199, 201 Viral Load, 82, 83, 101, 201 Viremia, 70, 82, 201 Virulence, 199, 201 Virus, 42, 48, 53, 59, 68, 82, 89, 99, 153, 168, 175, 193, 199, 201 Visceral, 90, 177, 186, 201 Viscosity, 147, 193, 201 Vital Capacity, 167, 201 Vitamin A, 174, 201 Vitro, 7, 12, 42, 201 Vivo, 7, 11, 12, 22, 30, 43, 65, 178, 201 Voriconazole, 87, 201 W White blood cell, 150, 177, 178, 181, 183, 187, 201 Withdrawal, 11, 31, 202 Wound Healing, 25, 108, 202 Wound Infection, 55, 64, 202 X Xenograft, 24, 37, 150, 202 X-ray, 150, 159, 167, 176, 183, 191, 202 X-ray therapy, 176, 202 Y Yeasts, 167, 186, 202 Z Zymogen, 190, 202

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