BRONCHITIS 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 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Bronchitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83802-X 1. Bronchitis-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:
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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 bronchitis. 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 BRONCHITIS .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bronchitis...................................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 62 CHAPTER 2. NUTRITION AND BRONCHITIS .................................................................................... 97 Overview...................................................................................................................................... 97 Finding Nutrition Studies on Bronchitis..................................................................................... 97 Federal Resources on Nutrition ................................................................................................. 102 Additional Web Resources ......................................................................................................... 103 CHAPTER 3. ALTERNATIVE MEDICINE AND BRONCHITIS ............................................................ 105 Overview.................................................................................................................................... 105 National Center for Complementary and Alternative Medicine................................................ 105 Additional Web Resources ......................................................................................................... 111 General References ..................................................................................................................... 121 CHAPTER 4. DISSERTATIONS ON BRONCHITIS .............................................................................. 123 Overview.................................................................................................................................... 123 Dissertations on Bronchitis........................................................................................................ 123 Keeping Current ........................................................................................................................ 124 CHAPTER 5. CLINICAL TRIALS AND BRONCHITIS ......................................................................... 125 Overview.................................................................................................................................... 125 Recent Trials on Bronchitis........................................................................................................ 125 Keeping Current on Clinical Trials ........................................................................................... 126 CHAPTER 6. PATENTS ON BRONCHITIS ......................................................................................... 129 Overview.................................................................................................................................... 129 Patents on Bronchitis................................................................................................................. 129 Patent Applications on Bronchitis ............................................................................................. 146 Keeping Current ........................................................................................................................ 167 CHAPTER 7. BOOKS ON BRONCHITIS ............................................................................................ 169 Overview.................................................................................................................................... 169 Book Summaries: Federal Agencies............................................................................................ 169 Book Summaries: Online Booksellers......................................................................................... 170 The National Library of Medicine Book Index ........................................................................... 173 Chapters on Bronchitis............................................................................................................... 175 CHAPTER 8. MULTIMEDIA ON BRONCHITIS .................................................................................. 179 Overview.................................................................................................................................... 179 Video Recordings ....................................................................................................................... 179 Bibliography: Multimedia on Bronchitis ................................................................................... 180 CHAPTER 9. PERIODICALS AND NEWS ON BRONCHITIS ............................................................... 183 Overview.................................................................................................................................... 183 News Services and Press Releases.............................................................................................. 183 Newsletter Articles .................................................................................................................... 185 Academic Periodicals covering Bronchitis ................................................................................. 186 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 187 Overview.................................................................................................................................... 187 U.S. Pharmacopeia..................................................................................................................... 187 Commercial Databases ............................................................................................................... 189 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 193 Overview.................................................................................................................................... 193
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NIH Guidelines.......................................................................................................................... 193 NIH Databases........................................................................................................................... 195 Other Commercial Databases..................................................................................................... 198 APPENDIX B. PATIENT RESOURCES ............................................................................................... 199 Overview.................................................................................................................................... 199 Patient Guideline Sources.......................................................................................................... 199 Finding Associations.................................................................................................................. 204 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 207 Overview.................................................................................................................................... 207 Preparation................................................................................................................................. 207 Finding a Local Medical Library................................................................................................ 207 Medical Libraries in the U.S. and Canada ................................................................................. 207 ONLINE GLOSSARIES................................................................................................................ 213 Online Dictionary Directories ................................................................................................... 214 BRONCHITIS DICTIONARY..................................................................................................... 215 INDEX .............................................................................................................................................. 301
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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 bronchitis 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 bronchitis, 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 bronchitis, 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 bronchitis. 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 bronchitis, 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 bronchitis. 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 BRONCHITIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bronchitis.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and bronchitis, 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 “bronchitis” (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: •
Potential Associations Between Chronic Respiratory Disease and Periodontal Disease: Analysis of National Health and Nutrition Examination Survey III Source: Journal of Periodontology. 72(1): 50-56. January 2001. Contact: Available from American Academy of Periodontology. 737 North Michigan Avenue, Suite 800, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Associations between poor oral health and chronic lung disease have recently been reported. This article reports on a study that evaluated these potential associations by analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), which documents the general health and nutritional status of randomly selected United States subjects from 1988 to 1994. This cross sectional, retrospective study of the NHANES III database included a study population of 13,792 subjects older
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than 20 years of age, with at least 6 natural teeth. A history of bronchitis or emphysema was recorded from the medical questionnaire, and a dichotomized variable combined those with either chronic bronchitis or emphysema, together considered as chronic obstructive pulmonary disease (COPD). Subject lung function and oral health status were assessed. Analyses adjusted for age, gender, race and ethnicity, education, income, frequency of dental visits, diabetes mellitus, smoking, and alcohol use. The mean age of all subjects was 44.4 years (plus or minus 17.8 years); the mean age of subjects with COPD was 51.2 years and subjects without COPD was 43.9 years. Subjects with a history of COPD had more periodontal attachment loss (a measure of periodontal disease) than subjects without COPD. A trend was noted in that lung function appeared to diminish with increasing periodontal attachment loss. The authors conclude that these findings support recently published reports that suggest an association between periodontal disease and COPD. 4 tables. 46 references. •
Mortality Preventable by Medical Intervention: Ethnic and Regional Differences in Texas Source: Journal of the National Medical Association. 87(11): 820-825. November 1995. Summary: In this article, the authors report on their examination of mortality from 12 causes of death, as tabulated for the State of Texas for residents in the Lower Rio Grande Valley, for residents of border counties, for residents of Dallas, Harris, and Tarrant counties, along with residents of east Texas from 1980 to 1989. The ninth revised edition of the International Classification of Diseases was used to categorize causes of mortality. From 1980 to 1989, an average of 1,543 deaths per year was attributed to these 12 selected causes in Texas. Thirty-two percent of deaths were due to hypertensive heart disease, 30 percent to pneumonia and bronchitis, 11 percent to cervical cancer, and 6 percent to rheumatic fever. Other causes of death included appendicitis, hernia, and cholecystitis. 3 tables. 19 references. (AA-M).
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Managing the Patient with Severe Respiratory Problems Source: CDA Journal. Journal of the California Dental Association. 28(8): 585-586, 588589, 591-593, 595-598. August 2000. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: The dental management of patients with severe respiratory problems continues to be a significant challenge to the dental health care practitioner. Chronic obstructive pulmonary diseases, such as chronic bronchitis and emphysema, are the fourth leading cause of death in the United States. Asthma has increased in prevalence during the past 20 years, and the rate of death from this chronic inflammatory disease of the airways has also risen despite recent advances in medical treatments. This article reviews the pathophysiology and medical treatment modalities for these chronic pulmonary diseases. The author also discusses the recognition and management of dental patients with these diseases, including how to avoid precipitating factors that could initiate an acute episode in the dental setting. The author notes that because dentists operate at the origin of the upper airway, and many dental procedures are deemed stressful, patients with chronic respiratory diseases are at special risk. The author provides detailed suggestions for preventing and managing respiratory distress in the dental setting. The entire dental team should be familiar with the signs, symptoms, and management of an emergent episode associated with asthma or chronic obstructive pulmonary diseases. 2 tables. 41 references.
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Cause of Death in Alzheimer's Disease Source: Annals of Epidemiology. 6(3): 195-200. May 1996. Summary: This article describes a study comparing the causes of death among 917 patients with Alzheimer's disease (AD) in Rochester, Minnesota, whose onset of symptoms occurred during from 1960 to 1984, with a control group of 701 people matched by age and gender. The purpose was to determine the usefulness of death certificate information for studying dementing illnesses. A summary of the diagnostic codes entered on a death certificate may suggest that control subjects had more cardiovascular disease and neoplasms than did AD patients, who more often had a diagnostic code of bronchitis/pneumonia. Using logistic regression, this difference remained statistically significant after adjusting for age and gender. In this community only 11.1 percent of patients known to have AD before death had dementia noted anywhere on their death certificates. 1 figure, 5 tables, 13 references. (AA-M).
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Uncovering Lesser-Known Symptoms of GERD Source: Digestive Health and Nutrition. 4(2):6. March-April 2002. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email:
[email protected]. Summary: This article describes some of the lesser known symptoms of gastroesophageal reflux disease (GERD), which are usually separated into three groups: pulmonary (asthma and chronic bronchitis); ear, nose and throat (cough, hoarseness, changing of the voice); and other, including chest pain. The author emphasizes that any chest pain indicates the need for a complete work up, to eliminate the possibility of heart disease. In addition to heartburn, the most common symptoms of GERD are chronic cough, hoarseness, sore throat, frequent clearing of the throat in the morning, and asthma. Some studies suggest that up to 80 percent of adult onset asthma that is not allergy related may be caused by acid reflux, especially if the episodes are frequent at night. The author also notes that an endoscopy performed on a patient with extraesophageal symptoms will usually come back normal, and more sophisticated testing will need to be done to prove a connection. 1 reference.
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Impact of Febrile Infections on the Long-Term Function of Kidney Allografts Source: Journal of Urology. 166(6): 2048-2052. December 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study that prospectively determined the impact of febrile (with fever) infectious disease on long term renal (kidney) graft function compared with a matched control group. Included in the study were 39 patients who presented with episodes of febrile infection with body temperature greater than 38C (or 100.4 F) on two consecutive occasions, necessitating hospitalization. In addition, 39 controls without febrile infection requiring hospitalization within 2 months were chosen from the complete data pool of all renal transplant recipients followed at the transplant clinic. Renal function was estimated by serum creatinine and calculated creatinine clearance. Of the 39 patients with infection, 15 had urinary tract infection (UTI) and 24 had other, mostly bacterial infection, including pneumonia or severe bronchitis in 12 patients, oral or dental infection in 2 patients, gastroenteritis in 2 patients, shunt sepsis in 1 patients, herpes zoster in 1 patient, cytomegalovirus in 1 patient, and other
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infections in 5 patients. Mean estimated creatinine clearance rates (a measure of kidney function) were similar in the infection and control groups at the beginning of the study. During the infectious episode, mean creatinine clearance significantly decreased in the infection group. After infection resolved, creatinine clearance in this group returned to almost baseline value. However, after 2 years of followup there was a significant difference in mean creatinine clearance in the infection group versus controls. The authors conclude that this is the first data from a prospective controlled study that shows febrile infectious episodes correlate with poor long term renal graft function. 1 figure. 2 tables. 32 references. •
Chronic Cough Source: American Family Physician. 56(5): 1395-1402. October 1, 1997. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article reviews chronic cough, defined as a cough that lasts for more than three weeks, and updates readers on the current thinking regarding treatment options. The author notes that more than 90 percent of cases of chronic cough result from five common causes: smoking, post-nasal drip, asthma, gastroesophageal reflux, and chronic bronchitis. Although in most patients chronic cough has a single cause, in up to one fourth of patients, multiple disorders contribute to the cough. A stepwise evaluation in patients with chronic cough can minimize the invasiveness and expense of the work up. Initial screening of patients with chronic cough should look for smoking, occupational exposure to an airway irritant, cough-inducing medications, airway hyperresponsiveness following upper respiratory infection, chronic bronchitis, or any systemic symptoms that may indicate serious disease. Patients who are not diagnosed after an initial screening are evaluated and empirically treated in a stepwise fashion for postnasal drip, asthma, and reflux. Bronchoscopy is reserved for use in the few patients still without a diagnosis after the previous steps have been completed. 1 figure. 2 tables. 32 references. (AA-M).
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Relation Between Morbidity and Cognitive Performance in a Normal Aging Population Source: Journal of Gerontology: Medical Sciences. 53A(2): M147-M154. 1998. Summary: This journal article describes a study of the association between morbidity and cognitive performance in an aging population of 1,360 community residents who were enrolled in the Maastricht Aging Study, the Netherlands. People with evidence of stroke, chronic neurological pathology, mental retardation, or chronic psychotropic drug use were excluded. Standard neuropsychological tests were used to assess memory, sensorimotor speed, and information processing speed/cognitive flexibility. Data concerning active and total (active plus inactive) health problems were obtained from a computerized patient database, and classified according to the International Classification of Primary Care. Multiple regression analyses adjusted for age, sex, and educational level revealed that both insulin-dependent and noninsulin-dependent diabetes were negatively associated with all cognitive measures. Negative associations also were found between chronic bronchitis and performance speed, and between presbyacusia and memory. The authors conclude that some specific, relatively common diseases of older age, such as diabetes and chronic bronchitis, may contribute to the age-related decline in cognitive ability. 3 tables, 30 references. (AA-M).
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Poison Ivy Update Source: Patient Care. 33(9): 214-216,221-222,225,229-230,233,237. May 15, 1999. Summary: This journal article provides health professionals with updated information on the clinical presentation, treatment, and prevention of poison ivy, poison oak, and poison sumac. The poison in these plants is the chemical urushiol. This chemical is contained in the leaves, stems, roots, flowers, and berries of the plants. The yellowish-toclear urushiol will turn black when exposed to air, so black spots on a plant are a good indication that it is poison ivy or a related plant. A skin eruption can be prevented if a person who is aware of making contact with poison ivy takes quick action, including washing with plain water or washing with water and soap or an oxidizing agent. Clinical presentation consists of a linear group of itchy, red spots at the point of contact with urushiol. Pruritus and erythema are accompanied by edema. Smoke from burning plants that carries urushiol can cause a diffuse dermatitis. If inhaled, urushiol can cause bronchitis or pneumonitis. Without treatment, a mild case of poison ivy will resolve in about 2 weeks. Relief from symptoms may be obtained using cool compresses with astringents such as aluminum acetate solution or soaks with colloidal oatmeal. Calamine lotion may also be helpful. Corticosteroids should be reserved for more serious cases. Injected corticosteroids are warranted in cases in which urushiol has been inhaled or swallowed. There is no scientific evidence to support the use of herbal remedies. Prevention involves being able to recognize the varieties of poison ivy, poison oak, and poison sumac. In addition, a lotion with organoclay as the active ingredient has been shown to provide protection for people who are mildly to moderately sensitive to poison ivy. 8 figures, 1 table, and 4 references.
Federally Funded Research on Bronchitis The U.S. Government supports a variety of research studies relating to bronchitis. 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 bronchitis. 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 bronchitis. The following is typical of the type of information found when searching the CRISP database for bronchitis: •
Project Title: AEROSOL CYCLOSPORINE FOR PREVENTION OF LUNG REJECTION Principal Investigator & Institution: Iacono, Aldo T.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
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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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Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Success with lung transplantation has largely been due to the introduction of cyclosporine which has proved effective in controlling lung allograft refection. Nevertheless, acute and chronic rejection are prevalent in spite of immunosuppressive drug regimens based on oral cyclosporine. In fact, rejection is more common in recipients of lung allografts than those who receive other solid organs. Acute rejection is treated with pulsed methylprednisolone and anti-lymphocyte globulin and consequently recipients are subject to increased risk of infection and drug toxicity. We hypothesize that delivery of cyclosporine to the transplanted lung by aerosol inhalation achieves higher concentrations of cyclosporine in the graft than when it is delivered via the bloodstream and that higher concentrations in the graft will prevent rejection more effectively that systemic immune suppression with the same or reduced toxicity. Clinical trials at the University of Pittsburgh have shown safety and efficacy of aerosolized cyclosporine utilized as rescue in over 40 patients with refractory rejection unresponsive to conventional augmented immune therapy. In this protocol, we propose a double blinded placebo controlled trial evaluating the efficacy of aerosolized cyclosporine given in addition to the standard oral immunosuppressive drug regimen, in preventing acute rejection immediately after lung transplantation. Deposition of aerosol cyclosporine will be measured by radioisotopic techniques to optimize the dose to the allograft and define the relationship between dose deposited and improvement in parameters of rejection. The results of this study will help determine whether regional delivery of aerosol cyclosporine is effective as prevention and treatment of acute rejection in lung transplant recipients and better define the potential toxicities and beneficial effects of delivery of immunosuppressive medication to the lower respiratory tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AIR PARTICLES CAUSE DEATH IN ANIMALS WITH LUNG DISEASE Principal Investigator & Institution: Godleski, John J.; Associate Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001 Summary: This project will define the effects of concentrated air particles in an animal model of chromic bronchitis. It will determine the role of concentration vs composition in producing adverse effects. The project focuses upon discovery of mechanisms of death and morbidity caused by ambient air particles in animals with pre-existing pulmonary inflammation and airway hyperresponsiveness. Specific aims are: 1) To define the extent of mortality resulting from exposure to various levels of concentrated ambient air particles (CAPs) using normal adult rats and rats with chronic bronchitis; and 2) To determine the mechanisms by which inflammation contributes to mortality and morbidity from exposure to CAPs in the rat model of chronic bronchitis, and 3) To characterize the degree of airway obstruction and hypoventilation present in rats with chronic bronchitis that could lead to increased morbidity and mortality with exposure to CAPs. To assess effects of ambient air particles, animals will be exposed using the Harvard Ambient Particulate Concentration (HAPC), a newly developed device that can increase ambient particle concentrations up to thirty times ambient levels without changing the physical or chemical characteristics of the particles. The exposed animal populations will model human populations and adverse effects including increased mortality that have been identified epidemiologically. Concentrating airborne particles for use in exposures will permit the populations studied in the laboratory to be of a size to see the modeled effect and a size unable to test mechanistic hypotheses. Exposures
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will take place in Boston, MA, which has a typical fine particle urban aerosol ranging from 5-15 gu/m3 with transported sulfur-containing acidic particles during the summer and local combustion product particulate in winter. With Core support, extensive physical, chemical, andmicrobiologic analysis of the exposure aerosol will be carried out with correlation between these parameters and biologic responses of the animals. Established physiologic methods will probe airway responses and their mechanisms. Cell and molecular biology methods will test mechanistic hypotheses on the role of proinflammatory mediators in the development of morbidity and mortality. The novel application of of sophisticated techniques in our proposed studies will offer new insights into mechanisms of toxicity of ambient air particles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AIRWAY INFLAMMATION & MEDIATORS IN CHRONIC BRONCHITIS Principal Investigator & Institution: Knowles, Michael R.; Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AIRWAY SECRETION IN RECURRENT AIRWAY OBSTRUCTION Principal Investigator & Institution: Jefcoat, Andrew M.; Large Animal Clinical Sciences; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 10-SEP-2001 Summary: The goal of this project is to quantify airway secretory activity in horses with recurrent airway obstruction (RAO), to investigate mechanisms underlying increased production and accumulation of airway secretions, and to assess the functional significance of this increase. Equine RAO mimics many of the changes observed in human diseases, such as chronic asthma, chronic bronchitis, and organic dust-induced airway disease, in which persistent mucus overproduction is an important component of airway obstruction. Immunochemical, morphometric, functional, and in vitro methods will be utilized to identify temporal alterations in the production, secretion, and intraepithelial storage of mucus/mucus-like material in disease-affected horses versus controls, and to assess the functional significance of any such alterations. In addition, mechanisms of increased secretion will be addressed by evaluating the effect of neutrophil elastase and endotoxin on airway secretory activity. It is my general hypothesis that equine RAO is associated with a persistent increase in mucus production that contributes to airway obstruction even during periods of apparent disease remission, that increased intraepithelial storage accompanies this persistent increase, and that increased concentrations of the inflammatory mediator neutrophil elastase or a hypersensitivity to this mediator contributes to increased secretory activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AIRWAY SMOOTH MUSCLE IN HEALTH AND DISEASE Principal Investigator & Institution: Coburn, Ronald F.; Physiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-APR-1987; Project End 30-APR-2004
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Summary: (Applicant's Abstract): Our long-term goal is to better understand signal transduction systems that control airway smooth muscle tone, both in normal and in diseased airways. We have emphasized investigation of inositol phospholipidphosphate signal transduction. The proposed experiments follow our data and data obtained by others that indicate muscle length controls muscarinic agonist-evoked phosphatidylinositol (PI) turnover. The site of control of PI turnover in the PI cycle and the length or strain sensors that provide signals that control PI turnover are unknown. We will test the postulate that the length-strain sensor that controls PI turnover is a 51 intergrin receptor and study characteristics of this length sensor system. We will test the postulate, supported by our preliminary data, that length effects on PI turnover are effected by controlling phosphatidylinositol 4-kinase-mediated conversion of PI to PI-4phosphate. We will utilize two preparations: intact muscle and isolated low buoyant density microdomains. Studies in intact muscle are directed to determine relationships of muscle length-dependent 51 integrin inward signaling and muscle length-dependent PI turnover. We will determine if length-dependent CARB-evoked paxillin tyrosine phosphorylation, a measurement of integrin signaling, is dependent on activation of Rho A, if it is inhibited by pretreatment of the muscle with c3 exotoxin, and if this treatment prevents muscle length-dependent CARB-evoked PI turnover. Following our finding that the majority of cellular paxillin is present in cytosol, we will investigate if cytoplasmic paxillin is involved in integrin signaling. Isolating low buoyant density microdomains offers another approach to study how PI turnover can be activated by muscarinic and length signals. We plan to determine if PI turnover channels through these small domains and if PI transfer proteins function in activation of P14Kase in these domanins during length-dependent muscarinic activation of the muscle. Proposed experiments should produce data important to our understanding of the mechanaisms of length-dependent signaling which are relevant to improving our understanding of airway smooth muscle function in vivo. Airway smooth function is markedly altered in many different lung diseases, including asthma, bronchitis and emphysema. In particular, all of these diseases cause physiological alterations that influence the length at which smooth muscle cells contract and relax. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AIRWAYS-CNS CENTRAL NERVOUS SYSTEM Principal Investigator & Institution: Haxhiu, Musa A.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 30-JUN-2003 Summary: (Applicant's abstract): This project is based on the assumption that knowledge of the central homeostatic mechanisms that regulate airway functions is of critical importance in understanding the link between the nervous system and pathophysiology of airway disorders such as bronchial asthma and chronic obstructive bronchitis. In the proposed studies, which are a logical continuation of the ongoing work in this laboratory, we will identify brainstem 2nd order neurons within the nucleus tractus solitarius (nTS) which receive excitatory inputs from airway sensory sites, and study the neurotransmitter phenotype and receptor make-up of these neurons. In 0addition, we will define the role of excitatory amino acids and tachykinin 1peptides in transmission of signals from primary sensory cells onto second order (nTS) neurons, and their role in subsequent transmission of signals to airway related vagal preganglionic cells. Our studies will test the hypothesis that tonic cholinergic activity, reflexly induced airway constriction and submucosal gland secretion are mediated primarily via release of endogenous excitatory amino acids and co-release of substance
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p. In the proposed studies we will use 1) molecular biological approaches such as expression of c-Fos protein, encoded by the c-fos gene, to identify neurons in the nTS which are activated by stimulation of bronchopulmonary sensory receptors, 2) receptor immunocytochemistry and confocal microscopy to determine receptor(s) expressed by nTS sensory neurons and airway-related vagal preganglionic cells, 3) microdialysis and in situ voltametry, to measure neurotransmitter release, 4) selective receptor blockade and physiologic techniques to determine the role of receptors studied on reflex bronchoconstriction and reflex increase in submucosal gland secretion. The present proposal will provide information on the functional neurochemical anatomy of central regulation of cholinergic outflow, on neurotransmitter and receptor subtypes mediating airway responses to peripheral afferent inputs, and on interaction between neurochemicals that might set the stage for airway hypersensitivity and hyperreactivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF THE AIRWAY ANTIPROTEINASE DEFENSE SYSTEM Principal Investigator & Institution: Cataltepe, Sule U.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (Adapted from applicant's abstract) Proteinases play a major role in the development of inflammatory lung diseases such as cystic fibrosis, asthma, chronic bronchitis, emphysema and chronic lung disease of prematurity. A better understanding of the regulation of proteinases by inhibitors synthesized by the lung itself could facilitate efforts to develop specific treatments for these diseases. Squamous cell carcinoma antigens (SCCA) 1 and 2 are members of the high molecular weight serine proteinase inhibitor (serpin) family. Although SCCA1 inhibits lysosomal cysteine proteinases, cathepsins (cat)L,S and K, whereas SCCA2 inhibits chymotrypsin-like serine proteinases, catG and mast cell chymase. SCCA1 and SCCA2 show a tissue restricted expression pattern and are co-localized in the tracheal, bronchial and bronchiolar epithelium. In addition, target proteinases of SCCA1, catS and catK, are expressed by the airway epithelial cells. Another source of these potent elastolytic cysteine proteinases in the lung is alveolar macrophages. Based on the in vitro inhibitory profiles and distribution patterns of SCCA1 and SCCA2 in the airways, the investigators hypothesize that these two serpins protect the airways against proteinase mediated injury. The objective of this proposal is to test this hypothesis using in vitro cell culture and in vivo transgenic animal models. The specific aims of the proposed project are to: 1) characterize the deleterious effects of exogenous and endogenous cysteine proteinases catS and catK on bronchial epithelial cells in vitro, 2) determine whether SCCA1 and/or SCCA2 can protect cultured bronchial epithelial cells from the proteinase-mediated injury and isolate the target proteinases, 3) determine whether targeted expression of SCCA1 and SCCA2 can protect the airways from proteinase-mediated injury. The experimental design involves use of cell cultures in conjunction with stable transfections to overexpress SCCA1 and SCCA2. Barrier function of the airway epithelium will be studied by permeability and transepithelial resistance measurements as well as structural analysis. Affinity chromatography and co-immunoprecipation will be used to identify the target proteinases of SCCA1 and SCCA2 in proteinase-mediated injury in vivo. The rat clara cell 10kD protein promoter (CC10) will be used to target expression of SCCA1 and SCCA2 genes to the lung. Animals will be examined to determine the extent of protection against proteinase-mediated lung injury following exposure to acrolein. These studies should enhance our understanding of the mechanisms of
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proteinase mediated injury and whether the locally synthesized inhibitors such as SCCA1 and SCCA2 can prevent this type of damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOPOIETINS ANGIOGENESIS
IN
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Principal Investigator & Institution: Mcdonald, Donald M.; Professor of Anatomy; Cardiovascular Research Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 05-APR-1998; Project End 30-JUN-2006 Summary: (provided by applicant): The renewal of this project will examine the effects of angiopoietins, a recently discovered family of endothelial cell-specific growth factors, on blood vessel leakiness and vascular remodeling in airway inflammation. The project will build on the discovery made during the first two and a half years of this grant that angiopoietin-1 (Ang1) reduces plasma leakage evoked by multiple different inflammatory mediators. Ang1 also triggers the enlargement of venules in the airway mucosa but not elsewhere in the body. These actions, which are mediated by Tie2 tyrosine kinase receptors on endothelial cells, contrast with the formation of abundant leaky blood vessel by VEGF (vascular endothelial growth factor), another endothelial cell-specific growth factor. The project will test the overall hypothesis that the amount of plasma leakage and the type of microvascular remodeling in chronic airway disease are determined by the balance of growth factors such as Ang1 and VEGF acting on the vasculature. The project has three specific aims. (1) First, we will determine the mechanism and magnitude of the anti-plasma leakage effect of Ang1 on airway blood vessels. Our hypothesis is that this action of Ang1 results from the inhibition of endothelial gap formation through stabilization of vessel walls and intercellular junctions. (2) Second, we will examine Ang1-induced remodeling of the microvasculature in the airways. Here, the hypothesis is that Ang1 increases the caliber of venules in the airway mucosa because of the high density of Tie2 receptors on these vessels coupled with the survival factor action of Ang1 on endothelial cells of this intrinsically dynamic vasculature. (3) Third, we will develop a more complete understanding of the interplay between Ang1 and VEGF on microvascular leakage and angiogenesis. These experiments will test the hypothesis that Ang1 can reduce VEGFinduced vessel leakiness without blocking angiogenesis. The studies will also address the question of whether Ang1 can normalize the structure and function of angiogenic blood vessels formed in response to VEGF by stabilizing and maturing the vessel wall and strengthening intercellular junctions. The research plan provides an opportunity to gain insight into key growth factors involved in the regulation of vascular permeability and vascular remodeling in airway inflammation. Furthermore, elucidation of the protective effect of Ang1 on blood vessel leakiness would raise the possibility of a new strategy for reducing airway edema in chronic inflammatory diseases such as bronchitis and asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 2001; Project Start 16-AUG-1999; Project End 30-JUN-2004
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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 •
Project Title: ASSESSING THE OCCUPATION BURDEN IN COPD Principal Investigator & Institution: Blanc, Paul D.; Professor of Medicine; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (From applicant's abstract): The aims are to assess the population burden of occupational exposures in the prevalence of chronic obstructive pulmonary disease (COPD) and to estimate the impact of selected occupational risks on the severity of progression of COPD. COPD is common and costly. The contribution of occupational risk factors to its prevalence and progression have not been well characterized. Better delineation of these associations has been identified as a priority area for study in the NIOSH National Occupational Research Agenda. A population sample of the continental United States of those aged 55-75, supplemented by an enriched sample in geographic "hot spots" identified by NIOSH through respiratory diseases mapping, will yield 2120 subjects, of whom 400 will have COPD defined by report of chronic bronchitis or emphysema without asthma. Structured telephone interviews will assess demographics, health status, smoking exposures, and occupational histories. High risk jobs will later be coded using a job matrix system independent of subject report of specific exposures. Two hundred of those with COPD, with over-sampling of those with
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greater severity, will be followed at 12-14 months to assess health status and health services utilization, as well as decrements in quality of life. This study will provide statistically powerful estimates of the occupational association with COPD. We should be able to identify a work-related RR of 1.35 which, coupled with an exposure frequency of 20 percent, would reflect a PAR percent of 6.5 percent. In the longitudinal study component, we should be able to detect a RR>2.1 for selected occupational risk factors as predictors of outcomes occurring in at least 10 percent of the group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGY OF H INFLUENZAE HIA AND HSF ADHESINS Principal Investigator & Institution: St Geme, Joseph W.; Associate Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 15-DEC-1998; Project End 30-NOV-2003 Summary: Haemophilus influenzae is common cause of localized respiratory tract disease, including otitis media, sinusitis, bronchitis, and pneumonia. Less commonly, this organism causes serious systemic disease, such as meningitis, endocarditis, and septicemia. The initial step in the pathogenesis of H. influenzae disease involves colonization of the upper respiratory mucosa. We have identified a high-molecularweight protein called Hia, which is present in nontypable (nonencapsulated) H. influenzae and promotes attachment to human epithelium. In addition, we have identified a homolog of Hia called Hsf, which is univerally present among encapsulated H. influenzae and also mediates in vitro adherence. Interestingly, Hia has a predicted molecular mass of approximately 114 kDa and is not detectable by coventional transmission electron microscopy, while Hsf has a predicted molecular mass of approximately 245 kDa and is associated with the presence of short, thin surface fibrils visible by negative staining electron microscopy. Based on our in vitro results, we speculate that Hia and Hsf are important colonization factors. In the present proposal, we plan to characterize the pathway by which Hia and Hsf are localized on the surface of the organism. In particular, we will define the structural features of these proteins that direct them to the periplasm and facilitate their translocation across the outer membrane. We will dissect the influence of an unusual N-terminal extremity, a Cterminal domain predicted to form a beta-barrel, and a putative ATP-binding motif. In additional studies, we will examine the architecture of Hia and will investigate the relationship between structure and adhesive activity, focusing in particular on the role of a predicted coiled coil motif. We will also determine whether Hia and Hsf function interchangeably in an encapsulated strain. From a practical perspective, the results of these experiments may facilitate efforts to develop a vaccine protective against non-type b H. influenzae and suggest targets for novel antimicrobials with activity against a broad range of gram-negative bacteria. More generally, they may provide fundamental insights into the biogenesis of non-pilus adhesins and the nature of the host-microbial relationship. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGY OF SUBMUCOSAL GLAND STEM CELLS IN THE AIRWAY Principal Investigator & Institution: Engelhardt, John F.; Associate Professor; Anatomy and Cell Biology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAY-1990; Project End 30-APR-2005
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Summary: The identification of airway stem cells is a critical aspect in the development of gene therapies for diseases such as cystic fibrosis (CF). Furthermore, the complexities of disease pathophysiology in CF have suggested that submucosal glands may be important therapeutic targets. One approach to target this region, which is inaccessible from the airway lumen, is to facilitate gene transfer to airway stem cells responsible for submucosal gland development in utero. However, at present little is known about the biology of these stem cell targets in the airway. To this end, we propose to characterize the cellular phenotype of airway stem cells using molecular approaches that evaluate critical aspects of gene regulation important in the formation of submucosal glands. Experiments will attempt to identify and characterize the developmental pathways leading to stem cell commitment in submucosal gland morphogenesis. Such developmental mechanisms likely also play important roles in other hypersecretory diseases such asthma and chronic bronchitis, where submucosal gland hyperplasia and/or hypertrophy occur. Previous studies by this laboratory using retroviral based lineage analysis in the airway have suggested that a pluripotent surface airway epithelial stem cell compartment also has the ability to form submucosal glands. However, relatively little is currently known about the molecular phenotype of these airway stem cells. We will evaluate in detail the regulation of one particular gene, lymphoid enhancing factor-1 (Lef-1), a transcription factor known to regulate cell-fate decisions in other tissues. Recently we showed that activation of Lef-1 gene expression defines an airway progenitor/stem cell compartment at the earliest stages of epithelial commitment to form submucosal glands (ie., epithelial condensation involved in gland bud formation). Using Lef-1 as a molecular marker for this stem cell compartment, we propose to delineate pathways and transcription factors involved in its regulation using ferret and transgenic mouse models of the airway. Detailed analysis of the Lef-1 promoter will be performed using novel in vivo based model systems that include both recombinant gutted adenoviral vectors, as well as more traditional approaches involving transgenic mice. Lastly, this proposal will also attempt to evaluate mechanisms of Lef-1 action in submucosal gland morphogenesis. Of specific interest is the pathway involving wnt activation of beta-catenin, which is known to be a co-factor for Lef-1 in some, but not all, tissues. We will evaluate a possible role for the wnt pathway and beta-catenin in submucosal gland development using a novel airway specific transgenic mouse model expressing Lef-1 mutants incapable of binding with beta-catenin. Ultimately, this project will increase our understanding of stem cell phenotypes in the airway that have pluripotent capacity for submucosal gland development. Such information will undoubtedly be useful in the development of gene therapies targeting airway stem cells and submucosal glands. Additionally, an increased understanding of submucosal gland developmental mechanisms may provide new therapeutic approaches for treating submucosal gland hyperplasia and hypertrophy in hypersecretory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BTP1000 & THE CLEARANCE OF MUCUS FROM THE LUNGS Principal Investigator & Institution: Yeates, Donovan B.; Research Professor; Biotechplex Corporation 755 Nicholas Blvd Elk Grove Village, Il 60007 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 16-OCT-2003 Summary: (provided by applicant): Patients with chronic bronchitis, bronchiectasis, cystic fibrosis, asthmatic bronchitis and asthma have inspissated mucus and plugs of highly viscoelastic mucus. The inability to clear this mucus leads to impaired airway function and gas exchange and consequent morbidity and mortality. Present
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pharmacological therapies to treat such abnormalities, although widely applied in clinical practice, are inadequate and many have little or no scientific basis. BioTechPlex proposes to demonstrate the mechanisms of action and efficacy of a new therapeutic regime (BTP1000) to hydrate the airways and enhance mucociliary clearance. The specific aim of this Phase I project is to provide the preliminary data to support the novel intracellular mechanisms underlying the rationale for the use of BTP 1000 to increase airway hydration and ciliary beat frequency; factors that can be predicted to increase the clearance of secretions from the lungs. BioTechPlex will utilize its in-depth expertise in the mechanisms governing ion and water transport across epithelium and ciliary activity as well as its advanced technologies for the investigation of these airway epithelial functions. In the Phase II project the mechanisms of action of BTP1000 will be further expanded, validated and shown to substantially increase bronchial mucociliary clearance in dogs with minimal side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD11B/CD18 AND NEUTROPHIL EPITHELIAL INTERACTIONS Principal Investigator & Institution: Parkos, Charles A.; Associate Professor, Director; Pathology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 05-APR-1995; Project End 29-FEB-2004 Summary: Many inflammatory diseases of mucosal surfaces are characterized by transepithelial migration of neutrophils (PMN). Examples of such diseases are common in the gastrointestinal system (ulcerative colitis, Crohn's disease), respiratory tract (bronchial pneumonia, bronchitis), and urinary tract (pyelonephritis, cystitis). Accumulation of neutrophils within the lumenal spaces of these organs is associated with epithelial injury and correlates with disease symptoms. Despite a wealth of evidence supporting a central role of PMN in epithelial dysfunction in these diseases, the mechanism(s) of leukocyte interaction with mucosal remains poorly defined. In this proposal, our studies will focus on defining the molecular basis of leukocyte interactions with epithelial cells. Previously, we have shown that PMN transepithelial migration requires specific regions of the neutrophil beta2 integrin CD11b/CD18 and is independent of selectins and ICAM-1. Furthermore, we identified CD47 as an additional crucial component of the transepithelial migration response. However, the precise molecular details of these adhesive events and the nature of the epithelial counterreceptors for migrating PMN remain undefined. The overall goals of this proposal are to identify and characterize key adhesive interactions between neutrophils (PMN) and epithelial cells that serve to regulate the process of PMN transepithelial migration. Recently, a novel immunoglobulin superfamily member termed junction adhesion molecule (JAM) that is concentrated at cell-to-cell borders (intercellular junctions) of murine endothelium and epithelium was shown to participate in monocyte transmigration across mouse endothelium. In Specific Aim 1, we will extend our primary characterizing of the human homolog of JAM to define its role in PMN interactions with epithelial cells. In Specific aim 2, we will define the mechanism of how a novel epithelial mAb inhibits PMN migration and continue to produce others that inhibit the PMN transmigration response. Specific aim 3 will focus on the identification of specific epithelial receptors for CD11b/CD18 using monoclonal antibodies. Lastly, Specific aim 4 will employ random peptide phage display to identify peptide ligands for CFD11b/CD18 that modulate PMN-epithelial adhesion, Information from these studies will lead to a better understanding of the molecular events involved in PMN interactions with epithelial cells and may provide new ideas for therapeutic strategies aimed at attenuating inflammatory diseases of mucosal surfaces.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD14 AND LPS-INDUCED INFLAMMATION IN CHRONIC BRONCHITIS Principal Investigator & Institution: Peden, David B.; Professor of Pediatrics and Center Direc; Pediatrics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-AUG-2004 Summary: (adapted from the applicants' abstract) Chronic bronchitis and COPD are characterized by chronic neutrophilic inflammation and is associated with both airway sepsis with gram-negative bacteria. Smoking is a major risk factor for development of these diseases, but only about 20 percent of smokers develop COPD. Endotoxin (ET) from gram- negative bacteria likely plays a significant role in this inflammation. Airway ET may come directly from gram-negative bacteria infecting the airway or from tobacco smoke as this is another rich source of ET. The investigators propose that responsiveness to ET also an important risk factor for development of COPD in smokers. One mechanism by which persons may be more sensitive to ET is by enhanced production of CD14, the primary receptor for ET. CD14 exists in both a cell bound form and as a soluble from in serum and airway secretions. Soluble CD14 in the airway is enhanced by acute allergic inflammation. Additionally, a C/T polymorphism has been identified at the - 159 position of the CD14 promoter gene (CD14 gene). Those persons homozygous for the T allele have been shown to have increased soluble CD14 in serum and CD14 expression on blood monocytes compared to those with CT or CC genotype. The investigators present preliminary data that demonstrates that levels of sCD14 in sputum and CD14 expression on alveolar macrophages prior to challenge with lipopolysacharride (LPS, a form of ET) correlates with neutrophil influx in sputum following inhaled LPS challenge. Also, in the nasal airway, allergen enhances granulocyte response to LPS in a fashion which correlates with local sCD14 levels. The investigators propose to examine the role that CD14 has in determining responsiveness to airway LPS and risk for COPD in smokers. First, the investigators will determine if the level of sCD14 and CD14 on macrophages is increased in volunteers with experimentally-induced and naturally occurring bronchitis and if they have increased neutrophil response to LPS. Second, the investigators determine if airway CD14 correlates with PMN response to LPS in normal volunteers. Third, the investigators will determine if airway CD14 levels and LPS response in healthy volunteers with the TT genotype for the CD14 gene is enhanced relative to that in those with the CC and CT genotype. Finally, the investigators will genotype cohorts of COPD patients and healthy smokers to determine if the T allele is a risk factor in development of COPD in those who smoke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 2001; Project Start 16-JUL-2001; Project End 30-JUN-2006 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 anti-
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donor 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 •
Project Title: CHARACTERIZING A 5P-LINKED BHR SUSCEPTIBILITY LOCUS Principal Investigator & Institution: Ober, Carole; Professor; Human Genetics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) Asthma is the most common chronic disease in industrialized nations, affecting >10 million people in the U.S. alone. Familial aggregation and concordance rates in monozygotic twins have suggested a genetic component to asthma. We have been conducting studies on the genetics of asthma and atopy in the Hutterites, a founder population of European origins that practices a communal lifestyle. A genome-wide screen with 564 markers (average spacing 6 cM) was completed in an extended pedigree of 717 Hutterites who were well characterized with respect to asthma, atopy, and related phenotypes. These individuals are descendants of only 64 ancestors who lived in the early 1700's to the early 1800's. Evidence for linkage with bronchial hyperresponsiveness2 (BHR) by the likelihood ratio test extended over 30 cM on chromosome 5p, with P-values as small as 0.001. Additional evidence for linkage at this same location was evident by the transmission disequilibrium test (P=0.0061). Typing additional markers in this region identified a critical region of 2.4 cM, corresponding to 1.5 Mb of DNA, and a high risk haplotype that is over transmitted to affected individuals. In this application, we propose to characterize the 5p-linked BHR susceptibility locus in the Hutterites by positional cloning and to replicate these findings in outbred, ethnically diverse populations. We will examine single nucleotide polymorphisms (SNPs) spaced about 10 kb apart in each gene, and assess the evidence for over transmission to affected offspring with each SNP and SNP haplotypes. Associations in the Hutterites will be replicated in the outbred samples. The functional effects of associated variants will be assessed by in vitro assays as well as by genotype-phenotype studies in outbred samples that have been evaluated for asthma and atopy phenotypes. Identifying asthma or BHR susceptibility loci may identify novel pathways in asthma pathogenesis, thereby allowing for the development of new therapies and intervention strategies for these common diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMOKINE BIOLOGY IN BRONCHIOLITIS OBLITERANS SYNDROMEN Principal Investigator & Institution: Belperio, John A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; 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, 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
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Project Title: CHEMOKINE/ CYTOKINE CONTROL OF EOSINOPHIL LUNG DAMAGE Principal Investigator & Institution: Heiman, Ann S.; Florida Agricultural and Mechanical Univ Tallahassee, Fl 32307 Timing: Fiscal Year 2001; Project Start 05-JUN-2000; Project End 30-APR-2005 Summary: Asthma is defined as a chronic inflammatory disorder of the airways. Recurrent exacerbations that characterize the disordered lung function in asthma are associated with an increased inflammatory response. As described by the Global Initiative for Asthma, it effects an estimated 7% of the U.S. population, occurs among all ages and is significantly increasing in prevalence, cost of care, morbidity and mortality.
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It is well- accepted that airway diseases are characterized by an underlying inflammation in which many cells, particularly eosinophils (EOS), play a role. Once recruited and activated, EOS have the capability of synthesizing and releasing numerous pro-inflammatory mediators into the pulmonary microenvironment. Most asthmatics, even those with mild disease, show substantial chronic desquamating, eosinophilic bronchitis. This inflammation plays a role in disease pathogenesis since it contributes to bronchoconstriction, swelling of the airway wall and airway remodeling. Considering these airway diseases as inflammatory disorders has implications for diagnosis, prevention and therapeutic management. The focus of these proposed investigations is treatment of the underlying EOS-mediated inflammation, thus preventing permanent destruction of lung tissue. The overall objective of these proposed investigation is to identify EOS-selective cytokine(s) or chemokine(s) which may serve as therapeutic targets to decrease EOS recruitment, adhesion, inflammatory mediator release and delayed apoptosis and test these identified cytokines as candidates for an antisense oligonucleotides treatment approach. Experiments will be designed to explore the hypotheses that: EOS-selective cytokines increase pro-inflammatory mediator release and adherence of EOS to airway epithelial cells (specific aim 1), the airway epithelium is a paracrine source of EOS-active cytokines (specific aim 2), EOS apoptosis can be induced without release of pro-inflammatory mediators (specific aim 3), and antisense oligonucleotides can be used as an adjunctive therapeutic approach to specifically suppress expression of genes which direct the pro- inflammatory activities in EOS (specific aim 4). Understanding processes which control selective eosinophilia is an important prelude to development of more effective therapies for a variety of human diseases including asthma and allergies. Results of this research may assist in fulfillment of the priority research needs on effects of pharmacological treatment and immunotherapy in the long-term management of asthma as outlined by the Global Initiative for Asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOKINES IN LUNG TRANSPLANTATION Principal Investigator & Institution: Medoff, Benjamin D.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): With the proposed Mentored Clinical Scientist Development Award the applicant will continue his investigations into basic mechanisms of lung inflammation. After two productive years in this laboratory the applicant remains firmly committed to a career in academic pulmonary medicine. The proposed research will allow the applicant to master a broad range of laboratory techniques in immunology, cell, and molecular biology. The research experience will be supplemented by a program of study of immunology and medical science. The project focuses on the development of inflammation and fibrosis following lung transplantation and the role of chemokines in these processes. After a lung is transplanted there may be several types of injury to the graft, including ischemia-reperfusion injury, acute rejection, and chronic rejection. These immune mediated injuries contribute to the development of scarring of the airways, so called bronchiolitis obliterans (BO). Over 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
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and their contribution to the development of graft injury and subsequent BO. Further experiments will manipulate chemokine or chemokine receptor expression in animal models of lung transplantation to investigate their role in the development of graft injury and BO. The applicant specifically proposes to: (1) investigate the expression of chemokines and chemokine receptors in the lung following transplantation in patients with and without acute rejection and BO; (2) investigate the role of chemokines in the development of ischemia-reperfusion injury in the airways using the murine tracheal heterotopic model of lung transplantation; (3) investigate the role of chemokines in the development of acute airway rejection and the development of BO in the murine tracheal heterotopic model of lung transplantation; (4) develop a novel murine model of airway rejection and BO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHLAMYDIA SIGNIFICANCE
PNEUMONIAE
ANTIGENS
OF
BIOLOGICAL
Principal Investigator & Institution: Campbell, Lee A.; Professor; Pathobiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2007 Summary: (provided by the applicant): Chlamydia pneumoniae is a human respiratory pathogen that causes 5 percent to 10 percent of pneumonia, bronchitis, and sinusitis. Virtually everyone is infected in his or her lifetime and reinfection is common. Infection is difficult to treat even with sensitive antibiotics. Chronic infection is common and has been associated with asthma, reactive airway disease, Reiter's syndrome, erythema nodosum, and sarcoidosis. The potential public health impact of infection with this pathogen is underscored by the association of C. pneumoniae with atherosclerosis and related clinical manifestations such as coronary heart disease, carotid artery stenosis, aortic aneurysm, claudication, and stroke. If C. pneumoniae infection plays a role in atherogenesis, there will be an urgent need to facilitate diagnosis and develop strategies for intervention and prevention. The overall goal of this proposal is two fold. First, C. pneumoniae specific antigens that are recognized during human infection will be exploited to facilitate serodiagnosis and identify putative vaccine candidates. The second goal is to define chlamydial/host cell interactions that lead to entry and survival of C. pneumoniae in host cells relevant to atherosclerosis. The specific focus will be on the interaction of the chlamydial glycan moiety with carbohydrate binding receptors on the host cell. Importantly, infection of epithelial cells can be inhibited with N-linked high mannose type oligosaccharide, the major component of the glycan. The novel hypothesis to be tested is that C. pneumoniae enters through the mannose-6 phosphate receptor by binding to the site involved in transport of phosphomannosylated residues to the lysosome and this differs from C. trachomatis, which utilizes the mannose receptor. The ultimate goals of these studies are to identify C. pneumoniae specific antigens to facilitate laboratory diagnosis and virulence factors playing a role in pathogenesis to guide vaccine development or develop anti-adhesive strategies for prevention of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC LOCALIZATION
OBSTRUCTIVE
PULMONARY
DISEASE
GENE
Principal Investigator & Institution: Hasstedt, Sandra J.; Associate Professor; Human Genetics; University of Utah 200 S University St Salt Lake City, Ut 84112
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Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Applicant's Abstract): Chronic obstructive pulmonary disease (COPD) is a slowly progressive disorder characterized by airways obstruction that lasts for at least several months. The two major causes of COPD are chronic bronchitis and emphysema. Either disorder may occur with or without airways obstruction, but airways obstruction causes impairment of lung function leading to disability and death. COPD is a major health problem in the United States and throughout the world, consistently ranking among the most common causes of death in the United States. Cigarette smoking is the primary environmental factor that increases the risk of COPD, but other environmental factors have also been implicated. However, despite a well-established role, environmental factors alone do not cause COPD. Symptomatic COPD develops in only 10-20 percent of heavy cigarette smokers, probably those with a genetic susceptibility, although common COPD susceptibility genes have yet to be identified. This project proposes a single specific aim: to localize, within the genome, a COPD susceptibility gene. The strategy proposed is to apply statistical linkage analysis to family data. Pulmonary measurements have already been collected on 159 members of 16 pedigrees and evidence supporting a COPD susceptibility gene in these pedigrees has been obtained from segregation analysis. Each of 11,995 genetic markers, which have already been genotyped on pedigree members, will be tested for evidence of linkage to the inferred COPD susceptibility gene. Evidence of linkage to one or more genetic markers will identify genomic locations of COPD susceptibility genes. The high density of markers will allow fine-mapping of the gene. Successful completion of this gene localization project is the necessary prerequisite for a project to identify and characterize a COPD susceptibility gene. Identifying a gene that when mutated increases the risk of COPD may increase understanding of pulmonary function, as well as allowing genecarriers to be identified and made aware of their susceptibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--EXPOSURE FACILITY Principal Investigator & Institution: Spengler, John; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: The Exposures Facility Core has seven components: 1) Organic chemistry laboratory, 2) Inorganic chemistry laboratory, 3) Microbiology laboratory Particle measurements (aerosol properties) laboratory, 4) Metal analysis laboratory, 5) Radiation laboratory, 6) Inhalation laboratory. The aims of this core are to maintain the analytical equipment, to facilitate quality control/quality assurance programs, to provide staff and Center faculty with flexibility to develop/adopt analytical methods, and to provide training and supervision to students, postdoctoral fellows, and visiting scientists. All laboratories have written standard operating procedures and quality assurance programs, many of which include interlaboratory testing. The organic chemistry laboratory has analyzed breast milk and cord blood samples for PCBs as part of a study of the effect of low levels of PCBs on reproductive outcomes in New Bedford, and this work will be extended to examine reproductive effects of PCBs in a Russian city contaminated by PCBs. They have also participated in several interlaboratory studies. The inorganic chemistry laboratory has developed an annular denuder system and methods for studying acidic aerosols and gases, ammonia, and passive and active ozone samplers. The environmental microbiology laboratory has developed methods for assessing fungi, bacteria, endotoxin and allergens in bulk dust and air samples. The aerosol properties laboratory specializes in the generation and characterization of
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particles. The laboratory has developed an ambient particle concentrator for use in animal and human exposure studies. Work is currently in progress on determining the partitioning between gas and particle phase of semi-volatile organic compounds. The metals/aquatic laboratory has studied samples of metal exposures of workers, in sediments and biota of Boston and New Bedford harbors, and in water along the USMexican border, and arsenic in the toenails of Taiwanese as part of a study of bladder and skin cancer. A future project will study the bioavailability of heavy metals in contaminated marine sediments. The radiation biology laboratory has several unique radiation sources, including an X-ray generator, an high intensity cobalt source, and an irradiation chamber for animals. Members of the Biochemical and Environmental Toxicology and the Radiobiology and Environmental Carcinogenesis Cores have used these devices to produce "feed layers" of cells for studies of the growth of differentiated cells an tissues in vitro and in studies of DNA damage and repair. The inhalation laboratory provides researchers with the facilities and technical expertise to expose animals to various types of air pollutants, including ozone, sulfur dioxide, particles, fly ash, ethylene oxide, and cigarette smoke, and to monitor their pulmonary responses, including ventilatory parameters and pulmonary mechanics, to these exposures. Studies conducted include the examination of various mechanisms or markers of ozone induced lung injury, the role of adhesion molecules and ctytokines in epithelial injury and repair, the role of sensory neuropeptides found in C-fibers in ozone-induced lung injury and altered airway responsiveness, and the use of SO2 exposure to generate animal models of chronic bronchitis. The mechanisms of mortality and morbidity associated with urban exposure to particles is being studies by exposing dogs and rats to concentrated ambient particles. Future plans include evaluation of the role of adhesion molecules in the airway hyper-responsiveness characteristic of ozone exposure, and further work on the development of biomarkers of ozone exposure. Physiologic responses, e.g., measures of ventilation, to inhaled gases or particles can be monitored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOXICOLOGY
CORE--RESPIRATORY
BIOLOGY
AND
INHALATION
Principal Investigator & Institution: Brain, Joseph D.; Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: The Respiratory Biology and Inhalation Toxicology (RBIT) Core has as its objective "to understand how breathing results in environmental and occupational lung disease." The core seeks to develop prevention strategies and more effective treatments for pulmonary diseases including lung cancer, asthma, pulmonary fibrosis, and emphysema. The RBIT Core is primarily concerned with the effects of inhaled environmental toxicants on the mammalian pulmonary system. The Respiratory Biology and Inhalation Toxicology Core is involved with five primary lines of investigation. First, they have investigated the mechanisms of particle binding to alveolar macrophages and epithelial cell lines. Their data suggest that the macrophage scavenger receptor system is responsible for the binding of charged particles such as latex beads and titanium dioxide as well as quartz, fly ash and urban air particulates. This system did not appear to be operative in A549 epithelial cell lines. They now wish to pursue studies of the calcium concentration dependency of this binding and inhibition of this binding by scavenger receptor ligands. They have determined that appropriately-raised polyclonal antibodies block particle binding. Thus, they would like to investigate the molecular biology of this further using scavenger receptor knock out mice and
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expression cloning of blocking antibodies. Lastly , they plan to study the effects of mitochondrial oxidant production on cytokine release upon exposure to quartz versus titanium. The second line of investigation seeks to elucidate the mechanism of the epidemiologic finding that mortality of cardiovascular etiology is elevated about 24 hours after peaks in the concentration of urban air particulates (PM10). To carry out these studies they have used the ambient air particle concentrator (a series of virtual impactors) built by Sioutas and Koutrakis, et al. to generate concentrated urban air aerosols from Boston ambient air. Animal models (dogs, rats, and mice) are used that attempt to recreate the susceptibility factors that are associated with mortality during urban air inversions. Included are a chronic bronchitis model, various knock out mice, and dogs with induced cardiac ischemia. The third research interest concerns the physiology and biology of airway hyper-responsiveness. This group has worked extensively with a technique that measures the stiffness of smooth muscle cell cytoskeleton by manipulating and measuring the effects of cytoskeleton-bound ferromagnetic spheres on magnetic fields. This technique allows Respiratory Biology and Inhalation Toxicology Core investigators to test the effects of cytokines or pharmacologic agents on the contractility of airway smooth muscle cells. They are also interested in developing mouse models for allergic inflammation and airway hyperresponsiveness. They describe their fourth area of research interest as the development and application of bioassays for lung injury. For the most part this appears to be an effort to bring published assays into the laboratory s repertoire. Assays include lavage cytokines, enzymes, proteins, and message for several mediators. The last area of investigation described for the Respiratory Biology and Inhalation Toxicology Core is studies of the molecular mechanisms of pulmonary inflammation. In this work the investigators are considering signal transduction pathways for lung cell adhesion and the dynamics of neutrophil migration into the lung. They are also investigating the cells and chemokines that trigger the release of reactive oxygen species. In particular, they have studied rat MIP-1 alpha and MIP-2, a neutrophil chemotactic chemokine. Within these research studies is evidence of collaboration between the Respiratory Biology and Inhalation Toxicology Core and several other cores and facilities within the Center. Most notable are the Environmental Epidemiology Research Core and the Toxicology Research Core although there is reference to the Occupational Health Core and the Environmental Sciences and Engineering Core as well. The Respiratory Biology and Inhalation Toxicology Core investigators rely on a number of facilities for equipment and expertise. A central molecular biology laboratory provides nucleic acid and protein sequencing, PCR, in site hybridization and immunocytochemistry. Tissue and cell culture facilities are maintained within the Physiology Program. The Bioimaging Core provides laser scanning, confocal microscopy and morphometrics capabilities. The two electron microscopy laboratories offer scanning and transmission electron microscopy with electron specrtoscope imaging capabilities. An inhalation toxicology laboratory has three 1m3 Lucite chambers and two 100 l Lucite chambers. They are primarily set-up for the generation of gases (ozone and So2) and for concentrated Boston ambient air particles. The Respiratory Biology and Inhalation Toxicology Core is equipped with devices for blood and gaseous phase gas analysis and devices for respiratory mechanics and electrophysiology. Lastly, the core has developed a device for magnetometry in order to study changes in cytoskeletal stiffness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CTRS FOR EDUCATION AND RESEARCH ON THERAPEUTICS (CERTS) Principal Investigator & Institution: Strom, Brian L.; Professor of Medicine and Pharmacology; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: There remain enormous gaps in the information available to the public about the effects of their drugs, and in the application of that information to optimizing prescribing and thereby improving the risk/benefit balance from drugs. Centers for Education and Research on Therapeutics (CERTs) offer the opportunity to address many of these deficits, and this proposal goes a long way toward filling that gap. In particular, we propose to: 1. Establish a CERT with a coordinated infrastructure, including: a. Logistical support, including faculty time and core staff; b. Governance, including regular coordination and business meetings; c. Programmatic coordination, including linkage of the pharmacoepidemiology skills of the Center for Clinical Epidemiology and Biostatistics (CCEB) with the pharmacoeconomics skills of the Leonard Davis Institute of Health Economics, the experience in patient -oriented research of the General Clinical Research Center; basic science laboratories interested in evaluating the molecular mechanisms of drug effects; and the social science skills of non-biomedical researchers in other parts of the University; d. Regularly scheduled educational conference series; e. Active participation in the national network of CERTs; and f. A pilot research grant program targeted at the development of R01 quality grants and proposals. 2. Testing and building the capabilities of the current Penn ambulatory drug use evaluation program as a laboratory, expanding it to broader populations; 3. Improve the use of antibiotics locally and nationally, with studies leading to grant funding for larger scale efforts, as well as formal dissemination of evidence-based data both known and to be known. The initial studies will: a. evaluate techniques to reduce the use of antibiotics for acute bronchitis in the outpatient setting b. evaluate the impact of antimicrobial formulary interventions at different hospitals on the resistance patterns of extendedspectrum beta-lactamase- producing Escherichia coli and Klebsiella species; c. simulate data, in order to expand the use of meta-analysis to study rare adverse outcomes from antibiotics; d. study the effects of tetracycline used to treat acne in a dermatology clinic on antibiotic resistance patterns; and e. study the use of the GPRD Database to explore the epidemiology of drug -resistant pneumococcal pneumonia 4. Conduct an extensive education program, including: i) a Masters in Clinical Epidemiology (MSCE) and PhD pharmacoepidemiology fellowship training program; ii) opportunities for MSCE and PhD students in epidemiology and biostatistics to use existing in-house databases to answer new questions, to participate in ongoing research, and to develop new research projects; iii) courses for university physicians housestaff, nurses, and nursing students; iv) courses for pharmacists and pharmacy students; v) courses for medical students; and vi) a degree credit course in pharmacoepidemiology for MSCE students. 5. Organize and formally disseminate the results of our work, consisting of: publications and presentations for the Scientific/Professional community; ii) the FDA, AHCPR, other CERTs, etc.; and iii) the public, building on the dissemination program of the Leonard Davis Institute of Health Economics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOSE RESPONSE MODELING IN EPIDEMIOLOGIC COHORT STUDIES Principal Investigator & Institution: Eisen, Ellen A.; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: This proposal addresses the problem of nonlinear dose response estimation in environmental and occupational cohort studies by exploring two more flexible regression strategies: Generalized Additive Models (non-parametric regression) and a nonlinear dose metric. Typically, dose response models assume that the relationship is linear on some scale. Many disease mechanisms, however, such as sensitization or carcinogenesis, may produce nonlinearities in the dose-response curve. Moreover, linear models may be inappropriate in occupational cohort studies where the healthy worker effect can lead to an apparent plateau or even downturn in risk among the more highly exposed. General additive models will be used to describe the shapes of the doseresponse curve between cumulative exposures and selected outcomes in three cohort mortality studies with well established exposure response associations. The three data sets available for dose-response modeling are: 46,400 autoworkers exposed to metalworking fluids, 5,414 Vermont granite workers exposed to silica in quartz form and 2,342 diatomaceous earth miners exposed to crystalline silica in cristobalite form. Disease outcomes of interest will include cancers of the stomach, esophagus, pancreas, and liver in the metalworking fluid cohort, and cancer of the lung in the two silica cohorts. Nonmalignant respiratory disease mortality will be examined in all cohorts. In addition, we will apply a flexible dose model for metalworking fluids and crystalline silica that includes simple cumulative exposure as a special case. Unlike standard analyses that are limited to linear relations with cumulative exposure, this model, proposed by Seixas, is sufficiently flexible to enable investigation of nonlinear dose-rate effects and variable disease induction/latency intervals. Secondary objectives include the direct comparisons of the carcinogenicity of the four types of metalworking fluids (mineral oil, solubles, synthetic, and semi- synthetics) and of quartz and cristobalite polymorphs of crystalline silica. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INFECTION
EFFECT
OF
PARTICULATE
MATTER
ON
RESPIRATORY
Principal Investigator & Institution: Lambert, Amy L.; Ciit Centers for Health Research Po Box 12137 Research Triangle Park, Nc 277092137 Timing: Fiscal Year 2001; Project Start 16-NOV-2001 Summary: (provided by applicant):Epidemiologic studies have demonstrated that increased levels of particulate matter (PM) air pollution in the ambient air are strongly correlated with increased morbidity and mortality in exposed populations, chiefly in individuals with pre-existing cardiopulmonary disease. Particle size contributes to these adverse health associations, and PM with an aerodynamic diameter of < 1.0 um (ultrafine PM) is thought to be the most toxic. Increased incidence and severity of symptoms associated with asthma and lower respiratory infections, such as wheezing, bronchoconstriction, and cough have been reported in children and older adults following PM excursions. Respiratory syncytial virus (RSV) causes worldwide epidemics of respiratory disease each year, and commonly afflicts infants (6 months-1 year old), immuno-compromised individuals, and older adults (60+ years old). Severe RSV is strongly associated with wheezing, childhood asthma, and repeated episodes of
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bronchospastic bronchitis, which can continue into adulthood. The primary aim of this proposal is to examine the effect of ultra-fine PM on host defense to RSV infection. The overall hypothesis of this proposal is that individuals with pre-existing respiratory viral infection exposed to ultra fine PM have decreased host defenses and subsequent exacerbation of viral infection, including elevated pulmonary inflammation, lung function decrements, and reduced ability to clear the virus. A mouse model of RSV infection will be used to 1) Determine the effects of ultra-fine (UF) carbon black (CB) particles on the course of RSV infection in the lung and on pulmonary inflammation and lung function; 2) Determine the effect of UF CB exposure on immune cytokine expression by RSV infected bronchial epithelial cells; 3) Determine the role of PMinduced cytokine production by RSV-infected bronchial epithelial cells in host defense to RSV. These studies will address for the first time the effects of ultra-fine PM on pulmonary host defense to a viral infection in vivo, and will provide mechanistic information regarding the pathophysiology of viral disease following PM exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF CHINESE HERBAL MEDICINES ON ALLERGIC ASTHMA Principal Investigator & Institution: Li, Xiu-Min; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 30-NOV-2003 Summary: (provided by applicant): Allergic asthma is a major public health problem, and the morbidity and motility of asthma have increased in the last two decades, particularly in children. The need for safe and effective asthma treatment is greater than ever. Although millions of asthma patients in the US are currently using "herbal therapies," there is little information regarding the efficacy, safety or mechanism[s] of action of herbal anti-asthma formulas. It has been shown that allergic asthma is associated with elevation of serum IgE, airway inflammation and airway hyperresponsiveness (AHR) in both asthmatic patients and animal models. Th 2-type cytokines such as IL-4, IL-5 and IL-13 play a central role in the pathogenesis of allergic asthma. To investigate the effect of herbal interventions for asthma therapy, we evaluated effects of a Chinese herbal formula, MSSM-002, on allergic airway responses using a well-characterized murine model of asthma. MSSM-002, developed in our laboratory, is based on Ja Wai San Zi Tang, used in the China-Japan Friendship Hospital in Beijing, to treat asthma and bronchitis in children. We found that MSSM-002 treatment reduced late-phase AHR, eosinophilic inflammation, mucus production, and IgE and Th2 cytokine production. Suppression of late-phase AHR by MSSM-002 was comparable to that of the potent corticosteroid, dexamethasone, and significantly greater than three commercially available Ma-Huang-containing herbal products. These preliminary results suggest that MSSM-002 has potential as an effective and safe treatment for human asthma. The objective of this project is to further investigate the therapeutic and immunoregulatory mechanisms underlying these effects. We will evaluate whether MSSM-002 can reverse maximally severe AHR, and exert a long-term as well as an acute effect on AHR. We will rigorously control the quality of herbs and consistency of the herbal formula using reproducible analytic methods such as HPLC and TLC, and further assess any possible toxicity utilizing histological and biochemical analyses. Based on our preliminary results, we hypothesize that, in contrast to the generalized immunosuppression produced by corticosteroids, MSSM-002 has specific immunomodulatory effects down-regulating the Th2 response and/or up-regulating the Thl response, which may underlie the observed reduction of AHR and inflammation by
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MSSM-002. We will further investigate the effects of MSSM-002 on in vivo and in vitro T cell cytokine production. We further hypothesize that MSSM-002 may exert beneficial regulatory effect on co-stimulatory molecules such as B7-1/B7-2 by antigen-presenting cells, which may be the upstream mechanisms of MSSM-002 regulating T cell responses. To move our study one step closer to human studies, we also plan to test the in vitro effects of MSSM-002 on human T cell responses. Accomplishing these goals should provide an experimental basis for applying Chinese herbal medicines to the treatment of allergic asthma, and for understanding immunoregulatory mechanisms underlying their effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGIC STUDIES OF LUNG CANCER RISKS IN NSAID USERS Principal Investigator & Institution: Zheng, Wei; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 28-JUN-2001; Project End 31-DEC-2006 Summary: (provided by applicant): Cumulative evidence from in vitro and animal studies suggests that the enzyme cyclooxygenase-2 (COX-2) is important in the development and progression of lung cancer. Epidemiologic studies evaluating the association between the use of aspirin (an inhibitor of COX-2) and the risk of lung cancer have been conflicting, and no study has been conducted to evaluate non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). Using pre-recorded drug prescription databases of the Tennessee Medicaid program and North Jutland County of Denmark, we propose to conduct two studies in these populations to examine the effect of NSAID use on the risk of lung cancer. The first is a retrospective cohort study of over 10,000 enrollees of the Tennessee Medicaid Program who were diagnosed with chronic obstructive pulmonary diseases (COPD) during the period of 1980 to 2002. The second is a population-based, retrospective cohort study of over 150,000 users of NSAIDs in the general population of North Jutland County during the period of 1991 to 2002. Within the Danish cohort will be a nested case-control study of 350 cases and 700 controls, in which relevant information will be obtained on over the counter (OTC) analgesic use, as well as cigarette smoking and other potential confounding factors. The two studies proposed here complement each other and provide for an international comparison of NSAIDs as possible lung cancer chemoprevention agents. Because the data on NSAID use have already been collected, the studies will be very cost-efficient. More importantly, the use of pre-recorded pharmacy records minimizes potential errors in exposure assessment and provides a major advantage over existing cohort studies in evaluating the potential chemopreventive effect of NSAIDs. Given the high incidence and mortality of lung cancer and high prevalence of NSAID use, the results from our studies may have important public health implications in lung cancer prevention, and could set the stage for future randomized trials of COX-2 inhibitors in cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPITHELIAL CELL RESPONSE TO H.INFLUENZAE IN THE AIRWAY Principal Investigator & Institution: Look, Dwight C.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-JUL-2004
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Summary: (adapted from the application): Inflammation of the airway epithelium is often required for effective innate defense against microbes, and epithelial cells provide critical biochemical signals that regulate this response. One major mechanism that epithelial cells in the airway use to participate in the inflammatory response is through regulation of leukocyte trafficking and/or activation by expression of intercellular adhesion molecule-1 (ICAM-1). ICAM-1 serves as a ligand for leukocyte beta2-integrins and thereby mediates epithelial-leukocyte interactions that may allow for "appropriate" inflammatory responses (e.g., to a respiratory bacterial infection) or "inappropriate" responses (e.g., airway inflammation in cystic fibrosis). This proposal focuses on Haemophilus influenzae, which frequently colonizes human respiratory mucosa and often produces respiratory tract disease, particularly in patients with chronic bronchitis, bronchiectasis, and cystic fibrosis. The specific aims of this proposal are based on four observations regarding airway epithelial cell ICAM-1 expression in response to H. influenzae: 1) H. influenzae induces airway epithelial cell ICAM-1 expression in vivo and in vitro; 2) ICAM-1 expression is required for efficient bacterial clearance in a murine model of airway infection with H. influenzae; 3) increased ICAM-1 expression can be initiated by epithelial cell interaction with a constitutive molecule on the bacterial cell surface; and 4) airway epithelial cell interaction with H. influezae results in generation of soluble ICAM-1 inducing activity containing a novel mediator(s) of ICAM1 expression. Based on these observations, they hypothesize that direct induction of specific epithelial genes (such as ICAM-l) allow for rapid targeting and/or activation of neutrophils and other leukocytes at sites of H. influenzae infection, resulting in efficient innate defense in the airway. Accordingly, there are two specific aims. 1) Define mechanisms for induction of epithelial cell ICAM-1 expression by H. influenzae. This aim will take advantage of in vitro coculture models of epithelial cell interaction with bacteria. Definition of mechanisms for ICAM-1 gene activation in response to H influenzae will be accomplished by analysis of ICAM-1 promoter function and identification of mediator molecules. This latter refers to the observation that airway epithelial cells challenged with H. influenzae release a novel soluble factor into the medium capable of eliciting ICAM-1 in naive epithelial cells. 2) Determine functions of ICAM-1 in defense against H. influenzae infection. This aim will take advantage of in vivo murine models of airway infection by bacteria. The functions of ICAM-1 will be determined by examining ICAM-1 expression, leukocyte recruitment and function, and bacteria clearance under conditions that allow for manipulation of airway defense factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPITHELIAL CELLS IN LUNG INFLAMMATION Principal Investigator & Institution: Kao, Peter N.; Associate Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 29-FEB-2004 Summary: Excessive airway inflammation occurs in asthma, bronchitis and bronchiectasis. Local human bronchial epithelial (HBE) cells express chemoattractant cytokines and hematopoietic growth factors that serve to recruit immune effector neutrophils and lymphocytes, amplifying the airway inflammatory response. Molecular mechanisms regulating HBE cell expression of inflammatory cytokines will be elucidated. Stimulated HBE cells express substantial IL-8 and little IL-2, and stimulated T-cells express substantial IL-2 and little IL-8. This reciprocal expression of IL-8 and IL-2 in HBE and T-cells is regulated by transcription factors NF-kappaB and the CsAsensitive purine-box regulator. The CsA-sensitive purine-box regulator in HBE and T-
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cells binds to purine-rich DNA sequences including the IL-8 NF-kappaB site and the NFAT target site, and mediates sequence-specific transcriptional repression. Cell stimulation that mobilizes calcium triggers the conversion of the purine-box regulator from a repressor into a transcriptional activator: this conversion is most extensive in activated T-cells. The CsA-sensitive purine-box regulator in HBE and T-cells contains subunits, NF45, NF90, Ku70, Ku80, and the DNA-dependent protein kinase, catalytic subunit. The stimulation-induced structural changes in the purine-box regulator subunits which control the functional conversion from a repressor into a transcriptional activator will be identified, using immunoprecipitation, phosphopeptide mapping, and in vitro transcription experiments. The molecular mechanisms through which CsA and FK506 destabilize the purine-box regulator/NF-kappaB repressor and induce constitutive IL-8 secretion, will be elucidated. In related studies, the molecular mechanisms of action of a novel antiinflammatory drug, PG490 (triptolide), derived from a Chinese herbal remedy for arthritis, will be determined. PG490 inhibits NFkappaB transcriptional activation and inflammatory cytokine gene expression by epithelial cells and T-cells. A signaling enzyme in HBE cells which is specifically inactivated by PG490 and which regulates NF-kappaB transcriptional activation in the nucleus will be isolated and characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL MEDIATED CILIA MOTILITY DYSFUNCTION Principal Investigator & Institution: Sisson, Joseph H.; Professor; Internal Medicine; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 01-MAR-1991; Project End 31-JUL-2005 Summary: (Adapted from the applicant's abstract): Alcoholics have a high incidence of pulmonary diseases due to altered lung host defenses. A major airway defense function that is impaired during alcohol ingestion is mucociliary clearance, which is dependent on the coordinated beating of cilia that line the airways. Studies from this laboratory indicate that short term ethanol exposure stimulates ciliary motility through a nitric oxide-dependent mechanism that requires the activation of both cAMP- and cGMPdependent protein kinases (PKA and PKG). In contrast, chronic exposure to ethanol causes desensitization of ciliary motility such that the cell no longer responds to stimulation by beta-agonists. In this context we hypothesize that: Chronic ethanol exposure impairs airway ciliary responsiveness by downregulating NO-dependent protein kinase activity resulting in altered phosphorylation of cilia target proteins and impaired mucociliary clearance. The test this hypothesis experiments will befocused around four specific aims: 1) Characterize the differences in airway cell signal transduction between acute ethanol cilia stimulation and chronic ethanol cilia desensitization; 2) Determine the intracellular factor(s) that ethanol targets resulting in chronic ciliary desensitization; 3) Determine the phosphorylation targets in the cilia axoneme that ethanol mediates through protein kinase activation; and 4) Characterize the effects in vivo of acute and chronic ethanol exposure on airway kinase activation and ciliary responsiveness. The impact of alcohol-related respiratory illnesses on society is great. The studies outlined in this proposal will explore a novel nitric oxide/PKA/PKG-dependent mechanism by which ethanol impairs ciliary function. Establishing how ethanol both acutely stimulates and chronically desensitized ciliary motility in the airway epithelium will provide meaningful insight into the role alcohol ingestion plays in the pathogenesis of bronchitis, pneumonia and lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUEL OIL ASH AND HUMAN HEALTH Principal Investigator & Institution: Christiani, David C.; Professor; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001 Summary: Population-based epidemiologic studies of communities in the United States have revealed a consistent association between ambient particulate air pollution and increases in morbidity and mortality. The observed increases result from both respiratory and cardiovascular diseases for subjects over age 65. These ambient exposures are to levels of particulates many times lower than occupational exposures faced by workers in a variety of industries, including manufacturing, construction, transportation and electric-power generation. The objective of this proposal is to investigate the role of occupational exposure to particulates in the development of respiratory and cardiac responses in boilermakers with and without chronic bronchitis. We will employ a detailed continuous-exposure assessment to PM2.5 with repeated measures of biologic and physiologic markers of response. Specific hypotheses to be tested will include: (1) occupational exposure to fuel-oil ash particulates and associated metals induce airway inflammation as reflected in decreases in peak flow (PEFR) and FEV1; (2) particulate exposure and associated metals will result in acute changes in cardiovascular function, as reflected in changes in heart rate, heart-rate variability and blood pressure; (3) particulate metal exposure will result in increased serum fibrinogen levels, a known risk factor for cardiovascular disease; and (4) chronic bronchitis predisposes exposed workers to changes in cardiac function. The experimental approach will be an epidemiologic study employing a prospective, repeated measures design assessing several biologic parameters in relation to exposure. The expected results will clarify the relationship between exposure to oil-combustion ash metals and human cardiopulmonary responses in both normal and chronic bronchitic populations. Clarification of such exposure-response relationships will have important implications for preventive efforts aimed at reducing morbidity and mortality form exposure to respirable particulates and their associated metals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC, BIOLOGIC AND IMMUNOLOGIC DETERMINANTS OF ASTHMA Principal Investigator & Institution: Schechtman, Kenneth B.; Associate Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HOST DETERMINANTS OF ORGANIC DUST INDUCED AIRWAY DISEASE Principal Investigator & Institution: Schwartz, David A.; Professor of Medicine and Genetics; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 10-FEB-1999; Project End 31-DEC-2002 Summary: The goals of this proposal are to determine whether the airway response to inhaled endotoxin is a genetically based trait in humans and to assess to what extent the expression of this trait is influenced by gender. Occupational and environmental exposure to grain dust can cause asthma and bronchitis. Endotoxin appears to be one of
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the primary components of grain dust (and other organic dusts) that causes airway inflammation and airflow obstruction. Lipopolysaccharide (LPS) is a specific type of endotoxin found in the cell wall of gram-negative bacteria. In a murine model, we have confirmed that LPS resistance is determined by a single gene (Lps response gene), and we have localized this gene to a 220,000 base pair region on chromosome 4. In preliminary human studies, we have shown that most health, non-asthmatic, nonapoptotic, life-timer non-cigarette smoking volunteers develop airflow obstruction with challenged with increasing concentrations of inhaled LPS. However, approximately 10% of subjects developed marked airflow obstruction after inhaling trivial amounts of LPS and 15% of subjects appear to be hyporesponsive after inhaling over 40 micrograms of LPS. In addition, females demonstrate greater bronchial sensitivity to inhaled LPS than males. These results lead us to hypothesize that the airway response to inhaled LPS is a genetically determined complex trait in humans. Moreover, gender appears to substantially influence the airway response to inhaled LPS. We will use a familial cohort design to determine whether the airway response to inhaled endotoxin is a genetically based trait in humans, and to assess to what extent the expression of this trait is influence by gender. The study design is dependent on two interactive stages. In the first stage, we will screen a relatively large population of healthy, unrelated volunteers (n=200) with incremental doses of inhaled LPS. This will allow us to identify approximately 50 study subjects who will serve as "sensitive" or "hyporesponsive" probands. These sensitive and hyporesponsive probands will be used to identify families for the second stage of this investigation. In the second stage of the study, we will evaluate the airway response to incremental doses of inhaled LPS among 100 first degree relatives of up to 50 sensitive and hyporesponsive probands. Finds from this study will help us to determine why only a small portion of workers develop airway disease when exposed to organic dust. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF BIOCHEMICAL ABNORMALITIES IN PCD CILIA Principal Investigator & Institution: Ostrowski, Lawrence E.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: Primary ciliary dyskinesia (PCD) is an inherited disease which is characterized by various ultrastructural abnormalities in the cilia lining the respiratory tract. The defects in respiratory cilia are believed to result in impaired mucociliary clearance, and affected individuals suffer from recurrent respiratory infections, including rhinitis, sinusitis, bronchitis and pneumonia. In addition, many PCD patients also suffer from chronic otitis media, and males are frequently infertile. Currently, there is no curative treatment available for PCD, and the genetic basis of the disease is unknown. The long-term objectives of this proposal are to identify the genetic basis of PCD and to understand the pathogenesis of the disease. To achieve these goals, the following specific aims are proposed: 1: To identify protein(s) which are absent or altered in cilia isolated from cultured PCD cells. 2: To develop and characterize molecular and biochemical probes specific for the protein(s) which are altered in the cilia of PCD cells. 3: To determine if the gene coding for the protein(s) absent or altered in cilia from a PCD patient is mutated. Airway epithelial cells isolated from normal individuals and individuals with PCD will be cultured in vitro using techniques which allow the cells to differentiate into a well-ciliated epithelium. Cellular proteins will be radioactively labelled by the incorporation of labelled precursors and cilia will be
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isolated. The ciliary proteins will be compared using one- and two-dimensional polyacrylamide gel electrophoresis. Proteins which are altered or absent in the cilia from the PCD cells will be isolated and identified by mass-spectrometry. Antibodies and cDNA probes will be developed against the identified proteins. These probes will be used to determine if the gene coding for the protein is mutated, or if the protein appears altered in PCD cilia due to a mutation in another gene. These studies will identify defects in the cilia of PCD patients at the level of individual proteins. Ultimately, these studies will identify the mutation responsible for some cases of PCD, and will increase our understanding of how the mutation leads to disease. This information may lead to improvements in the diagnosis and therapy of this disease, including the possibility of gene therapy. Further studies of the role of these proteins in the assembly and function of cilia may also result in improved treatment for other air way diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IL-12 P80 MEDIATED AIRWAY INFLAMMATION Principal Investigator & Institution: Walter, Michael J.; Assistant Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Asthma is characterized by an inappropriate immune response manifested as enhanced accumulation of immune cells in the airway. In general, the immune response has been divided into innate and adaptive components, and recent evidence indicates the innate immune response generates inflammatory mediators that provide critical immunomodulatory signals to the adaptive immune system. In the particular context of the inflammatory response to inhaled materials, we have proposed the airway epithelial cells represent an ideal candidate to act as a primary sentinel site in innate immunity. This possibility was derived from observations that these cells express a network of immune-response genes that provide critical immunomodulatory and biochemical signals for immune cell influx, activation, and retention in the airway. The current proposal is based on several novel findings related to a member of the interleukin (IL)-12 family, called IL-12 p80 (p80). We identified the airway epithelial cell as a novel cellular source for p80 production following cytokine administration, infection with Sendai virus, and in subjects with asthma. Furthermore, Sendai viral infection of mice that lacked another IL-12 family member (IL-12 p35) overproduced p80 and displayed inappropriate inflammation characterized by enhanced accumulation of macrophages in the airway. Interestingly, in asthma subjects, but not normal or chronic bronchitis patients, we again found p80 overproduction that correlated with enhanced macrophage accumulation. Further studies demonstrated p80 functions as a macrophage chemoattractant and the IL-12 receptor beta 1 chain (IL-12Rbeta1) is necessary and sufficient to generate this p80dependent chemotactic response. Taken together, our results associate p80 overproduction with excessive viral and asthmatic inflammation, new functional consequences of p80 production in vivo, and p80-dependent immunomodulatory properties, such as macrophage chemotaxis, that are mediated through IL-12Rbeta1 signaling. Accordingly, the aims of this proposal are to define p80-dependent macrophage accumulation following SdV infection and characterize the proteins that mediate this response. In addition, we will define the structural components of IL12Rbeta1 that mediate p80-dependent chemotaxis. These studies will provide insight into the pathogenesis of inappropriate viral and asthmatic airway inflammation, and exploitation of this knowledge will provide the framework to develop selective regulators of p80 function in order to modulate this inflammation.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 2001; 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: INHALED PARTICLE CHARACTERISTICS AND EARLY LUNG EFFECTS Principal Investigator & Institution: Beckett, William S.; Professor; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2003 Summary: (Adapted from the Investigator's Abstract) Chronic obstructive pulmonary disease (COPD) is a disabling condition produced by chronic bronchitis (airway inflammation and mucus hypersecretion) and emphysema (loss of alveolar surface area). Epidemiologic studies of the workplace have consistently shown an excess of COPD associated with dusty work environments, yet only a few substances (coal, silica, cadmium) causing COPD in the workplace have been characterized based on chemical composition and respirable particle size. These findings suggest that the much broader range of workplace dusts may in certain conditions contribute to COPD based on characteristics other than chemical composition alone. Pulmonary inflammation plays a role in early events leading to COPD. Particles less than 10 micron aerodynamic diameter are considered to be able to penetrate the upper airways and reach the respiratory tract, and are thus designated as being in the respirable range. Ambient fine particles (<2.5um) consist of two fractions: ultrafines (0.01 to 0.1 um) and accumulation mode particles (0.1 to 1.0 um). Recent studies of ambient particulates indicate that ultrafine particles may be more harmful than other fine particles on an equal mass exposure basis. In animal models, ultrafine particles have a higher alveolar deposition fraction, translocate more easily from the airways to the interstitium, induce greater activation of macrophages and cytokine release, and cause greater impairment of macrophage clearance function.One reason for the greater toxicity of equal masses of these smaller particles is their much greater surface area. We hypothesize that the size of inhaled fine particles, in addition to their chemical and other physical characteristics, plays a critical role in determining occupational health effects. To test this we will study early lung and systemic inflammatory responses as well as cardiac effects in adults after carefully controlled inhalation exposure to ultrafine and accumulation mode zinc oxide, a particle we have previously characterized for the dose-response relationship of its short term pulmonary and systemic inflammatory effects. Studies will be conducted in the Environmental Exposure Facility of the Adult General Clinical Research Center. We will compare ultrafine to larger, accumulation mode particles (on an equal mass exposure basis) in their ability to produce symptoms, fever, markers of airway inflammation, antioxidants, systemic acute phase proteins, and alterations in the blood clotting cascade, cytokine release, heart rate, rhythm, and repolarization. We anticipate that the results will help to determine whether there are differential effects for equal mass exposures to fine particles of different size fractions in the pathogenesis of COPD Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INHIBITION OF MUCIN SECRETION IN MURINE MODEL OF ASTHMA Principal Investigator & Institution: Parikh, Indu; Biomarck Pharmaceuticals, Ltd 4364 S Alston Ave Durham, Nc 27713 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 28-FEB-2004 Summary: (provided by applicant): Hypersecretion of mucus into the respiratory airways is a major factor in several lung diseases, including chronic bronchitis, asthma, cystic fibrosis, and bronchiectasis. Despite the obvious medical importance, mechanisms that regulate production and secretion of airway mucus have not been elucidated fully, and, relatedly, there presently are no effective therapies to control excess mucus secretion in disease, and very few potential therapeutic targets. In previous NIH-funded research from the laboratories of the scientific consultants, a key molecule in the secretory pathway in human airway goblet cells was described. This molecule, MARCKS protein (Myristoylated Alanine-Rich C Kinase Substrate) plays a major role in regulating secretion of mucus in well-differentiated human airway epithelial cells in vitro. In the course of these studies, we developed a peptide to inhibit the function of MARCKS. The peptide corresponds to the N-terminal region of the MARCKS molecule. The peptide, named the MANS peptide, inhibits secretion of mucus by normal human bronchial epithelial (NHBE) cells in tissue culture in response to exogenous stimulation. A control peptide, consisting of the same N-terminal amino acids, but arranged in random order, has no effect. In the present application, we wish to determine if this peptide, instilled intratracheally into asthmatic mice that secrete excessive amounts of mucus can, similar to its effects in vitro, inhibit mucus secretion in vivo. If successful, these studies will be expanded in Phase II to include additional species, efficacy and toxicity studies, and research to optimize peptide solubility and stability; steps necessary for commercial development. The long-term goal is to develop a novel treatment that reduces mucus hypersecretion in the respiratory tract by directly blocking a step in the intracellular secretory pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INNATE BRONCHIOLITIS
IMMUNE
RESPONSES
IN
OBLITERATIVE
Principal Investigator & Institution: Palmer, Scott M.; Medicine; Duke University Durham, Nc 27706 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
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because of the incomplete understanding of the pathophysiology of BOS, and supported by several basic and clinical observations. We and others have recently demonstrated that significant polymorphisms exist in innate immune receptor genes, and that these differences significantly alter subsequent inflammatory and immune responses. In order to test our hypothesis, we will characterize polymorphisms in donor and recipient tolllike receptor-2 (TLR2), TLR4, and CD14 genes, and phenotypically characterize the airway physiological and biological response to endotoxin in a cohort of 120 lung transplant recipients. We will prospectively capture clinical information on the cohort and determine the predictive importance of innate genetic, physiological, or biological factors on the development or progression of BOS in a multivariate model. At the conclusion of the career development award, Dr. Palmer will have gained considerable expertise in study design, basic genetic analyses, transplant immunology, and statistical analyses. He will apply these skills to direct future investigations of patient oriented research problems in pulmonary medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACELLULAR ASSEMBLY OF THE CORONAVIRUS, IBV Principal Investigator & Institution: Machamer, Carolyn E.; Associate Professor; Cell Biology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): All enveloped viruses exploit the cellular secretory pathway for biosynthesis of their membrane proteins. The best studied enveloped viruses assemble by budding from the plasma membrane, where their membrane proteins accumulate. Assembly of enveloped viruses at intracellular membranes is less well understood, although these viruses must also accumulate their membrane proteins at the budding site. Intracellular assembly of the avian coronavirus infectious bronchitis virus (IBV) in the cis Golgi network will be studied. Coronaviruses are ubiquitous in vertebrates, and in humans cause mild respiratory disease (responsible for about 20 percent of common colds). Coronaviruses are conveniently studied in cell culture systems, and are thus an ideal model for intracellular virus assembly. Understanding the intracellular assembly of enveloped viruses is important because several virus families that cause significant human disease assembly at intracellular membranes. These include Bun yaviridae and Flaviviridae. The long term goals of the proposed experiments are to elucidate the mechanism and advantages of intracellular assembly of enveloped viruses, and to identify unique strategies to interfere with assembly and infection by this subset of viruses. Specifically, the experiments are designed to test the following hypotheses: (1) the IBV RNA 3 proteins (3a, 3b, and E) play important roles in virus assembly and infection; (2) the IBV E protein has an additional function in infected cells to slow membrane traffic, allowing S to accumulate at the budding site and possibly preventing virus antigen presentation to the immune system; and (3) distinct envelope lipids (derived from the cis Golgi network) provide an advantage for the virus during subsequent rounds of infection by promoting fusion with susceptible cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM BASED INHIBITORS OF SERINE PROTEINASES Principal Investigator & Institution: Groutas, William C.; Distinguished Professor; Chemistry; Wichita State University Wichita, Ks 67208 Timing: Fiscal Year 2001; Project Start 10-DEC-1997; Project End 30-NOV-2001
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Summary: An array of inflammatory diseases such as pulmonary emphysema, chronic bronchitis, cystic fibrosis, psoriasis, rheumatoid arthritis and others, are characterized by an influx of neutrophils, and the presence of mediators of inflammation and cytokines that serve as neutrophil chemoattractants. The recruitment and degranulation of neutrophils in inflammatory states results in the production of reactive oxygen species and the extracellular release of the serine proteinases elastase, cathepsin G and proteinase 3. Poor regulation of the activity of these enzymes because of depressed levels of their physiological protein inhibitors leads to the degradation of the major components of the extracellular matrix and, ultimately the onset of disease. The use of innovative strategies that seek to counteract the damaging effects of the renegade enzymes be reestablishing a proteinase/antiproteinase inhibitor balance constitutes the long-term objective of the proposed research. The use of a potentially universal heterocyclic scaffold in the design of mechanism-based inhibitors that endows these inhibitors with unique mechanistic features and optimal biochemical properties is proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF OXIDANT-INDUCED CHRONIC BRONCHITIS Principal Investigator & Institution: Forteza, Rosanna M.; Assistant Professor; Medicine; University of Miami Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Mucus hypersecretion, goblet celt hyperplasia and metaplasia as well as submucosal gland hypertrophy are pathophysiological and histological hallmarks of chronic bronchitis. The activation of epidermal growth factor (EGF) signaling is believed to be responsible for many of these morphological changes of the airway epithelium. Cigarette smoke, the major cause of chronic bronchitis in human subjects, has also been demonstrated to induce mucin secretion and mucous cell hyperplasia, at least in part, via oxidative stress and EGF signaling. EGF is expressed in the airways, stimulates the EGF receptor (EGFR) and, as shown by us, is made from proEGF through cleavage by tissue kaltikreJn (TK). We have also shown that TK is secreted by submucosal glands together with hyaluronan, which inhibits the activity of TK. Hyaluronan also immobilizes bronchial TK at the epithelial surface, creating a pool of readily available, yet inactive TK at the airway surface. Reactive oxygen species (ROS) can cleave hyaturonan, thereby releasing activateded TK. In chronic bronchitis, ROS and active TK are elevated in the airway compared to normal subjects, possibly due to continued degradation of hyaluronan by ROS. We hypothesize that the increased availability of active TK in these conditions is a critical link between oxidative stress and EGF-mediated airway mucous cell hyperplasia. This proposal will test the hypothesis that ROS-mediated goblet cell metaplasia and submucosai gland celt hyperplasia occurs through a multi-step cascade beginning with hyaturonan degradation (initiation step) that results in sustained release of activated TK (priming step) and thereby increased availability of mature EGF (activation step) that in turn activates EGFR (signaling step). The specific aims are: 1) to confirm and extend our preliminary in vitro observations that ROS degrade epithelialbound hyaluronan and thereby release active TK that in turn cleaves pro-EGF to activate EGFR (proof of concept in culture); 2) to evaluate hyaluronan degradation, TK activation and pro-EGF processing in airways obtained from patients with chronic bronchitis (proof of concept in human disease); and 3) to examine whether TK-mediated pro-EGF cleavage regulates submucosal gland cell proliferation (relevance of concept). The proposed experiments will thus examine a new
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link between oxidative stress and chronic bronchitis and may identify new approaches to prevent or even reverse such changes in the airway mucosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF REMODELING IN CHRONIC AIRWAY INFLAMMATION Principal Investigator & Institution: Caughey, George H.; Professor; Cardiovascular Research Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-1979; Project End 30-JUN-2004 Summary: This application requests funds to continue multi-disciplinary studies of cellular and molecular mechanisms of airway remodeling of chronic inflammation. Drs. Basbaum, Caughey, and McDonald have collaborated closely in this Program Project Grant for may years and now, with the addition of Dr. Killeen, and experienced immunologist, will direct their efforts to the cellular and molecular pathophysiology of chronic inflammation of the airways. The investigators will focus on the mechanisms and consequences of the influx of inflammatory cells and changes in the epithelium, vasculature, and connective tissue matrix that result in airway remodeling. Using stateof-the-art molecular, cellular, morphological, immunological, and transgenic approaches, the Program Project team will approach the problem in four ways. Project 1, led by Dr. Basbaum, will explore the roles of recruited leukocytes in regulating epithelial hyperplasia, metaplasia, and mucin gene expression. The project, led by Dr. Caughey, will investigate roles of proteases from mast cells and other airway cells in regulating microvascular, epithelial, and matrix remodeling. The project led by Dr. Killeen, will examine roles of lymphocytes and novel TNF-family receptors in the remodeling of the airway microvasculature and epithelium. The project led by Dr. McDonald, will examine the mechanisms and consequences of microvascular remodeling in chronic airway inflammation and will explore the use of angiostatic drugs to reverse the remodeling Mycoplasma pulmonis infection in normal and genetically altered mice will be used in many of the studies is a model for studying chronic airway inflammation. The Program Project team has a long tradition of collaborative research and the use of multi-disciplinary strategies for studying airway inflammation. Collectively, they have a powerful armory of skills in cellular and molecular biology, enzymology, microscopy, immunology, and organ physiology to solve the mysteries of airway remodeling in chronic disease. Understanding the causes of remodeling will suggest novel strategies to prevent or reverse the long lasting changes in the airway wall typical of asthma bronchitis, cystic fibrosis, and other chronic inflammatory diseases, which affect a growing share of the population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MESENCHYMAL STEM CELL HOMING TO THE LUNG IN EMPHYSEMA Principal Investigator & Institution: Welsh, David A.; Medicine; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Chronic Obstructive Pulmonary Disease (Chronic Bronchitis & Emphysema) is a leading cause of morbidity & mortality in the United States. Emphysema is histologically defined as the destruction of alveolar walls without significant fibrosis. Regeneration of alveoli in the emphysematous lung should improve
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pulmonary function and lessen the burden of this common disease. Marrow Stromal Cells (MSCs) are pluripotent cells that can be harvested from adult bone marrow and can potentially be used in tissue repair. The currently achievable, low levels of engraftment in the lung are unlikely to result in clinically significant improvements in pulmonary function. Therefore this proposal focuses on enhancing recruitment and engraftment of MSCs to the lung. This proposal will test the hypothesis that population of "stem sites" in the alveolar wall with bone marrow-derived stromal cells will allow "neo-alveolarization" to occur in the emphysematous lung with restoration of alveolar morphology and function. The 1st specific aim of the project will confirm the hypothesis that homing of MSCs to the lung is increased in the elastase-induced rat model of emphysema. Administration techniques will be optimized. These interventions will be assessed by transplanting MSCs harvested from male rats into female rats previously treated with intratracheal elastase and quantitating engraftment by chimerism of the X& Y-chromosomes. Engraftment will be confirmed by fluorescent microscopy (of EGFPtransgenic MSCs), immunohistochemistry & FACS analysis. The 2nd specific aim investigates the expression of chemokine receptors on MSCs and chemokine ligands by the injured lung. Specific aim 3 will expand on this by exploring the effects of chemokines on MSC migration in vitro and lung recruitment in vivo by over expression of ligand through tetracycline-regulated gene therapy techniques. Finally, in Specific Aim 4 the benefits of enhancing recruitment to the lung will be defined by assessing the morphologic and functional impact of MSC transplantation. These studies will expand our understanding of the biology of MSCs & methods to improve recruitment to the lung, hopefully leading to novel therapies for emphysema. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: KNOCKOUT
METALLOELASTASE
INDUCTION
FOLLOWING
INTEGRIN
Principal Investigator & Institution: Morris, David G.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 08-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant?s abstract) Dr. David Morris is a pulmonary and critical care physician with a strong commitment to an academic career as an independent investigator in respiratory cellular and molecular biology. His particular interest is lung remodeling. Through work in the Lung Biology Center at UCSF/SFGH he has identified a novel animal model of bronchitis and emphysema resulting from inactivation of an epithelial integrin (alpha2- beta6). He is proposing a program of advanced research training consisting of independent experimental studies mentored by an expert in integrin biology (Dr. Dean Sheppard); a research advisory committee including experts on matrix metalloproteinases (Dr. Zena Werb), protease biology (Dr. Caughey), and pulmonary immunology (Dr. Erle); and a formal didactic program including courses in biochemistry, cell biology, and immunology. His research program will address the hypothesis that the integrin alpha2-beta6 on the surface of respiratory epithelial cells modulates alveolar macrophage expression of Macrophage Metalloelastase (MME, MMP-12) thereby regulating airway inflammation, and matrix degradation. He will address this hypothesis through three specific aims. First, he will determine which regions of the beta6 integrin subunit are critical to prevent persistent MMP-12 (MME) overexpression by alveolar macrophages and avert the development of emphysema in beta6 -/- mice using novel transgenic lines. Second, he will determine the role of MMP-12 (MME) upregulation in the recruitment and activation of macrophages and lymphocytes in beta6 -/- mice using double knockout mice. Finally, he will
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determine the role of Transforming Growth Factor Beta1, and of alpha2-beta6 mediated activation of latent TGFbeta1 in the regulation of airway inflammation and MMP-12 (MME) expression in vivo using both adenovector gene transfer and transgenic approaches. This work promises to yield important insights into the fundamental biology underlying both chronic airway inflammation and emphysema. Dr. Morris will complete this work in the Lung Biology Center (LBC), internationally recognized research center with an outstanding record of training independent academic pulmonary scientists. The Department of Medicine and LBC are fully committed to Dr. Morris? career development and to making all necessary resources available to facilitate successful completion of this work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MINIMIZING ANTIBIOTIC RESISTANCE IN COLORADO (MARC) Principal Investigator & Institution: Gonzales, Ralph; Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: A broad-based coalition of stakeholders has collaborated to reduce excess antibiotic use in Colorado by developing and disseminating clinical practice guidelines and practice profiles to 2600 primary care physicians throughout the state. Whether, how much and what type of public and patient education to employ on large-scale efforts to decrease unnecessary antibiotic use is not known. The Minimizing Antibiotic Resistance in Colorado (MARC) Project is designed to evaluate the independent and combined marginal impact of two common mechanisms of public and patient education in clinician prescribing behavior: 1) household and office-based materials, and 2) mass media (television, radio, newsprint, web site). The following specific aims will examine the processes and outcomes of care related to each intervention strategy. Results from this project will inform state and federal efforts to improve ambulatory antibiotic prescribing practices. Specific Aim IA: Develop and implement community educational interventions using (1) household and office-based materials, and (2) mass media. Specific Aim IB: Measure and assess changes in antibiotic prescription rates for pharyngitis in children, and bronchitis in adults, using commercial MCO and Medicaid administrative data from physician practices. Specific Aim IIA: Conduct household surveys in and outside the intervention communities to measure the impact of each education strategy on public knowledge, attitudes, behavior and self- efficacy. Specific Aim IIB: Conduct a clinician judgment analysis to measure the impact of each education strategy on clinician decision making and empowerment relating to episodes of care for pharyngitis and bronchitis. Specific Aim IIIA: Conduct a survey of patients and parents to measure the impact of decreased antibiotic use on duration of illness and satisfaction with care, for children with pharyngitis and adults with bronchitis. Specific Aim IIIB: Using active surveillance data from the Colorado Department of Public Health and Environment (CDPHE), compare the incidence of invasive penicillin-resistant S. pneumoniae infections in and outside the intervention communities. Specific Aim IIIC: Conduct a net-cost analysis of the different levels of community education. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR AND FUNCTIONAL STUDIES OF H INFLUENZAE PILI Principal Investigator & Institution: Gilsdorf, Janet R.; Professor of Pediatrics; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274
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Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): Haemophilus influenzae (Hi) are significant cause of respiratory tract infections, including sinusitis, otitis media, bronchitis, and pneumonia. The first step in the development of Hi infections is colonization of nasopharyngeal tissues, which depends on the ability of Hi to adhere to nasopharyngeal cells. To this end, Hi have evolved pili that bind to gangliosidecontaining receptors on epithelial cells and human red cells. Hi pili are complicated structures composed of at least three proteins, including HifA (the major pilus subunit), HifD (whose function is poorly defined), and HifE which contains the actual epithelial cell adhesin. The long-term goal of this project is to identify strategies to interfere with Hi adherence and, thus, prevent Hi infections. This goal will be met through understanding the underlying mechanisms by which the HifE adhesin of Hi mediates adherence to human tissue. Specific Aim I is designed to identify the receptor binding domain(s) of HifE through three approaches: 1. To analyze the amino acid sequences of HifE from Hi respiratory and invasive strains for conserved regions; 2. To identify epitopes defined by monoclonal antibodies that interfere with pilus mediated Hi binding to erythrocytes and epithelial cells; 3. To construct mutations in candidate receptor binding domain(s) by alanine-replacement and to test the function of the mutants in adherence assays. Specific Aim II is designed to compare the receptor binding domain(s) of Hi strains (biotype IV and biogroup aegyptius strains) that occupy unique niches within humans and may possess distinctive receptor binding domains. Specific Aim III is designed to identify tissue specificity of the receptor binding domain(s), by testing in competitive inhibition assays the binding of receptor binding domain mutants to a variety of human epithelial cells and by determining the role of the pilus stalk in binding specificity. Specific Aim IV is designed to identify the immunogenic potential of the receptor binding domain(s). Rabbit antisera will be raised to the domains and binding of the antibodies to HifE assessed by whole cell dot blot assays, Western blot assays, and immunoelectron microscopy. The receptor binding domain antibodies will be tested for their ability to interfere with the adherence of piliated Hi to human erythrocytes and respiratory cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR PATHOLOGY OF CHRONIC LUNG DISEASE Principal Investigator & Institution: Gerard, Craig J.; Professor and Director; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 15-JUL-1994; Project End 31-MAY-2003 Summary: The polymorphonuclear neutrophil (PMN) serves a critical role in the lung as a principal component in acute host defense. However, a number of lung diseases, including chronic bronchitis/ chronic obstructive pulmonary disease, acute respiratory distress syndrome, asthma and cystic fibrosis display a pathologic inflammatory component where neutrophils are destructive to lung tissue. Our principal hypothesis, that the C5a anaphylatoxin and the chemokine IL-8 represent the dominant chemoattractants mediating neutrophil trafficking to the lung, has been supported by our initial studies with mice genetically altered to be deficient in chemoattractant receptors. A non-redundant role for C5a and its receptor was identified in two models of lung inflammation. C5a receptor (C5aR) deficient mice are completely protected from immune complex-mediated lung injury, while they are rendered incapable of clearing intrapulmonary pseudomonas aeruginosa despite a vigorous inflammatory infiltrate. The present competing renewal grant seeks to continue these studies, which will
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Bronchitis
identify the specific roles played by the C5a and IL-8 ligand receptor pairs using a molecular genetic approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUC4 MUCIN AND AIRWAY EPITHELIAL REGENERATION IN COPD Principal Investigator & Institution: Voynow, Judith A.; Assistant Prof. of Pediatrics; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): In chronic obstructive pulmonary diseases such as chronic bronchitis, and in cystic fibrosis, the airway epithelium is constantly exposed to neutrophil elastase (NE), an inflammatory protease. The cellular response to NE dictates the balance between epithelial injury and repair. A critical factor in this balance is the activation of the epidermal growth factor receptor (EGFR), a member of the ErbB receptor tyrosine kinase family. Activation of EGFR requires homo- or heterodimerization of the receptor. A major EGFR heterodimerization partner in airway epithelial cells is ErbB2. To date, the only ligand known to activate ErbB2 is MUC4. MUC4 is a major membrane-tethered, respiratory tract mucin with epidermal growth factor (EGF)-like domains. We have made four key observations supporting a critical role for MUC4 in activating the airway epithelial response to NE: (1) NE acts on airway epithelial cells to enhance MUC4 mRNA stability and increase MUC4 protein levels. (2) NE induces tyrosine phosphorylation of EGFR. (3) NE stimulates proliferation of normal human bronchial epithelial cells in serum-free and EGF-free media. 4. MUC4, ErbB2 and EGFR colocalize in injured superficial airway epithelial cells in vivo. These observations support the hypotheses that NE triggers a molecular cascade of events in airway epithelial cells by inducing the production of MUC4, a key regulatory molecule in the cascade, activating ErbB2, and thereby promoting the heterodimerization/activation of EGFR. EGFR activation is a critical prerequisite for epithelial proliferation. The Specific Aims to be tested in this proposal are: (1) To determine whether NE induces MUC4activation of the ErbB2/EGFR receptor tyrosine kinase cascade, resulting in epithelial cell proliferation. (2) To identify the RNA stability domains and RNA-binding proteins regulating NE-induced expression of MUC4, a key molecule in this signaling cascade. (3) To determine the relevance of these signaling pathways in mediating epithelial proliferation in vivo in chronic bronchitis and cystic fibrosis. Our ultimate goal is to use information from this project to identify new biologic targets for rational therapies to induce normal airway epithelial proliferation and differentiation following injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MURINE MODELS OF OCCUPATIONAL COPD Principal Investigator & Institution: Leikauf, George.; Professor; Environmental Health; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Chronic obstructive pulmonary disease (COPD) is marked physiologically by airflow limitations and pathologically by mucosal injury and inappropriate repair in the airway (bronchitis) and parenchyema (emphysema). COPD is currently the fourth leading cause of death in the United States and has long been associated with certain occupations. These include mining, chemical manufacturing, farming, food preparation, and farming. A common feature of COPD, airway mucus hypersecretion is due to excessive production of mucins. These proteins provide the characteristic viscosity,
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adhesiveness, and elasticity to the mucus lining the airways. To date, nine human mucin genes have been identified and partially characterized in lung disease. This study seeks to use a potent aldehyde, acrolein, to induce mucus hypersecretion in a laboratory species. This aldehyde is a member of a chemical class, the low molecular weight aldehydes, that have excessive use in industry and can result in wide industral exposures. Acrolein is also produce by a number of combustion processes and can be found in diesel, wood, and cigarette smoke in high concentrations. The overall hypothesis of this study is that occupational aldehyde exposures can induce mucus hypersecretion by direct and indirect inflammatory mechanisms. Specific aims include: (1) To develop a mouse model for the study of acrolein-induced COPD, (2) To further investigate the role of macrophage/monocyte or neutrophil infiltration in mucus hypersecretion, and (3) To begin to investigate the genetic determinants of individual susceptibility. These aims will be completed using novel research approaches (including normal, transgenic, and knockout mice with deficient or enhanced leukocyte migratory capacities). Genetic analyses will include strain distribution pattern, mode of inheritance, recombinant inbred, and quantitative trai locus analysis. The wellcharacterized mouse model generated by this proposal will be useful in the further understanding of the relationship between occupational exposures, genetic markers, inflammatory responses, and COPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINIC RECEPTORS IN NONNEURONAL CELLS AS TARGETS FOR NICTOINE TOXICITY Principal Investigator & Institution: Conti-Fine, Bianca M.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: Bronco epithelial cells, endothelial cells and esophagus keratinocytes express nicotinic acetylcholine receptors of neuronal type (nAChR) sensitive to nicotine (Nic): the overall goal of the proposed studies is to identify new mechanisms of Nic toxicity resulting from a direct effect on those nAChRs. Block of the nAChR in bronchial epithelial and endothelial cells causes cell paralysis and cell-cell detachment. Long term exposure to Nic causes nAChR desensitization, and will likely result in cell-cell detachment, leading to bronchitis and esophagitis, atherosclerotic lesions, and facilitated entrance of carcinogenic compounds. Acute exposure of bronchial epithelial cells to Nic causes apoptosis, that might be an additional mechanism of Nic toxicity. The proposed studies will have three major (1 to 3), and three minor (4-6) specific aims: 1) to investigate the structural and functional properties of nAChRs expressed by bronchial epithelial cells, endothelial cells and esophagus keratinocytes; to extend these studies to lung alveolar epithelial cells; by patch clamp and binding studies using ligands specific for different nAChR subtypes; by immunohistochemistry, using antibodies and protein probes specific for different nAChR subtypes; by PCR using subunit specific primers, followed by cloning and sequencing of the products; by in situ hybridization using subunit specific probes. 2) to demonstrate in these cells the presence of the enzymes that metabolize ACh; by immunohistochemical and to demonstrate in these cells the presence of the enzymes that metabolize ACh; by immunohistochemical and biochemical assays of the enzymes choline acetyltransferase and acetylcholinesterase. 3) to investigate the cellular functions modulated by Nic and ACh binding , and the effects of acute and chronic Nic exposure in vitro, using functional assays of cell adhesion, motility, and proliferation, and by measuring the rate of cell death and apoptosis after exposure to Nic. 4) to investigate the possibility that the nAChRs expressed by bronchial
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Bronchitis
epithelial cells are a port of entry for rabies virus, explained rabies cases that result from airborne exposure. 5) to investigate the characteristics of the endothelia nAChRs expressed in patients with Buerger's disease, a vasculitis of the limb blood vessels caused or triggered by tobacco usage. 6) to do pilot investigations to test whether nAChRs are expressed at other non-neuronal locations involved in tobacco toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NKP608 CAPSULES IN ADULT PATIENTS WITH CHRONIC BRONCHITIS Principal Investigator & Institution: Mcfadden, E R.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Specific Aims and Hypothesis: The purpose of this study is to identify if the administration of NKP 608 decreases sputum production and improves the clinical symptoms of chronic bronchitis. The primary experimental objective is to compare the effects of placebo and four daily doses (0.1mg, 1mg, 5mg, 20mg) of NKP 608 upon the amount of sputum that can be induced by hypertonic saline. The secondary experimental objectives are to evaluate the effect of NKP 608 on: health related quality of life and clinical signs and symptoms of chronic bronchitis, the safety and tolerability compared to placebo, and population pharmacokinetics in a sample trial population. This study will employ a multiple-center, randomized, double-blind, placebo-controlled, parallel group design. Patients will make 6 visits to the investigation site. Subjects must have been taking all allowed concomitant medications without change for at least 2 weeks prior to screening. Subjects with chronic bronchitis that have a forced expiratory flow rate (FEV1) is greater than or equal to 35% of predicted and whom have no other unstable disease will be screened for inclusion in the study. Approximately 10-20 ml of blood will be drawn at each visit. Each subject will also undergo a physical exam. The ECG will be repeated on Visit 4 and Visit 6. Lung function will be evaluated by spirometry. Bronchodilator medications will be withheld for a minimum of 6 hrs. prior to testing. Daily diaries will be completed. The study has been closed by the sponsor. 15 subjects were screened, 10 enrolled and 8 completed the study at the site. Data is being compiled by the sponsor and results are not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL PA1-INHIBITORS OF NEUTROPHIL PROTEINASES Principal Investigator & Institution: Day, Duane E.; Molecular Innovations, Inc. 21315 Hilltop St Southfield, Mi 48304 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Neutrophil elastase and cathepsin G are serine proteases stored within the primary granules of neutrophils. The activation and degranulation of neutrophils at inflammatory sites result in the release of these proteases where they encounter inhibitors that regulate their activity in certain inflammatory conditions. These proteases have been implicated in the pathogenesis of a variety of diseases. One example of an inflammatory disease associated with neutrophil recruitment is Chronic Obstructive Pulmonary Disease (COPD). COPD is a slowly progressive and incurable disease of the airways, characterized by a gradual loss of lung function. An estimated 20.9 million Americans are currently affected by COPD; of which 18.3 million suffer from chronic bronchitis and 2.7 million suffer from emphysema. Our Phase I study involved the development of two rationally designed mutants of
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Plasminogen Activator Inhibitor One (PAI-1). The normal targets for PAl-1 are the plasminogen activators tPA and uPA. The gene for PAl-1 has been altered to produce mutants with altered protease specificity. These two new mutant inhibitors now target neutrophil elastase and cathepsin G. Due to the unique properties of PAl-1, these mutants actually exhibit properties superior to the natural inhibitors Alpha One Proteinase Inhibitor and Antichymotrypsin. Specifically, these mutants both inactivate and facilitate the cellular endocytosis and degradation of the neutrophil proteinases in the presence of polyanionic surfaces such as heparin and DNA, which sequester these very basic enzymes. The DNA that codes for these mutants has been cloned into a E. coli bacterial construct for expression at very high levels, and a patent pending method for the purification of PAl-1 will be scaled up in our Phase II study. The Phase II proposal extends and expands our studies to include: improving the properties of the mutants for therapeutic use, further characterization of the performance of the mutants compared with commercially available and endogenous inhibitors in a number of animal models, development of sensitive and specific immunoassays for neutrophil elastase and cathepsin G and, a study to examine the large scale production of the PAl-1 mutants using a rapid patent pending purification process. Destructive lung diseases are a major cause of morbidity in the U.S. We believe that these mutants can be developed into therapeutic agents for the treatment of a variety of inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: O3/ENDOTOXIN COEXPOSURE EFFECT ON AIRWAY EPITHELIUM Principal Investigator & Institution: Harkema, Jack R.; Professor; Pathology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2001 Summary: (Adapted from the Investigator's Abstract): The goal of this project is to understand how inflammation induced by the inhalation of bacterial endotoxin affects the response of the airway epithelium to ozone, the principal oxidant air pollutant in photochemical smog. Each toxicant alone causes airway inflammation that is followed by mucous cell metaplasia characterized by proliferation of mucus-secreting cells in regions of the airway that normally contain no or few secretory cells. Mucous cell metaplasia is a common pathologic feature of airway diseases, such as chronic bronchitis, cystic fibrosis, and asthma. The consequences of co-exposure to these two airborne pollutants have not been fully explored. These studies will focus on the effects of co-exposure on the pathogenesis of: 1) the initial epithelial cell injury and inflammation, and 2) the subsequent induction of mucous cell metaplasia associated with mucin synthesis and secretion. Experiments will extend preliminary findings indicating that co-exposure of rats to endotoxin and ozone will induce greater premetaplastic lesions (airway inflammation and epithelial cell loss) than exposure to either toxicant alone. Studies will determine if the magnitude of the premetaplastic epithelial lesions is dependent on the initial inflammatory cell response. Studies will also focus on the pathogenesis and severity of the mucous cell metaplasia caused by coexposure to ozone and endotoxin by determination of nasal and bronchial airways epithelial differentiation, increased mucin mRNA, hypersecretion of mucins. The role of ozone/endotoxin-induced inflammatory cell response in the overproduction of airway mucus will be examined. A combination of morphometric, histochemical, immunochemical, and molecular techniques will be used to identify temporal alterations in epithelial cell populations, intraepithelial mucosubstances, mucin gene expression, and mucin secretion in nasal and pulmonary airways. The results from these studies will reveal interactive effects of co-exposure on the mucous apparatus of the
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nasal and pulmonary airway epithelium, and the role of neutrophils in the amplification of airway alterations due to co-exposure to ozone and endotoxin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL LY333013 AND METHOTREXATE DRUG INTERACTIONS STUDY Principal Investigator & Institution: Branch, Robert A.; Professor/Director; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: This is a two-part study (A&B) designed to evaluate the safety and tolerability of commitant LY333013 and methotrexate administration in rheumatoid arthritis patients. Each part of this multicenter study will be conducted independently and will consist of a single blind, placebo controlled, randomized two period crossover. LY333013 is a prodrug of LY315920 which is a potent inhibitor of human non-pancreatic secretory phospholipase A2 (sPLA2). LY333013 is being developed for oral administration in patients with chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, asthma and chronic bronchitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS OF VIRAL PROLIFERATIVE BRONCHIOLITIS Principal Investigator & Institution: London, Lucille; Associate Professor; Microbiology and Immunology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): Bronchiolitis obliterans with organizing pneumonia (BOOP) is a term for a long observed, but unclassified pattern of acute lung injury. In humans, BOOP is characterized by fibrosis of small airways with fibrous extension into the alveolar spaces with preservation of alveolar ducts and walls. It is frequently associated with a peribronchiolar organizing pneumonia. The lesions may also be accompanied by lipid-laden foamy alveolar macrophages trapped in the air spaces by the fibrosis and by a T cell rich lymphocytic interstitial infiltrate in the regions of the lung directly affected by the lesion. Also, necrosis and sloughing of epithelial cells has been observed and is thought to result in the partial alveolar collapse seen in human BOOP. While BOOP can be associated with documented viral and bacterial infections, many cases are not associated with known causes and are thus classified as idiopathic. Little is known concerning the pathogenesis and treatment of BOOP since no animal models were available for this disorder. The investigators are the first to establish an experimental animal model for this disease. In this model, CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions which closely resemble the histopathological picture of human BOOP. In addition, the development of BOOP lesions in CBA/J mice is virus strain specific. The central hypothesis of this proposal is that "Disruption of the epithelial basement membrane determines the susceptibility to fibrosis". The investigators propose to characterize the host and/or viral factors (both immune and non-immune cellular populations) that result in initiation of damage to the basement membrane and relate these finding to the development of fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEDIATRIC EBM-GETTING EVIDENCE USED AT THE POINT OF CARE Principal Investigator & Institution: Davis, Robert L.; Associate Professor; Pediatrics; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: The applicant plans to study the provision of evidence at the point of pediatric care, in order to increase the application of evidence- based medicine, change physician behavior, and expedite the translation of research into clinical practice. There will be two main questions. First, that use of an evidence-based decision support system at the point of care will improve antibiotic use in specific index pediatric outpatient diseases, and will (i) reduce frequency and duration of antibiotic therapy for otitis media, (ii) reduce duration of therapy for acute sinusitis, (iii) reduce use of bronchodialators in outpatient treatment of bronchiolitis, and (iv) increase use of intranasal steroids for allergic rhinitis. Second, that individualized physician feedback will provide additional benefit, when used in conjunction with the support system. This study will be carried out through a series of randomized controlled trials, implemented at three sites, including academic pediatric and family medicine health care centers, rural and suburban pediatric clinics, and a regional pediatric emergency department. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOKINETICS OF GREPAFLOXACIN & CIPROFLOXACIN IN LUNG Principal Investigator & Institution: Bascom, Rebecca; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001 Summary: The purpose of this study is to determine the concentration of the antibiotic Grepafloxacin (Raxar) or Ciprofloxacin (Cipro) in the lung after taking a single dose. Both drugs are used for treating lung infections such as pneumonia and acute exacerbations of chronic bronchitis caused by bacteria that are resistant to many antibiotics. The greater the amount of antibiotic that is deposited at the site of the infection, the faster the bacteria is eliminated and the course of treatment is shorter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PORTABLE CONTINUOUS OXYGEN SYSTEM Principal Investigator & Institution: Appel, W Scot.; Sequal Technologies, Inc. 11436 Sorrento Valley Rd San Diego, Ca 92121 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a serious public health problem that is responsible for more than 500,000 hospitalizations, 100,000 deaths, and $15 billion in direct costs of medical care in the U.S. each year. In addition, millions of Americans are disabled by lung disease. It is estimated that more than 16 million people have undiagnosed COPD. Patients, whom have developed emphysema or obstructive bronchitis or who are afflicted with long-standing, low, blood-oxygen levels (chronic hypoxemia), typically require supplemental oxygen. Oxygen concentrators--electrically powered mechanical devices that extract oxygen from air by a process known as Pressure Swing Adsorption (PSA)--are the most prevalent devices used to provide supplemental oxygen (0.5 - 3.0 liters per minute). When low-flow supplemental oxygen is prescribed for the treatment of COPD or chronic hypoxemia, a patient is provided with a stationary oxygen concentrator for use in their home, plus several small tanks of gaseous oxygen and accessories (an oxygen conserving device & pressure regulator) for ambulation or excursions outside their home, including airline travel. SeQual Technologies has developed an advanced PSA gas separation system for the generation of oxygen for medical applications. This proprietary system incorporates a rapid vacuum-pressure-swing adsorption process that enables SeQual to provide a PSA unit with both the highest recovery (the ratio of output oxygen molecules to input oxygen molecules) and the greatest productivity (the oxygen output flow rate per unit volume of the system) of any medical oxygen concentrator. The Company's proprietary PSA devices--in combination with state-ofthe-art, high efficiency, lightweight motors and compressors--have enabled SeQual to produce a unique, portable, battery-operated, oxygen concentrator system. SeQual's continued efforts remain in the improvement of the efficiency, productivity and recovery of oxygen molecules during the PSA process to effectively miniaturize the oxygen generation device that will lead to a very small scale portable oxygen concentrator that can deliver continuous oxygen to a patient at all times. The focus of this research is on novel monolithic structured adsorbents. The study proposes to characterize the surface area of the structures, study the effectiveness of the unique pressure swing adsorption cycles and parameters and design a very small system for the concentration of oxygen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSPORT
PROTEASE
REGULATION
OF
AIRWAY
CELL
49
SODIUM
Principal Investigator & Institution: Bridges, Robert J.; Professor; Cell Biology and Physiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: (provided by applicant): Electrogenic transepithelial Na+ transport is mediated by an apical membrane, amiloride sensitive Na+ channel (ENaC) and plays an important role in the physiology of a number of organs including the kidney, colon, sa1ivary, and sweat glands as well as the lungs. Sodium transport in the lungs has an important impact on mucociliary clearance, which is impaired in a number respiratory diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma and acute and chronic bronchitis. Pharmacological modulation of Na+ transport is expected to improve mucociliary clearance in these diseases. In this application, we present results that demonstrate 70 percent of Na+ transport, in primary cultures of human bronchial epithelial cells (HBE), is regulated by a novel extracellular protease-mediated mechanism. We will show that HBE cells express an endogenous protease, prostasin, that we hypothesize is the ENaC channel activating protease (CAP). In addition, we will show that an endogenous protease inhibitor, bikunin, inhibits Na+ transport and this inhibitory effect can be reversed upon washout of the inhibitor or by the addition of exogenous protease. We are convinced this protease/protease inhibitor mediated mechanism represents a paradigm shift in how we view the regulation of ENaC with important basic science and therapeutic implications. Our specific aims are designed to test several hypothesis predicated on a model we have proposed to explain the mechanism of protease/protease inhibitor mediated regulation of ENaC in the airways. The hypotheses we will test include: (i) prostasin is the HBE CAP, (ii) that prostasin directly binds to ENaC and proteolysis one or more of the subunits to cause ENaC activation, (iii) that inactive ENaC is inserted into the apical membrane where it is activated by prostasin and has a short half-life as an active channel before being retrieved and degraded, (iv) that bikunin inhibits prostasin via its Kunitz' domains and (v) that the binding site on ENaC for prostasin is at the Kunitz-like domain in the second cysteine rich domain of the channel. We will use short circuit current measurements, fluctuation analysis, site directed mutagenesis protein biochemical and high resolution field emission scanning electron microscopy methods to test our hypotheses. The successful completion of our proposed studies is certain to provide new an important insight about how ENaC is regulated by this novel extracellular mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOLYTIC ENZYMES AND INHIBITORS IN LUNG DISEASE Principal Investigator & Institution: Travis, James; Professor; Biochem and Molecular Biology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2001; Project Start 01-JAN-1982; Project End 31-MAR-2002 Summary: The primary goals of the current proposal involve a continuation of investigations designed to determine both the role of host and non-host proteinases in the development of lung-associated diseases as well as the mechanisms utilized to protect this organ against uncontrolled proteolytic events. In this context, the specific aims of the grant will involve a) detailed studies of the proteinases from mast cells, neutrophils, pollen, and bacteria which may be involved in the dysregulation of bronchial homeostasis through either the release of bradykinin and/or the degradation
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of vasoactive peptides, b) examination of the role of cytokines in the increased expression of proteinase inhibitors from hepatocytes, epithelial cells, and astrocytes during the acute phase proteinase response to inflammation, c) determination of the mechanism of interactions of proteinase inhibitors (serpins) with host serine proteinases, and d) analysis of the structure of the tetramer/heparin complex required to form active, stable mast cell tryptase. All of these results should provide significant information as to the role(s) of host and non-host proteinases in the development of allergies, asthma, bronchitis, and emphysema. In addition, a clearer understanding of the mechanisms for both increased proteinase inhibitor synthesis and regulation of host proteinases should be forthcoming. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONS
REGULATION
OF
CHEMOKINE
MEDIATED
LEUKOCYTE
Principal Investigator & Institution: Richardson, Micheler R.; Associate Professor; Biochemistry; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-JAN-2007 Summary: (provided by the applicant): Chemokines are inflammatory mediators of the chemotactic and cytotoxic functions of a large variety of cells including neutrophils, monocytes, eosinophils, basophils and lymphocytes. These functions are initiated through interaction with specific cell surface G-protein coupled receptors (GPCRs). Most chemokines activate more than one receptor on leukocytes. The hypothesis that underlies this application is that since multiple chemokines are present at sites of inflammation, the chemokine receptors activities must be tightly regulated to prevent tissue damage. We have developed a cellular model, a rat basophilic leukemia cell line (RBL-2H3), in which chemokine receptors can be singly or multiply expressed to display many leukocytes activities. These studies have provided striking evidence that these receptors cross-regulate each other?s function at multiple steps. Signal duration and protein kinase C (PKC) activation have been shown to be critical for receptor crossregulation. Studies in phagocytes and mouse models of peritoneal and skin inflammation have shown a complexity of cross-regulation among interleukin-8 (IL-8) and RANTES. This complexity likely reflects the ability of these chemokines to activate multiple receptors in leukocytes. The overall objective of this application is to elucidate the mechanism(s) of cross-regulation among the receptors for IL-8 (CXCR1 and CXCR2) and RANTES (CCR1 and CCR5) and to identify specific molecular targets in the signaling pathways, which modulate their ability to mediate and undergo crossdesensitization. Mechanisms of cross-desensitization will be investigated by determining the role of different protein kinase C (PKC) isozymes in receptor crossphosphorylation. The hypothesis that arrestin-mediated receptor internalization modulate signal duration will also be tested in beta arrestin deficient mice. Chemokines are involved in many acute and chronic inflammatory diseases such as rheumatoid arthritis, emphysema, cystic fibrosis, chronic bronchitis and bronchiectasis and proliferation of tumor malignant melanoma cells. Understanding the molecular mechanisms governing the regulation of chemokine will aid in understanding the control of inflammation as well as the etiology of many inflammatory disorders. These studies will also identify specific targets for the development of therapeutic drugs for the modulation of inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF MUCOUS CELL METAPLASIA IN ASTHMA Principal Investigator & Institution: Tesfaigzi, Yohannes; Staff Scientist; Lovelace Biomedical & Environmental Res Environmental Research Inst Albuquerque, Nm 87185 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Clinical manifestations of asthma result in part from chronic inflammation that leads to mucous cell metaplasia (MCM), the appearance of mucous cells in peripheral airways that are normally devoid of these cells. In a mouse model of asthma, systemic immunization with ovalbumin (OVA) followed by repeated exposures to OVA aerosols initially induces inflammation and MCM, while prolonged exposures cause increase of IFNgamma levels and resolution of MCM. Instillation of IFNgamma in allergen-exposed mice induces expression of Bax, a pro-apoptotic protein, and accelerates the resolution of MCM by causing apoptosis. Mice deficient in Bax or Stat 1, an obligatory signaling molecule for IFNgamma, do not resolve MCM during prolonged exposures to allergen. IL-13 inhibits IFNgamma-induced Bax expression and apoptosis in mucous cells of mice and in normal human bronchial epithelial cells (HBEs). Our guiding hypothesis is that IL-13 induces MCM and counteracts the role of IFNgamma to activate Stat 1 and induce apoptosis through a Bax-mediated pathway in metaplastic mucous cells. In Aim 1, we will determine the pathway by which IL-13 inhibits IFNgamma signaling and Bax mediated resolution of MCM. We will determine whether IL-13 directly inhibits Bax expression or activates Stat 3, which is known to cause expression of anti-apoptotic proteins, Bcl-2 and BcI-lxL. Furthermore, we will determine whether IL-13 requires signaling through IL-4Ralpha and Stat 6 to inhibit IFNgamma-induced Bax expression. In Aim 2, we will determine the pathway by which IFNgamma induces Bax expression in allergen-induced MCM and whether the Baxmediated pathway is essential to resolve MCM. We will investigate whether IFNgamma signals through IFN(R and Stat 1 to induce Bax in allergen-induced MCM and whether IFN( induces surface expression of IL-13Ralpha2 to inhibit IL-13 signaling through Stat 6. We will determine the requirement of Bax in decreasing MCM by instilling IFNgamma in Bax-deficient mice that have allergen-induced MCM. Our preliminary results with human autopsy tissues and bronchial brushings show that Bax is expressed in mucous cells from non-asthmatics and is absent in asthmatics. Therefore, in Aim 3, we will determine whether inflammatory mediators from asthmatics suppress expression of Bax and enhance mucous cell survival. The difference in the percentages of Bax-expressing cells among subjects with asthma, chronic bronchitis, and controls without respiratory diseases will be investigated using autopsy tissues and bronchial brushings. Furthermore, we will determine the effect of bronchoalveolar lavage fluid in inducing MCM and Bax expression in HBEs. These studies will provide new strategies to reduce mucous cell numbers in asthmatic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF NA/CL/K COTRANSPORT IN TRACHEAL EPITHELIUM Principal Investigator & Institution: Liedtke, Carol M.; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2002 Summary: Basolateral Na-K-CI cotransport (NKCC) in lining epithelial cells of the lung is crucial for optimal mucociliary clearance because it supplies CI for fluid secretion. Disease states that disrupt CI and fluid movement, such as asthma, chronic bronchitis, and cystic fibrosis (CF), and exposure to foreign irritants contribute to excess mucus and
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abnormal mucocillary clearance. Treatments aimed at correcting deficient CI secretion might fail to activate NKCC or might compromise NKCC activity thus preventing CI secretion and ultimately failing to correct excess mucus accumulation. Hence, in this proposal, we pose the question: how is NKCC turned on to support transepithelial CI secretion? New evidence from this laboratory points to protein kinase C (PKC)dependent activation of NKCC in tracheal epithelial cells (TEC) by hormone (alpha1adrenergic (AR)) stimulation and by hyperosmotic stress. However, modulation of NKCC is more complicated than activation of PKC. Although, intracellular CI levels (CIi) are depicted in models of NKCC to directly modulate CI flux across a plasma membrane through a CI electrochemical gradient, in TEC, stimuli that are expected to increase CIi activate NKCC. Preliminary studies strongly implicate an intracellular signalling pathway as a focal point for CI-dependent activation of NKCC. This will be studied in detail in the following specific aims: 1) To test the hypothesis that CIi modulates NKCC activation by alpha1-AR agonist or by hyperosmotic stress. Changes in [CI]i induced by the two stimuli will be determined. CIi levels will be manipulated to study subsequent effects on activation of NKCC and on NKCC activity. The kinetics of NKCC deactivation will be investigated. 2) To test the hypothesis that CIi modulates activity of protein kinases and phosphatases required for modulation of NKCC activity. Altered activity of protein kinases and phosphatases and the CI-dependence of the enzyme activities will be studied using specific substrates, including NKCC from human and kidney. stPP isotype(s) required for deactivation of NKCC will be identified. 3) To test the hypothesis that CIi modulates protein-protein interactions between NKCC and PKC and/or protein phosphatases. Protein-protein interaction and its dependence on [CI] and activated enzyme will be investigated using immunopurified NKCC, PKC, and protein phosphatases. Shifts in in vivo localization of enzymes with stimulation will be determined by confocal microscopy. A long term outcome of this project is the development of pharmacological tools to manipulate protein-protein interactions that facilitate association of PKC and NKCC to modulate NKCC activity in pathophysiological states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF THE STIMULATION OF MUCIN GENE EXPRESSION Principal Investigator & Institution: Koo, Ja S.; Thoracic Head/Neck Med Oncol; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-JUL-2004 Summary: (Taken from the Candidate's Abstract) Acute or chronic exposure of environmental insults and toxicants trigger inflammatory pulmonary conditions, resulting in infiltration of inflammatory cells and elevation of inflammatory mediators, and alteration of the integrity and function of the airway epithelium. Hypersecreted visco-elastic mucus causes obstruction of central and peripheral airways in many inflammatory airway diseases such as asthma, cystic fibrosis, chronic bronchitis, and bronchiectasis. Inhibition of over expressed pathophysiologic mucus is one of the major targets for treatments of airway inflammatory disorders. Previously, the candidate has shown that tetinoic acid (RA), a key element required for mucous cell differentiation, mucin production, and mucin gene expression is mediated through retinoic acid receptor alpha. Based on these findings, the candidate hypothesizes that repressing receptor alpha activity will inhibit over expression of mucin gene mRNAs and mucin hypersecretion induced by inflammatory mediators. The specific aims are to clarify: 1) the biochemical mechanisms by which inflammatory mediators increase the expression
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of mucin gene mRNAs and mucin secretion; 2) the molecular mechanisms by which receptor alpha signaling pathway regulate inflammatory mediators-increased mucin production; and, 3) the molecular mechanisms of a cross-talk between receptor alpha and IL-1 beta signaling pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESPONSE OF INFLAMMATION PRIMED LUNG CELLS TO PARTICLES Principal Investigator & Institution: Kobzik, Lester; Associate Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001 Summary: The Problem: Particulates within air pollution are associated with significant morbidity and mortality at commonly encountered ambient concentrations. The biologic basis for their health effects is unknown, but the same epidemiologic studies which reveal particle effects also offer an important clue. Harmful health effects occur most notably among individuals with pre-existing respiratory disease, e.g. chronic bronchitis and asthma, indicating a heightened sensitivity to particle effects within inflammed lungs. Experimentally, we have found that inhalation exposure of animals to "realworld" concentrated ambient particulates (CAPs) prepared via a novel technology causes toxic effects--but only in animals with pre-existing pulmonary inflammation (asthma, SO2, bronchitis), and not in healthy controls. Hypothesis: The central thesis of this proposal is that pre-existing pulmonary disease alters or "primes" the lung's response to inhaled ambient particles, resulting in increased inflammation and health effects. We further postulate that oxidative stress mediated by particulate components is a central mechanism for increased production of inflammatory mediators by "primed" lung cells. Experimental Plan: In specific Aim #1 we will measure in vitro the production of reactive oxygen species, nitric oxide and cyrokines in response to uptake of CAPs by lung marcophages or epithelial cells with or without "priming" by inflammatory mediators (LPS, TNF). We will test our hypothesis regarding oxidant mechanisms of CAPs effects by: 1) measuring oxidant stress in primed and normal lung cells after uptake of CAPs (oxidation of intracellular reporter DCFH; lipid peroxidation); 2) analyzing oxidant components (e.g. SiO2, Fe) in samples of CAPs that vary in inflammatory effects; 3) testing the ability of antioxidants to block cellular responses. In specific Aim #2 we will characterize in vivo the effects of inhaled concentrated ambient particulates (CAPs) on pre-existing inflammatory lung disease using a mouse asthma model. We will test our hypotheses by inhalation exposure of normal and "asthmatic" mice to CAPs, measuring both lung lavage markers of cellular inflammation (total cells, number of eosinophils, cytokine levels) and physiologic tests of airway bronchoconstriction. To complete our study of mechanisms in vivo, we will also measure the effects of antioxidant intervention, both pharmacologic and through use of genetically altered mice. Significance: The proposed studies will determine mechanisms for the effect of air pollution particulates. Such informaiton is critical to public health management of this problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF A NEUTROPHIL INTEGRIN IN LUNG INFLAMMATION Principal Investigator & Institution: Sheppard, Dean C.; Director, Lung Biology Center; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122
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Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 30-NOV-2003 Summary: Neutrophils contribute to the tissue injury central to a number of common lung diseases, including acute lung injury, cystic fibrosis and chronic bronchitis. A key step in the development of neutrophil-mediated tissue injury is the recruitment of neutrophils to sites of extravascular injury. Although several of the critical receptors involved in the recruitment of neutrophils have been identified, considerable evidence suggests that unidentified receptors must participate in neutrophil recruitment, especially recruitment into the lung. Recently, we have identified the integrin alpha9beta1 on human neutrophils, and have found that this integrin together with its close structural relative, alpha4beta1, is critical for neutrophil migration across activated endothelial monolayers in vitro. The central issues addressed in this application are the mechanisms by which alpha9beta1 in the distinct steps of rolling, stable adhesion and endothelial transmigration, we will utilize blocking monoclonal antibodies and neutrophils derived from the bone marrow of alpha9 null chimeric mice. To determine the in vivo significance of alpha9beta1 on neutrophils we will examine neutrophil sequestration, extra-vascular emigration and neutrophil-mediated tissue injury in the lungs and peritoneal cavity in guinea pigs treated with alpha9beta1 blocking antibody and in chimeric mice with alpha9 null neutrophils. We will then utilize cell lines stably transfected with a variety of deletion and chimeric mutant versions of alpha9 to determine the role of specific sequences in the alpha9 and alpha4 cytoplasmic domains in adhesion, migration and endothelial transmigration. Finally we will utilize ch8imeric and mutant forms of alpha9 with defined functional properties to determine the roles of rapid spatial redistribution of integrins and cytoskeletal associations in integrinmediated migration, both in leukocyte and non-leukocyte model systems. These studies should provide insight into key steps in neutrophil recruitment and could lead to the development of novel interventions for the treatment of diseases characterized by neutrophil-mediated tissue injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMOKE INDUCED MUCIN TRANSCRIPTION AND MITOGENESIS Principal Investigator & Institution: Basbaum, Carol B.; Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-JUL-2003 Summary: The mechanisms by which tobacco smoke cause chronic bronchitis and lung cancer are unknown. Clues are provided, however, by our recent findings showing that smoke directly induces mucin mRNA and mitogenesis in lung epithelial cells and that this is preceded by activation of Src kinase and phosphorylation of the EGF receptor (EGFr). Src kinase inhibitors abrogate smoke-induced EGFr phosphorylation, mucin transcription induction and mitogenesis. EGFr kinase inhibitors abrogate smokeinduced EGFr phosphorylation and mitogenesis but only partially block mucin transcriptional upregulation. This leads us to hypothesize that smoke activates a branched signaling pathway emanating from Src kinase. One arm of the pathway is EGFr-dependent and is sufficient to account for smoke-induced mitogenesis; the other is EGFr-independent and its effects summate with those of the other branch to mediate mucin transcription. The experiments described in this proposal will provide information regarding both the EGFr-dependent and -independent signaling pathways. In experiments described under Specific Aim I, we will identify EGFr-interacting elements of the smoke-signaling pathway leading to (a) mucin induction and (b) mitogenesis. In experiments described under Specific Aim II, we will identify Srcinteracting elements of the smoke signaling pathway leading to (a) mucin induction and
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(b) mitogenesis. In experiments described under Specific Aim III, we will identify components of smoke responsible for activating (a) mucin induction and (b) mitogenesis. The results of these studies should reveal control points amenable to inhibition by pharmacological agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPITHELIUM
SPATIOTEMPORAL
NITRIC
OXIDE
SIGNALING,
AIRWAY
Principal Investigator & Institution: Boitano, Scott; Assistant Professor; University of Wyoming Box 3355, University Station Laramie, Wy 82071 Timing: Fiscal Year 2001 Summary: (Adapted from the applicant's abstract): The airway epithelium is an active cellular layer with ciliary movement to clear materials, the ability to secrete inflammatory effectors, and a biological barrier function that helps protect against pathogenic microorganisms, foreign insults and injury. Compromise of the upper airway epithelium and exposure of the underlying tissue has been associated with many pulmonary diseases, including asthma, bronchitis, and chronic obstructive pulmonary distress syndrome as well as the increased susceptibility to pathogenic microorganisms, which further exacerbates these and other airway diseases. Maintenance of a healthy airway epithelium is through a complicated series of second messenger signaling and communication. Nitric Oxide (NO) is one signaling molecule used in the airway that can have both beneficial and detrimental effects. In this study, primary cultures of airway epithelial tissue and the airway pathogen, Bordetella bronchiseptica, will be used as model systems to elucidate distinct spatiotemporal release of NO by airway epithelial cells as a controlled response to local insults to help defend against cell and tissue damage or as a uncontrolled response that can cause airway cellular damage and allow for progression of airway disease. Established methods in NO research will be used to identify cellular and enzymatic source(s) of NO production in cultured tracheal airway epithelial cells, elucidate the role(s) for NO in Bordetella bronchiseptica cell pathogenesis and determine the bacteriostatic role for NO in airway protection following wounding. Additionally, new NO probes will be used to characterize unique spatiotemporal changes in cellular NO concentration that may elucidate its shift from a preventative to a damaging agent in the airway epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T CELL CONTROL OF AIRWAY MUCUS PRODUCTION Principal Investigator & Institution: Cohn, Lauren E.; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Mucus hyperproduction contributes to morbidity and mortality in patients with chronic airway diseases. In asthma, chronic bronchitis and cystic fibrosis, inflammation is believed to stimulate mucus production, despite their different characteristic airway pathologies. We have defined two inflammatory pathways that lead to mucus production, using a murine system we developed to study the inflammatory effects of Th1 and Th2 cells in the respiratory tract. Th2 cells activated in the airways of mice stimulate airway eosinophilia, airway hyperresponsiveness and mucus production; features found in asthmatic patients. We show that mucus induction by Th2 cells does not require IL-4, IL-5, eosinophils or mast cells, but depends on signaling through IL-4Ralpha, the common chain in IL-13 and IL-4 receptors. Thus, it
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appears that IL-13 stimulates mucus production induced by Th2 cells. We also show that mucus can be induced by a mechanism that is Th2-independent and associated with airway neutrophilia, suggesting some of the features in chronic bronchitis and cystic fibrosis. We present novel studies showing that Th1 cells, through the production of IFNgamma, inhibit mucus production induced by both Th1 and Th2 cells. Furthermore, IFNgamma produced by Th1 cells has the potential to reduce airway pathology in immunotherapy of asthma. Our goals in this proposal are to gain a more complete understanding of the cellular and molecular mechanisms that regulate mucus production. Our aims are to 1) determine the mechanism by which CD4 Th cells stimulate mucus production; 2) determine how airway epithelial mucus production is inhibited by IFNgamma 3) determine the extent of inhibitory effects of IFNgamma on mucus production. Using our established adoptive transfer system in which Th1 and Th2 cells and recipient mice can be independently genetically manipulated, the precise factors important in the control of mucus production will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE VASCULAR BIOLOGY OF LUNG PRESERVATION Principal Investigator & Institution: Pinsky, David J.; Professor and Scientific Director; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: Nitric oxide (NO) levels plummet precipitously after lung transplantation (LTX), due to quenching by superoxide (O2-) in the reperfusion milieu. This can lead to graft thrombosis, leukostasis, and primary graft failure. In biological systems, however, alternative pathways are often activated when a primary homeostatic pathway fails, to contain the damage. Using a novel porphyrinic sensor capable of specifically detecting carbon monoxide (CO), we show that this diatomic gas which, like NO, binds to and activates heme-containing proteins, is produced at high levels in lungs subjected to ischemic stress at a time when NO levels plummet. CO given to rat LTX donors prior to lung harvest markedly improves posttransplant graft function and recipient survival. Heme oxygenase (HO) type 1, which catabolizes heme to liberate CO in vivo, is induced by ischemic stress. Mice null for the HO-1 gene exhibit exaggerated lung injury in response to ischemia but are rescued from ischemic lung injury by CO inhalation. Mechanistically, CO appears to restore vascular homeostasis by suppressing endothelial cell apoptosis in response to oxidant stress and by preventing ischemic induction of plasminogen activator inhibitor-1(PAI-1), thereby potentiating lysis of thrombus in postischemic microvessels. These data lead us to hypothesize that lung ischemia or preservation triggers expression of HO-1, which drives CO production to reestablish protective vascular homeostasis. The aims of the current proposal are (1) to elucidate the functional role of endogenous HO-1 and CO in lung ischemia and transplantation; (2) to elucidate the mechanism(s) by which CO protects the ischemic lungs; and (3) to determine whether early HO-1/CO induction may limit the late development of obliterative after LTX. Studies will use orthotopic rat LTX and murine tracheal allograft models, HO-1 and PAI-1 gene-deleted mice (and endothelial cells derived therefrom) with or without reconstitution with CO, and unique CO/NO/O2- porphyrinic sensor technology to describe a novel HO- 1/CO mediated axis of ischemic pulmonary protection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANS-MEMBRANE WATER AND ION MEASUREMENT SYSTEM (TWIMS) Principal Investigator & Institution: Wong, Lid B.; Chief Scientific Officer; Biotechplex Corporation 755 Nicholas Blvd Elk Grove Village, Il 60007 Timing: Fiscal Year 2003; Project Start 30-SEP-2000; Project End 30-JUN-2005 Summary: (provided by applicant): BioTechPlex proposes to develop a Transmembrane Water and Ion Measurement System (TWIMS) to measure miniscule water fluxes across biological membranes in conjunction with their electro-physiological properties. BioTechPlex has accomplished all the objectives proposed in Phase I. A) Developed a novel light source and associated optics for fluorescence photon detection and analysis. B) Integrated the bench optics into a measurement system, tested the system and demonstrated its markedly increased sensitivity for the measurement of transmembrane water fluxes. In this Phase II project, BioTechPlex will integrate the principle and concepts of the electro-optics developed in this Phase I to build an 8-tissue chamber system. To develop a manufacturability prototype of the TWIMS, we will proceed with the development of further innovative technologies. These include: 1) fluorescence detection technology; 2) prototyping of the chambers and tissue holders to accommodate both native epithelia and confluent tissue cultures; and 3) a virtual instrumentation platform for the measurement of luminal to basolateral and basolateral to luminal waters fluxes, potential difference and short circuit current. This multichamber system will be designed to suit the needs of physiologists and pharmacologists, in academia, government and industry. It will be designed for scientific research experiments as well as for use in the drug discovery industry. BioTechPlex plans to market the TWIMS for scientific investigations and drug discovery in fields including but not limited to, 1) respiratory disease such as chronic bronchitis, asthma bronchiectasis and cystic fibrosis; 2) gastrointestinal disease such as diarrhea, cholera infection and severe dehydration; 3) kidney disease such as renal failure; and 4) eye diseases such as dry eye syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIAL TO REDUCE ANTIBIOTIC USE IN A PRIMARY CARE PBRN Principal Investigator & Institution: Bates, David W.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Background: Upper respiratory tract infections (URIs) are the number one reason for prescribing antibiotics in the United States. Most antibiotic prescribing for URIs is done in primary care and much antibiotic prescribing for URIs is inappropriate. Inappropriate antibiotic prescribing exposes patients to unnecessary medication, increases the prevalence of antibiotic-resistant bacteria, and increases medical costs. Interventions are needed to reduce inappropriate antibiotic prescribing for URIs in primary care. The PBRN: The Brigham and Women's Primary Care Practice-Based Research Network (BWPC-PBRN) consists of 12 ambulatory clinics with 95 physicians who serve a socioeconomically and ethnically diverse patient population. The BWPC-PBRN had 237,530 total patient visits and had 17,443 visits for URIs in 2002. BWPC clinics are linked organizationally and electronically with e-mail and the use of a common electronic medical record that allows linkage of diagnostic, prescribing, and other clinical data. Research Plan: We propose to develop and evaluate a novel electronic medical record-based URI-care template in the BWPC-PBRN through two specific aims. Specific aim 1 is to design and implement an electronic medical
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record-based template for the care of patients with URIs in primary care practice, the URI Smart Set. The URI Smart Set will include easy documentation in the form of checkboxes for symptoms and physical findings; automatic importation of patients' problems, allergies, and medications; decision-support for the treatment of sinusitis, pharyngitis, and acute bronchitis; printable patient handouts about URIs, self-care, and antibiotics; and access to relevant medical literature. Specific aim 2 is to test the implementation of the URI Smart Set in a randomized, controlled trial. Following a baseline period, 18 practices within the BWPC-PBRN will be randomized to control status or to the use of the URI Smart Set. The primary outcome will be antibiotic prescribing for URIs during a six-month period. Secondary outcomes will be the appropriateness of antibiotic prescribing, 30-day repeat visits, antibiotic costs, and barriers to the use of the URI Smart Set. Future Directions: Longer term goals of this research include optimization of the usability and functionality of the URI Smart Set; serving as a prototype for standardizing documentation for other clinical problems in primary care; rapidly identifying patients who potentially meet criteria for inclusion in future trials of therapy in URI care; and providing real-time surveillance for bioterrorist attacks or the emergence of novel respiratory pathogens, such as severe acute respiratory syndrome (SARS). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRUS INDUCED CYTOKINE PRODUCTION BY HUMAN AIRWAY EPITHELIUM IN VIVO/IN VITRO Principal Investigator & Institution: Noah, Terry L.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001 Summary: Respiratory syncytial virus (RSV)-induced acute wheezing syndromes produce great morbidity among children. Inflammation is probably a key factor in the pathogenesis of wheezing, but the inflammatory pathways resulting in virus-induced wheezing are unknown. RSV induces production of the chemokines IL-8 and RANTES by respiratory epithelial cells in culture. These chemokines are potent chemotactic or priming agents for leukocytes which may cause bronchospasm, edema, and airway hyperreactivity. We hypothesize that individuals who wheeze during RSV infection have greater respiratory epithelia chemokine production than those who do not wheeze during viral infections. Nasal epithelium is susceptible to RSV infection and can be sampled noninvasively in children, and available evidence suggests that nasal inflammation reflects or influences the lower airway in humans. We therefore propose a series of studies which will determine nasal epithelial chemokine responses to RSV and their relationship to inflammation, memory T cell responses, and wheezing. The specific aims of this proposal are to determine (1) the time course of, cellular sources of, and effects of antiinflammatory agents on epithelial chemokine production during human RSV respiratory illnesses; (2) the nasal epithelial subtypes and infection status of the cells producing chemokines during RSV infections; (3) if the nasal chemokine and/or memory T lymphocyte cytokine responses to RSV differ between children who do vs. Do not manifest wheezing with RSV infection; and (4) if RSV-induced chemokine responses by nasal epithelial cells are greater in cells cultured from subjects with vs. Without recurrent wheezing. Studies will include serial nasal lavage and mucosal biopsies obtained from children with naturally-acquired RSV infections and from adults with experimental RSV infections. Chemokine production and cell types of origin in respiratory mucosa will be determined using a combination of ELISA, RT-PCR, and immunohistochemistry. In experimental RSV infections of adults, the effects of topical
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antiinflammatory agents on nasal inflammation and chemokine production will be determined. Production of cytokines by cultured T lymphocytes stimulated with RSV antigens will be measured by RT-PCR, in situ hybridization, and ELISA. Nasal epithelial cell cultures established from subjects with and without recurrent wheezing will be infected with RSV for comparison of chemokine induction responses. These studies will establish the kinetics of RSV-induced epithelial chemokine induction in the upper respiratory tract, its relationship to common acute childhood wheezing syndromes, and the relative degree to which epithelial and T lymphocyte cytokine responses correlate with susceptibility for wheezing with acute RSV infection. Definition of specific epithelium-driven inflammatory pathways triggered by RSV infections should lead to identification of future therapies or preventive strategies for RSV-induced respiratory illnesses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRUS-INDUCIBLE REMODELING OF AIRWAY EPITHELIUM Principal Investigator & Institution: Holtzman, Michael J.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The long-term goal of this proposal is to understand how viral respiratory infections lead to asthma. In that context, we have proposed that airway epithelial cells (the viral host cells) may be specially programmed for normal immune defense and abnormally programmed in asthma. The current proposal is based on new findings related to regulation of airway epithelial cell death/desquamation and proliferation/renewal in the context of viral infections relevant to asthma. Thus, in studies of isolated cells, we found distinct behavior for respiratory syncytial virus (RSV)- (and surface receptor-) inducible death that came with mitochondrial dysfunction (likely mediated by BCL-2 family proteins) even without activation of apoptosis-related endoproteases (caspases). In these studies, RSV-inducible cell death was also coined to a proliferative response that was marked by a subpopulation of hyperproliferating airway epithelial cells. The pathophysiologic impact of these findings became evident in studies of mice, when we found that paramyxoviral infection (using Sendai virus) caused epithelial cell death during the acute tracheobronchitis, but then led to unchecked airway epithelial proliferation/hyperplasia with striking remodeling/thickening of the airway epithelium and concomitant bronchial hyperreactivity. The airway epithelial remodeling and hyperreactivity persisted for at least a year after the acute tracheobronchitis was resolved, and was marked by increased epithelial expression of the cell survival factor BCL-2. To our knowledge, these models form the initial basis for a link between primary paramyxovirus infection and the subsequent development of long-lasting airway epithelial remodeling and hyperreactivity. In this setting, we propose that virus-inducible cell death depends on acute mitochondrial events (with activation of pro-apoptotic BCL-2 family proteins) whereas hyperplasia may depend on prolonged cell survival (driven by chronic overexpression of anti-apoptotic BCL-2) in combination with cell proliferation. Proliferating cells must move from G to S phase of the cell cycle, and this step requires inactivation of retinoblastoma (Rb) or Rb-related proteins. We suggest that viral replication flips a molecular switch in the BCL-2-regulated cell death and Rb regulated proliferation pathways that may last far beyond the initial acute infection and in this model appears to last for the life of the animal. We now aim to further define the molecular basis for the distinct death and proliferative capacities of airway epithelial cells exhibited in response to paramyxoviral infection using a combined in vitro and in
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vivo approach. Accordingly, we propose to: (I) Define the molecular components that mediate RSV-inducible death and proliferation in primary-culture human airway epithelial cells focusing on specific determinants of cell survival (i.e., BCL-2 family proteins) and cell cycle control (i.e., Rb- and Rb-related proteins); and (II) Determine the role of these same cell survival and cell cycle regulatory factors in epithelial remodeling and airway hyperreactivity in a mouse model of paramyxoviral tracheobronchitis using wild-type and genetically-modified mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “bronchitis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bronchitis in the PubMed Central database: •
Acute bronchitis and clinical outcome three years later: prospective cohort study. by Jonsson JS, Gislason T, Gislason D, Sigurdsson JA.; 1998 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28724
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Analysis of the serotype-specific epitopes of avian infectious bronchitis virus strains Ark99 and Mass41. by Jia W, Wang X, Parrish CR, Naqi SA.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190784
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Characterization in vitro of an autocatalytic processing activity associated with the predicted 3C-like proteinase domain of the coronavirus avian infectious bronchitis virus. by Tibbles KW, Brierley I, Cavanagh D, Brown TD.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190021
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cis-Acting Sequences Required for Coronavirus Infectious Bronchitis Virus Defective-RNA Replication and Packaging. by Dalton K, Casais R, Shaw K, Stirrups K, Evans S, Britton P, Brown TD, Cavanagh D.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113905
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Effectiveness of short-course therapy (5 days) with cefuroxime axetil in treatment of secondary bacterial infections of acute bronchitis. by Henry D, Ruoff GE, Rhudy J, Puopolo A, Drehobl M, Schoenberger J, Giguere G, Collins JJ.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162978
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Efficacy and Safety of a 10-Day Course of 400 or 600 Milligrams of Grepafloxacin Once Daily for Treatment of Acute Bacterial Exacerbations of Chronic Bronchitis: Comparison with a 10-Day Course of 500 Milligrams of Ciprofloxacin Twice Daily. by Chodosh S, Lakshminarayan S, Swarz H, Breisch S.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105465
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Endobronchial inflammation following Pseudomonas aeruginosa infection in resistant and susceptible strains of mice. by Morissette C, Skamene E, Gervais F.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173215
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Identification of a Novel Cleavage Activity of the First Papain-Like Proteinase Domain Encoded by Open Reading Frame 1a of the Coronavirus Avian Infectious Bronchitis Virus and Characterization of the Cleavage Products. by Lim KP, Ng LF, Liu DX.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111642
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In Vitro and In Ovo Expression of Chicken Gamma Interferon by a Defective RNA of Avian Coronavirus Infectious Bronchitis Virus. by Hackney K, Cavanagh D, Kaiser P, Britton P.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154032
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Induction of Caspase-Dependent Apoptosis in Cultured Cells by the Avian Coronavirus Infectious Bronchitis Virus. by Liu C, Xu HY, Liu DX.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114363
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Infectious Bronchitis Virus E Protein Is Targeted to the Golgi Complex and Directs Release of Virus-Like Particles. by Corse E, Machamer CE.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111949
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Longitudinal study of childhood wheezy bronchitis and asthma: outcome at age 42. by Horak E, Lanigan A, Roberts M, Welsh L, Wilson J, Carlin JB, Olinsky A, Robertson CF.; 2003 Feb 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149441
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Membrane Association and Dimerization of a Cysteine-Rich, 16-Kilodalton Polypeptide Released from the C-Terminal Region of the Coronavirus Infectious Bronchitis Virus 1a Polyprotein. by Ng LF, Liu DX.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136229
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Pharmacokinetics of [18F]fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography. by Fischman AJ, Livni E, Babich JW, Alpert NM, Bonab A, Chodosh S, McGovern F, Kamitsuka P, Liu YY, Cleeland R, Prosser BL, Correia JA, Rubin RH.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163176
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Proteolytic processing of the coronavirus infectious bronchitis virus 1a polyprotein: identification of a 10-kilodalton polypeptide and determination of its cleavage sites. by Liu DX, Xu HY, Brown TD.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191251
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Reducing antibiotic use for acute bronchitis by giving patients written information. by Farquhar D.; 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99458
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Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet. by Macfarlane J, Holmes W, Gard P, Thornhill D, Macfarlane R, Hubbard R.; 2002 Jan 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64506
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Replication and packaging of coronavirus infectious bronchitis virus defective RNAs lacking a long open reading frame. by Penzes Z, Wroe C, Brown TD, Britton P, Cavanagh D.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190960
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Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus. by Casais R, Thiel V, Siddell SG, Cavanagh D, Britton P.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116132
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Specific cytotoxic T lymphocytes are involved in in vivo clearance of infectious bronchitis virus. by Seo SH, Collisson EW.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191752
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The carboxyl-terminal 120-residue polypeptide of infectious bronchitis virus nucleocapsid induces cytotoxic T lymphocytes and protects chickens from acute infection. by Seo SH, Wang L, Smith R, Collisson EW.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192145
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The Coronavirus Infectious Bronchitis Virus Nucleoprotein Localizes to the Nucleolus. by Hiscox JA, Wurm T, Wilson L, Britton P, Cavanagh D, Brooks G.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113943
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The Cytoplasmic Tail of Infectious Bronchitis Virus E Protein Directs Golgi Targeting. by Corse E, Machamer CE.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135861
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 bronchitis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “bronchitis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for bronchitis (hyperlinks lead to article summaries): 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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“Plastic bronchitis” complicating recovery from congenital heart surgery. Author(s): Setzer N, Malvezzi L, McBride W. Source: The Journal of Pediatrics. 2001 April; 138(4): 605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295733&dopt=Abstract
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15(S)-HETE modulates LTB(4) production and neutrophil chemotaxis in chronic bronchitis. Author(s): Profita M, Sala A, Riccobono L, Pace E, Paterno A, Zarini S, Siena L, Mirabella A, Bonsignore G, Vignola AM. Source: American Journal of Physiology. Cell Physiology. 2000 October; 279(4): C124958. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11003605&dopt=Abstract
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A comparative study of clarithromycin modified release and amoxicillin/clavulanic acid in the treatment of acute exacerbation of chronic bronchitis. Author(s): Martinot JB, Carr WD, Cullen S, Heredia Budo JL, Bauer K, MacLeod C, Sanguinetti CM, van Veldhuizen WC; Clarithromycin Once-a-Day Study Group. Source: Adv Ther. 2001 January-February; 18(1): 1-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11512528&dopt=Abstract
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A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes. Author(s): Wilson R, Schentag JJ, Ball P, Mandell L; 068 Study Group. Source: Clinical Therapeutics. 2002 April; 24(4): 639-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017408&dopt=Abstract
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A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis. Author(s): Schaberg T, Ballin I, Huchon G, Bassaris H, Hampel B, Reimnitz P; AECB Study Group. Source: J Int Med Res. 2001 July-August; 29(4): 314-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675905&dopt=Abstract
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Acute bronchitis imaged with F-18 FDG positron emission tomography. Author(s): Kicska G, Zhuang H, Alavi A. Source: Clinical Nuclear Medicine. 2003 June; 28(6): 511-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917540&dopt=Abstract
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Acute exacerbation of chronic bronchitis: disease-specific issues that influence the cost-effectiveness of antimicrobial therapy. Author(s): Saint S, Flaherty KR, Abrahamse P, Martinez FJ, Fendrick AM. Source: Clinical Therapeutics. 2001 March; 23(3): 499-512. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318083&dopt=Abstract
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Acute exacerbation of chronic bronchitis: what is the clinical significance of pathogenic bacteria in sputum cultures? Author(s): Watanakunakorn C. Source: Chest. 2000 December; 118(6): 1523-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115428&dopt=Abstract
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Acute exacerbations of chronic bronchitis: a pharmacoeconomic review of antibacterial use. Author(s): Morris S, Anderson P, Irwin DE. Source: Pharmacoeconomics. 2002; 20(3): 153-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929346&dopt=Abstract
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Acute exacerbations of chronic bronchitis: what role for the new fluoroquinolones? Author(s): Obaji A, Sethi S. Source: Drugs & Aging. 2001; 18(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232735&dopt=Abstract
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Acute sore throat and bronchitis. How effective are antibiotics? Author(s): Mant A. Source: Aust Fam Physician. 2000 September; 29(9): 860, 879. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008390&dopt=Abstract
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Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Author(s): Sethi S, Muscarella K, Evans N, Klingman KL, Grant BJ, Murphy TF. Source: Chest. 2000 December; 118(6): 1557-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115440&dopt=Abstract
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Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease. Author(s): Bresser P, Out TA, van Alphen L, Jansen HM, Lutter R. Source: American Journal of Respiratory and Critical Care Medicine. 2000 September; 162(3 Pt 1): 947-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10988111&dopt=Abstract
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Airway nitric oxide in infants with acute wheezy bronchitis. Author(s): Ratjen F, Kavuk I, Gartig S, Wiesemann HG, Grasemann H. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2000 November; 11(4): 230-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110577&dopt=Abstract
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An open-label, randomized, multicenter, comparative study of the efficacy and safety of 7 days of treatment with clarithromycin extended-release tablets versus clarithromycin immediate-release tablets for the treatment of patients with acute bacterial exacerbation of chronic bronchitis. Author(s): Weiss K, Vanjaka A; Canadian Clarithromycin Study Group on Bronchitis. Source: Clinical Therapeutics. 2002 December; 24(12): 2105-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581548&dopt=Abstract
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Animal models of chronic bronchitis and their relevance to studies of particleinduced disease. Author(s): Nikula KJ, Green FH. Source: Inhalation Toxicology. 2000; 12 Suppl 4: 123-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881890&dopt=Abstract
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Antibiotic prescribing for acute bronchitis: how low can we go? Author(s): Hickner JM. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 November-December; 13(6): 462-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117346&dopt=Abstract
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Antibiotic prescribing for patients with colds, upper respiratory tract infections, and bronchitis: A national study of hospital-based emergency departments. Author(s): Stone S, Gonzales R, Maselli J, Lowenstein SR. Source: Annals of Emergency Medicine. 2000 October; 36(4): 320-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11020678&dopt=Abstract
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Antibiotic prescribing in ambulatory care settings for adults with colds, upper respiratory tract infections, and bronchitis. Author(s): Cantrell R, Young AF, Martin BC. Source: Clinical Therapeutics. 2002 January; 24(1): 170-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833830&dopt=Abstract
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Antibiotic therapy in acute exacerbations of chronic bronchitis. Author(s): Adams SG, Anzueto A. Source: Seminars in Respiratory Infections. 2000 September; 15(3): 234-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052424&dopt=Abstract
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Antibiotic treatment and baseline severity of disease in acute exacerbations of chronic bronchitis: a re-evaluation of previously published data of a placebo-controlled randomized study. Author(s): Allegra L, Blasi F, de Bernardi B, Cosentini R, Tarsia P. Source: Pulmonary Pharmacology & Therapeutics. 2001; 14(2): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273797&dopt=Abstract
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Antibiotic treatment of acute bronchitis in smokers: a systematic review. Author(s): Linder JA, Sim I. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2002 March; 17(3): 230-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929510&dopt=Abstract
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Antibiotics for acute bronchitis. Author(s): Arroll B, Kenealy T. Source: Bmj (Clinical Research Ed.). 2001 April 21; 322(7292): 939-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11312211&dopt=Abstract
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Antibiotics for acute bronchitis. Author(s): Smucny J, Fahey T, Becker L, Glazier R, McIsaac W. Source: Cochrane Database Syst Rev. 2000; (4): Cd000245. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034678&dopt=Abstract
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Antibiotics in the treatment of acute exacerbations of chronic bronchitis. Author(s): Dever LL, Shashikumar K, Johanson WG Jr. Source: Expert Opinion on Investigational Drugs. 2002 July; 11(7): 911-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084002&dopt=Abstract
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Are beta2-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systematic review. Author(s): Smucny JJ, Flynn CA, Becker LA, Glazier RH. Source: The Journal of Family Practice. 2001 November; 50(11): 945-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711010&dopt=Abstract
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Around PediHeart: plastic bronchitis. Author(s): McCarey F. Source: Pediatric Cardiology. 2002 March-April; 23(2): 151. Epub 2002 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889525&dopt=Abstract
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Aspergillus bronchitis causing atelectasis and acute respiratory failure in an immunocompromised patient. Author(s): Routsi C, Platsouka E, Prekates A, Rontogianni D, Paniara O, Roussos C. Source: Infection. 2001 August; 29(4): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545491&dopt=Abstract
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Aspergillus tracheobronchitis after allogeneic bone marrow transplantation. Author(s): van Assen S, Bootsma GP, Verweij PE, Donnelly JP, Raemakers JM. Source: Bone Marrow Transplantation. 2000 November; 26(10): 1131-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108318&dopt=Abstract
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Assessing patient outcomes in acute exacerbations of chronic bronchitis: the measure your medical outcome profile (MYMOP), medical outcomes study 6-item general health survey (MOS-6A) and EuroQol (EQ-5D). Author(s): Paterson C, Langan CE, McKaig GA, Anderson PM, Maclaine GD, Rose LB, Walker SJ, Campbell MJ. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2000; 9(5): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11190007&dopt=Abstract
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Assessment of the value of pHmetry results in diagnostics of gastroesphageal reflux as a cause of obstructive bronchitis in children. Author(s): Zielinska I, Czerwionka-Szaflarska M. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 March; 8(3): Cr169-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887030&dopt=Abstract
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Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Author(s): Hill AT, Campbell EJ, Hill SL, Bayley DL, Stockley RA. Source: The American Journal of Medicine. 2000 September; 109(4): 288-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10996579&dopt=Abstract
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Asthma in adult patients presenting with symptoms of acute bronchitis in general practice. Author(s): Thiadens HA, Postma DS, de Bock GH, Huysman DA, van Houwelingen HC, Springer MP. Source: Scandinavian Journal of Primary Health Care. 2000 September; 18(3): 188-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11097106&dopt=Abstract
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Asthma, chronic bronchitis and respiratory symptoms among adults in Estonia according to a postal questionnaire. Author(s): Meren M, Jannus-Pruljan L, Loit HM, Polluste J, Jonsson E, Kiviloog J, Lundback B. Source: Respiratory Medicine. 2001 December; 95(12): 954-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778792&dopt=Abstract
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Asthmatic bronchitis for 2 years. A case report. Author(s): Starakis I, Mylona M, Spyropoulos K, Dimopoulos PA. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2003 July; 44(4): 392-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846689&dopt=Abstract
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Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Author(s): Evans AT, Husain S, Durairaj L, Sadowski LS, Charles-Damte M, Wang Y. Source: Lancet. 2002 May 11; 359(9318): 1648-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020525&dopt=Abstract
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Azithromycin is effective in patients with chronic bronchitis. Author(s): Kopjar B. Source: The Journal of Antimicrobial Chemotherapy. 2002 September; 50(3): 433-4; Author Reply 434. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205072&dopt=Abstract
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Azithromycin versus pivampicillin in the treatment of acute exacerbations of chronic bronchitis: a single-blind, double-dummy, multicentre study. Author(s): Schouenborg P, Gerdes N, Rasmussen H, Wickers-Nielsen N, Mathiassen E. Source: J Int Med Res. 2000 May-June; 28(3): 101-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983860&dopt=Abstract
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Bacteriology and beta-lactamase activity in acute exacerbation of chronic bronchitis. Author(s): Brook I, Frazier EH. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2001; 5(2): 74-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468101&dopt=Abstract
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Beta2-agonists for acute bronchitis. Author(s): Smucny J, Flynn C, Becker L, Glazier R. Source: Cochrane Database Syst Rev. 2001; (1): Cd001726. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279725&dopt=Abstract
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Bronchial eosinophilia in exacerbation of bronchitis: an allergic profile of inflammation? Author(s): Costabel U. Source: American Journal of Respiratory and Critical Care Medicine. 2001 July 1; 164(1): 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435230&dopt=Abstract
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Bronchitis caused by Bordetella bronchiseptica in an elderly woman. Author(s): Petrocheilou-Paschou V, Georgilis K, Kostis E, Prifti H, Zakopoulos N, Stamatelopoulos S. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2000 March; 6(3): 147-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11168091&dopt=Abstract
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Bronchitis symptoms in young teenagers who actively or passively smoke cigarettes. Author(s): Manning P, Goodman P, Kinsella T, Lawlor M, Kirby B, Clancy L. Source: Ir Med J. 2002 July-August; 95(7): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227526&dopt=Abstract
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By the way, doctor. I recently had a hacking cough, and my doctor told me that I had bronchitis. He told me I didn't need antibiotics. is this some managed-care attempt to save money at my expense? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2000 November; 26(1): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063537&dopt=Abstract
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Can a patient information sheet reduce antibiotic use in adult outpatients with acute bronchitis? Author(s): DeBisschop M, Robitaille B. Source: The Journal of Family Practice. 2002 April; 51(4): 381. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978266&dopt=Abstract
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Cause of death in older patients with anatomo-pathological evidence of chronic bronchitis or emphysema: a case-control study based on autopsy findings. Author(s): Janssens JP, Herrmann F, MacGee W, Michel JP. Source: Journal of the American Geriatrics Society. 2001 May; 49(5): 571-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380749&dopt=Abstract
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Changes in bronchial inflammation during acute exacerbations of chronic bronchitis. Author(s): Gompertz S, O'Brien C, Bayley DL, Hill SL, Stockley RA. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 June; 17(6): 1112-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491152&dopt=Abstract
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Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment. Author(s): Blasi F, Damato S, Cosentini R, Tarsia P, Raccanelli R, Centanni S, Allegra L; Chlamydia InterAction with COPD (CIAC) Study Group. Source: Thorax. 2002 August; 57(8): 672-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149525&dopt=Abstract
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Chronic bronchitis among French adults: high prevalence and underdiagnosis. Author(s): Huchon GJ, Vergnenegre A, Neukirch F, Brami G, Roche N, Preux PM. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 October; 20(4): 806-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412668&dopt=Abstract
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Chronic bronchitis and emphysema: clearing the air. Author(s): Wisniewski A. Source: Nursing. 2003 May; 33(5): 46-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792571&dopt=Abstract
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Chronic cough due to latex-induced eosinophilic bronchitis. Author(s): Quirce S, Fernandez-Nieto M, de Miguel J, Sastre J. Source: The Journal of Allergy and Clinical Immunology. 2001 July; 108(1): 143. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11447398&dopt=Abstract
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Clinical efficacy of pneumococcal vaccination--a prospective study in patients with longstanding emphysema and/or bronchitis. Author(s): Franzen D. Source: European Journal of Medical Research. 2000 December 29; 5(12): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147998&dopt=Abstract
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Clinical features of eosinophilic bronchitis. Author(s): Joo JH, Park SJ, Park SW, Lee JH, Kim do J, Uh ST, Kim YH, Park CS. Source: Korean J Intern Med. 2002 March; 17(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014210&dopt=Abstract
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Clinical outcomes of ambulatory acute exacerbations of chronic bronchitis with older versus newer antimicrobials. Author(s): Madaras-Kelly KJ, Magdanz SB, Johnson CK, Jue SG. Source: The Annals of Pharmacotherapy. 2002 June; 36(6): 975-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022895&dopt=Abstract
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Comparative study of cefaclor AF vs. cefuroxime axetil in acute exacerbations of chronic bronchitis. Author(s): Haczynski J, Chyczewska E, Grzelewska-Rzymowska I, Malolepszy J, Marcinkowska-Suchowierska E, Milanowski J, Oklek K, Plusa T, Slominski J, Szmygin K, Rek M. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 January; 8(1): Pi1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782685&dopt=Abstract
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Comparative trial to evaluate the efficacy and tolerability of cefuroxime 250mg with probenecid 250mg with cefuroxime 500mg in the management of community acquired pneumonia, acute bronchitis and acute exacerbation of chronic bronchitis. Author(s): Rao PP, Mopkar O, Desai A. Source: J Indian Med Assoc. 2000 October; 98(10): 650-1, 654. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11258501&dopt=Abstract
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Comparison of 5-day, short-course gatifloxacin therapy with 7-day gatifloxacin therapy and 10-day clarithromycin therapy for acute exacerbation of chronic bronchitis. Author(s): Gotfried MH, DeAbate CA, Fogarty C, Mathew CP, Sokol WN. Source: Clinical Therapeutics. 2001 January; 23(1): 97-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219483&dopt=Abstract
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Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Author(s): Brightling CE, Symon FA, Birring SS, Bradding P, Wardlaw AJ, Pavord ID. Source: Thorax. 2003 June; 58(6): 528-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775868&dopt=Abstract
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Comparison of chest X-ray findings and other parameters in acute exacerbation of chronic bronchitis in Japan and the West. Author(s): Watanabe A, Kohno S, Niki Y, Saito A. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2001 March; 7(1): 37-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406755&dopt=Abstract
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Comparison of the efficacy of extended-release clarithromycin tablets and amoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis. Author(s): Anzueto A, Fisher CL Jr, Busman T, Olson CA. Source: Clinical Therapeutics. 2001 January; 23(1): 72-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219481&dopt=Abstract
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Costs of broad-spectrum antibiotic use for acute sinusitis, chronic bronchitis, and pneumonia in a managed care population. Author(s): Coughlin CM, Nelson M, Merchant S, Gondek K. Source: Manag Care Interface. 2003 June; 16(6): 34-40, 55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841074&dopt=Abstract
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Costs of chronic bronchitis and COPD: a 1-year follow-up study. Author(s): Miravitlles M, Murio C, Guerrero T, Gisbert R. Source: Chest. 2003 March; 123(3): 784-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628879&dopt=Abstract
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Cough syncope with herpetic tracheobronchitis. Author(s): Awad J, Schiller O. Source: Isr Med Assoc J. 2001 April; 3(4): 284-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344844&dopt=Abstract
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Diagnosis and management of acute bronchitis. Author(s): Knutson D, Braun C. Source: American Family Physician. 2002 May 15; 65(10): 2039-44. Review. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046770&dopt=Abstract
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Does drug treatment of patients with acute bronchitis reduce additional care seeking? Evidence from the Practice Partner Research Network. Author(s): Hueston WJ, Jenkins R, Mainous AG 3rd. Source: Archives of Family Medicine. 2000 November-December; 9(10): 997-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115198&dopt=Abstract
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Early determinants of first hospital admissions for asthma and acute bronchitis among Swedish children. Author(s): Braback L, Bjor O, Nordahl G. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003; 92(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650295&dopt=Abstract
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Effect of aerosolized uridine 5'-triphosphate on mucociliary clearance in mild chronic bronchitis. Author(s): Bennett WD, Zeman KL, Foy C, Shaffer CL, Johnson FL, Regnis JA, Sannuti A, Johnson J. Source: American Journal of Respiratory and Critical Care Medicine. 2001 July 15; 164(2): 302-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463605&dopt=Abstract
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Effect of sputum processing with dithiothreitol on the detection of inflammatory mediators in chronic bronchitis and bronchiectasis. Author(s): Woolhouse IS, Bayley DL, Stockley RA. Source: Thorax. 2002 August; 57(8): 667-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149524&dopt=Abstract
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Effect of sulfur dioxide and particulate pollutants on bronchitis in children--a risk analysis. Author(s): Herbarth O, Fritz G, Krumbiegel P, Diez U, Franck U, Richter M. Source: Environmental Toxicology. 2001 June; 16(3): 269-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409199&dopt=Abstract
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Effective use of corticosteroid in a child with life-threatening plastic bronchitis after Fontan operation. Author(s): Onoue Y, Adachi Y, Ichida F, Miyawaki T. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 February; 45(1): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654082&dopt=Abstract
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Effects of oral doxofylline on inflammatory changes and altered cell proliferation in chronic obstructive bronchitis. Author(s): Cogo R, Castronuovo A. Source: Eur Rev Med Pharmacol Sci. 2000 January-April; 4(1-2): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409184&dopt=Abstract
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Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial. Author(s): Matthys H, Eisebitt R, Seith B, Heger M. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 7-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807337&dopt=Abstract
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Efficacy and safety of azithromycin vs levofloxacin in the outpatient treatment of acute bacterial exacerbations of chronic bronchitis. Author(s): Amsden GW, Baird IM, Simon S, Treadway G. Source: Chest. 2003 March; 123(3): 772-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628877&dopt=Abstract
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Efficacy and safety of short course (5-day) moxifloxacin vs 7-day ceftriaxone in the treatment of acute exacerbations of chronic bronchitis (AECB). Author(s): Grassi C, Casali L, Curti E, Tellarini M, Lazzaro C, Schito G; SMART Study Group. Studio Multicentrico con Moxifloxacina nel Trattamento delle Riacutizzazioni de Bronchite Cronica. Source: Journal of Chemotherapy (Florence, Italy). 2002 December; 14(6): 597-608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583552&dopt=Abstract
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Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis. Author(s): Anzueto A, Gotfried M, Wikler MA, Russo R, Nicholson SC. Source: Clinical Therapeutics. 2002 June; 24(6): 906-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117081&dopt=Abstract
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Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol. Author(s): Matthys H, de Mey C, Carls C, Rys A, Geib A, Wittig T. Source: Arzneimittel-Forschung. 2000 August; 50(8): 700-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994153&dopt=Abstract
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Efficacy of gemifloxacin in acute exacerbations of chronic bronchitis: a randomised, double-blind comparison with trovafloxacin. Author(s): Ball P, Wilson R, Mandell L, Brown J, Henkel T; 069 Clinical Study Group. Source: Journal of Chemotherapy (Florence, Italy). 2001 June; 13(3): 288-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450888&dopt=Abstract
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Eosinophilic bronchitis as a cause of chronic cough. Author(s): Ayik SO, Basoglu OK, Erdinc M, Bor S, Veral A, Bilgen C. Source: Respiratory Medicine. 2003 June; 97(6): 695-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814157&dopt=Abstract
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Eosinophilic bronchitis. Author(s): Hancox RJ, Leigh R, Kelly MM, Hargreave FE. Source: Lancet. 2001 September 29; 358(9287): 1104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600996&dopt=Abstract
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Eosinophilic bronchitis: an important cause of prolonged cough. Author(s): Brightling CE, Pavord ID. Source: Annals of Medicine. 2000 October; 32(7): 446-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11087164&dopt=Abstract
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Eosinophilic bronchitis: clinical manifestations and implications for treatment. Author(s): Gibson PG, Fujimura M, Niimi A. Source: Thorax. 2002 February; 57(2): 178-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828051&dopt=Abstract
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Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis. Author(s): Bocchino V, Bertorelli G, Bertrand CP, Ponath PD, Newman W, Franco C, Marruchella A, Merlini S, Del Donno M, Zhuo X, Olivieri D. Source: Allergy. 2002 January; 57(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991282&dopt=Abstract
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Equal effectiveness of older traditional antibiotics and newer broad-spectrum antibiotics in treating patients with acute exacerbations of chronic bronchitis. Author(s): Peng CC, Aspinall SL, Good CB, Atwood CW Jr, Chang CC. Source: Southern Medical Journal. 2003 October; 96(10): 986-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570342&dopt=Abstract
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Esberitox N as supportive therapy when providing standard antibiotic treatment in subjects with a severe bacterial infection (acute exacerbation of chronic bronchitis). A multicentric, prospective, double-blind, placebo-controlled study. Author(s): Hauke W, Kohler G, Henneicke-Von Zepelin HH, Freudenstein J. Source: Chemotherapy. 2002 December; 48(5): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476043&dopt=Abstract
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Evaluation and treatment of acute bronchitis at an academic teaching clinic. Author(s): Hall KK, Philbrick J, Nadkarni M. Source: The American Journal of the Medical Sciences. 2003 January; 325(1): 7-9. Erratum In: Am J Med Sci. 2003 May; 325(5): 303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544078&dopt=Abstract
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Evidence of bacterial infection in acute exacerbations of chronic bronchitis. Author(s): Wilson R. Source: Seminars in Respiratory Infections. 2000 September; 15(3): 208-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052421&dopt=Abstract
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Evidence-based emergency medicine. Antibiotic treatment for acute bronchitis. Author(s): Edmonds ML. Source: Annals of Emergency Medicine. 2002 July; 40(1): 110-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085081&dopt=Abstract
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Exacerbations of Bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants. Author(s): Zhu J, Qiu YS, Majumdar S, Gamble E, Matin D, Turato G, Fabbri LM, Barnes N, Saetta M, Jeffery PK. Source: American Journal of Respiratory and Critical Care Medicine. 2001 July 1; 164(1): 109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435248&dopt=Abstract
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Exposure to cold and draught, alcohol consumption, and the NS-phenotype are associated with chronic bronchitis: an epidemiological investigation of 3387 men aged 53-75 years: the Copenhagen Male Study. Author(s): Suadicani P, Hein HO, Meyer HW, Gyntelberg F. Source: Occupational and Environmental Medicine. 2001 March; 58(3): 160-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171928&dopt=Abstract
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Exposures to the Kuwait oil fires and their association with asthma and bronchitis among gulf war veterans. Author(s): Lange JL, Schwartz DA, Doebbeling BN, Heller JM, Thorne PS. Source: Environmental Health Perspectives. 2002 November; 110(11): 1141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417486&dopt=Abstract
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FAB-MS characterization of sialyl Lewis x determinants on polylactosamine chains of human airway mucins secreted by patients suffering from cystic fibrosis or chronic bronchitis. Author(s): Morelle W, Sutton-Smith M, Morris HR, Davril M, Roussel P, Dell A. Source: Glycoconjugate Journal. 2001 September; 18(9): 699-708. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386455&dopt=Abstract
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Factors associated with relapse after ambulatory treatment of acute exacerbations of chronic bronchitis. DAFNE Study Group. Author(s): Miravitlles M, Murio C, Guerrero T. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 May; 17(5): 928-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488328&dopt=Abstract
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Familial related risk-factors in the development of chronic bronchitis/emphysema as compared to asthma assessed in a postal survey. Author(s): Montnemery P, Lanke J, Lindholm LH, Lundback B, Nyberg P, Adelroth E, Lofdahl CG. Source: European Journal of Epidemiology. 2000; 16(11): 1003-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421467&dopt=Abstract
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Five days of cefprozil versus 10 days of clarithromycin in the treatment of an acute exacerbation of chronic bronchitis. Author(s): McCarty JM, Pierce PF. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2001 October; 87(4): 327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11686426&dopt=Abstract
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Foreign-body aspiration, asthma and chronic bronchitis. Author(s): Deshpande KS, Haramati LB, Aldrich TK, Edelman M, Villanueva E. Source: American Family Physician. 2000 October 1; 62(7): 1513, 1517, 1519. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037072&dopt=Abstract
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Formulary decision making and acute exacerbations of chronic bronchitis. Author(s): Penna P. Source: Manag Care Interface. 2001 February; 14(2): 50-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228816&dopt=Abstract
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Gene expression and immunolocalization of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis. Author(s): Zhu J, Kilty I, Granger H, Gamble E, Qiu YS, Hattotuwa K, Elston W, Liu WL, Oliva A, Pauwels RA, Kips JC, De Rose V, Barnes N, Yeadon M, Jenkinson S, Jeffery PK. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 December; 27(6): 666-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444026&dopt=Abstract
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Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes. Author(s): Silverman EK, Mosley JD, Palmer LJ, Barth M, Senter JM, Brown A, Drazen JM, Kwiatkowski DJ, Chapman HA, Campbell EJ, Province MA, Rao DC, Reilly JJ, Ginns LC, Speizer FE, Weiss ST. Source: Human Molecular Genetics. 2002 March 15; 11(6): 623-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912177&dopt=Abstract
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Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis. Author(s): Foxwell AR, Cripps AW, Dear KB. Source: Cochrane Database Syst Rev. 2003; (3): Cd001958. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917917&dopt=Abstract
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Healthy worker effect in cohort studies on chronic bronchitis. Author(s): Radon K, Goldberg M, Becklake M. Source: Scand J Work Environ Health. 2002 October; 28(5): 328-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432986&dopt=Abstract
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Heat shock proteins mRNA expressions by peripheral blood mononuclear cells in asthma and chronic bronchitis. Author(s): Tong W, Luo W. Source: Chinese Medical Journal. 2000 February; 113(2): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775547&dopt=Abstract
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Helicobacter pylori seroprevalence in patients with chronic bronchitis. Author(s): Roussos A, Tsimpoukas F, Anastasakou E, Alepopoulou D, Paizis I, Philippou N. Source: Journal of Gastroenterology. 2002; 37(5): 332-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051531&dopt=Abstract
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How accurate is the self-reported diagnosis of chronic bronchitis? Author(s): Bobadilla A, Guerra S, Sherrill D, Barbee R. Source: Chest. 2002 October; 122(4): 1234-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377847&dopt=Abstract
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Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 September; 113(9): 1241-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959742&dopt=Abstract
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IgG subclasses in smokers with chronic bronchitis and recurrent exacerbations. Author(s): Qvarfordt I, Riise GC, Andersson BA, Larsson S. Source: Thorax. 2001 June; 56(6): 445-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359959&dopt=Abstract
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Immune response to Fusobacterium nucleatum and Prevotella intermedia in the sputum of patients with acute exacerbation of chronic bronchitis. Author(s): Brook I, Frazier EH. Source: Chest. 2003 September; 124(3): 832-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970005&dopt=Abstract
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Impact of reducing antibiotic prescribing for acute bronchitis on patient satisfaction. Author(s): Gonzales R, Steiner JF, Maselli J, Lum A, Barrett PH Jr. Source: Effective Clinical Practice : Ecp. 2001 May-June; 4(3): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434073&dopt=Abstract
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Improved sputum expectoration following a single dose of INS316 in patients with chronic bronchitis. Author(s): Johnson FL, Donohue JF, Shaffer CL. Source: Chest. 2002 December; 122(6): 2021-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475842&dopt=Abstract
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Improving quality or shifting diagnoses? What happens when antibiotic prescribing is reduced for acute bronchitis? Author(s): Hueston WJ, Slott K. Source: Archives of Family Medicine. 2000 September-October; 9(9): 933-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031404&dopt=Abstract
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In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. Author(s): Loppow D, Schleiss MB, Kanniess F, Taube C, Jorres RA, Magnussen H. Source: Respiratory Medicine. 2001 February; 95(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217907&dopt=Abstract
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Index of suspicion. Case 1. Diagnosis: Recurrent or persistent rhinitis and bronchitis. Author(s): Kaditis AG, Gourgoulianis K, Liatsis M. Source: Pediatrics in Review / American Academy of Pediatrics. 2001 August; 22(8): 271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483853&dopt=Abstract
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Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma. Author(s): Brightling CE, Ward R, Woltmann G, Bradding P, Sheller JR, Dworski R, Pavord ID. Source: American Journal of Respiratory and Critical Care Medicine. 2000 September; 162(3 Pt 1): 878-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10988099&dopt=Abstract
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Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles. Author(s): Corse E, Machamer CE. Source: Journal of Virology. 2000 May; 74(9): 4319-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10756047&dopt=Abstract
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Inflammation and acute exacerbations of chronic bronchitis. Author(s): Stockley RA. Source: Chest. 2001 October; 120(4): 1422-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591596&dopt=Abstract
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Interleukin-4 and interleukin-5 gene expression and inflammation in the mucussecreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells. Author(s): Zhu J, Majumdar S, Qiu Y, Ansari T, Oliva A, Kips JC, Pauwels RA, De Rose V, Jeffery PK. Source: American Journal of Respiratory and Critical Care Medicine. 2001 December 15; 164(12): 2220-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751191&dopt=Abstract
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Leisure time physical activity and disease-specific mortality among men with chronic bronchitis: evidence from the Whitehall study. Author(s): Batty GD, Shipley MJ, Marmot MG, Smith GD. Source: American Journal of Public Health. 2003 May; 93(5): 817-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721150&dopt=Abstract
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Linking Helicobacter pylori and chronic bronchitis: fact or fancy? Author(s): Shiotani A. Source: Journal of Gastroenterology. 2002; 37(5): 402-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051543&dopt=Abstract
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Lipid peroxidation--antioxidant activity system in erythrocytes of patients with chronic bronchitis inhaling and not inhaling ozone. Author(s): Abdrashitova NF, Romanov YA. Source: Bulletin of Experimental Biology and Medicine. 2001 September; 132(3): 884-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740585&dopt=Abstract
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Localised obliterative bronchitis due to non-occupational mineral dust inhalation. Author(s): Meysman M, Monsieur I, Noppen M, Vincken W. Source: Acta Clin Belg. 2000 November-December; 55(6): 341-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484425&dopt=Abstract
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Longitudinal study of childhood wheezy bronchitis and asthma: outcome at age 42. Author(s): Horak E, Lanigan A, Roberts M, Welsh L, Wilson J, Carlin JB, Olinsky A, Robertson CF. Source: Bmj (Clinical Research Ed.). 2003 February 22; 326(7386): 422-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595380&dopt=Abstract
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Long-term treatment of angina pectoris with bisoprolol or atenolol in patients with chronic obstructive bronchitis: a randomized, double-blind crossover study. Author(s): Dorow P, Thalhofer S, Bethge H, Disselhoff G, Wagner G. Source: Journal of Cardiovascular Pharmacology. 1990; 16 Suppl 5: S36-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527135&dopt=Abstract
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Lower airway bacterial colonization in asymptomatic smokers and smokers with chronic bronchitis and recurrent exacerbations. Author(s): Qvarfordt I, Riise GC, Andersson BA, Larsson S. Source: Respiratory Medicine. 2000 September; 94(9): 881-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001080&dopt=Abstract
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Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. Author(s): Jeffery PK. Source: Novartis Found Symp. 2001; 234: 149-61; Discussion 161-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199094&dopt=Abstract
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Managing patients with chronic bronchitis: from primary prevention to advance directives. Author(s): Schaberg DR. Source: Hosp Pract (Off Ed). 2000 November 15; 35(11): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108002&dopt=Abstract
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Moxifloxacin in acute exacerbations of chronic bronchitis: clinical evaluation and assessment by patients. Author(s): Lorenz J, Busch W, Thate-Waschke IM; BRONCHIMOX Study Group. Source: J Int Med Res. 2001 March-April; 29(2): 61-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393350&dopt=Abstract
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Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Author(s): Poole PJ, Black PN. Source: Cochrane Database Syst Rev. 2003; (2): Cd001287. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804402&dopt=Abstract
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Necrotizing tracheobronchitis in patent ductus arteriosus-dependent cyanotic congenital heart disease. Author(s): Nakata Y, Morikawa Y, Miura M, Kawasaki K, Toyoma H, Kameyama K. Source: Pediatric Pulmonology. 2001 December; 32(6): 480-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747253&dopt=Abstract
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Nodular invasive tracheobronchitis due to Aspergillus in a patient with systemic lupus erythematosus. Author(s): Angelotti T, Krishna G, Scott J, Berry G, Weinacker A. Source: Lupus. 2002; 11(5): 325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090570&dopt=Abstract
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Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis. Author(s): Bandi V, Apicella MA, Mason E, Murphy TF, Siddiqi A, Atmar RL, Greenberg SB. Source: American Journal of Respiratory and Critical Care Medicine. 2001 December 1; 164(11): 2114-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739144&dopt=Abstract
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Nosocomial tracheobronchitis in mechanically ventilated patients: incidence, aetiology and outcome. Author(s): Nseir S, Di Pompeo C, Pronnier P, Beague S, Onimus T, Saulnier F, Grandbastien B, Mathieu D, Delvallez-Roussel M, Durocher A. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 December; 20(6): 1483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503708&dopt=Abstract
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Novel mechanistic targets for the treatment of sub-acute and chronic bronchitis. Author(s): Wegner CD. Source: Current Pharmaceutical Design. 2001 February; 7(3): 199-212. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11311113&dopt=Abstract
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Obstructive sleep apnoea syndrome is common in subjects with chronic bronchitis. Report from the Obstructive Lung Disease in Northern Sweden studies. Author(s): Larsson LG, Lindberg A, Franklin KA, Lundback B; Obstructive Lung Disease in Northern Sweden Studies. Source: Respiration; International Review of Thoracic Diseases. 2001; 68(3): 250-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11416244&dopt=Abstract
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Occupation, chronic bronchitis, and lung function in young adults. An international study. Author(s): Zock JP, Sunyer J, Kogevinas M, Kromhout H, Burney P, Anto JM. Source: American Journal of Respiratory and Critical Care Medicine. 2001 June; 163(7): 1572-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401876&dopt=Abstract
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Open-label, randomized comparison of the efficacy and tolerability of clarithromycin, levofloxacin, and cefuroxime axetil in the treatment of adults with acute bacterial exacerbations of chronic bronchitis. Author(s): Weiss LR. Source: Clinical Therapeutics. 2002 September; 24(9): 1414-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380633&dopt=Abstract
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Optimal treatment strategies for acute exacerbations of chronic bronchitis: high-risk patients. Author(s): Norrby SR. Source: Chemotherapy. 2001; 47 Suppl 4: 47-52; Discussion 53-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586005&dopt=Abstract
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Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis. Author(s): Lubasch A, Luck S, Lode H, Mauch H, Lorenz J, Bolcskei P, Welte T; COPD Study Group. Source: The Journal of Antimicrobial Chemotherapy. 2003 March; 51(3): 659-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615868&dopt=Abstract
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Optimizing economic outcomes in acute exacerbations of chronic bronchitis. Author(s): Destache CJ. Source: Pharmacotherapy. 2002 January; 22(1 Pt 2): 12S-17S; Discussion 30S-32S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791624&dopt=Abstract
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Oral gemifloxacin once daily for 5 days compared with sequential therapy with i.v. ceftriaxone/oral cefuroxime (maximum of 10 days) in the treatment of hospitalized patients with acute exacerbations of chronic bronchitis. Author(s): Wilson R, Langan C, Ball P, Bateman K, Pypstra R; Gemifloxacin 207 Clinical Study Group. Source: Respiratory Medicine. 2003 March; 97(3): 242-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645831&dopt=Abstract
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Passive smoking exposure: a risk factor for chronic bronchitis and asthma in adults? Author(s): Radon K, Busching K, Heinrich J, Wichmann HE, Jorres RA, Magnussen H, Nowak D. Source: Chest. 2002 September; 122(3): 1086-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226059&dopt=Abstract
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Patient and physician explanatory models for acute bronchitis. Author(s): Snell LM, Wilson RP, Oeffinger KC, Sargent C, Chen O, Corey KM. Source: The Journal of Family Practice. 2002 December; 51(12): 1035-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540329&dopt=Abstract
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Persistent adenoviral infection and chronic obstructive bronchitis in children: is there a link? Author(s): Pichler M, Herrmann G, Schmidt H, Ahrens P, Zielen S. Source: Pediatric Pulmonology. 2001 November; 32(5): 367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11596161&dopt=Abstract
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Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Author(s): Miravitlles M, Murio C, Guerrero T, Gisbert R; DAFNE Study Group. Decisiones sobre Antibioticoterapia y Farmacoeconomia en la EPOC. Source: Chest. 2002 May; 121(5): 1449-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006427&dopt=Abstract
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Pharmacokinetic/pharmacodynamic predictors of time to clinical resolution in patients with acute bacterial exacerbations of chronic bronchitis treated with a fluoroquinolone. Author(s): Meinl B, Hyatt JM, Forrest A, Chodosh S, Schentag JJ. Source: International Journal of Antimicrobial Agents. 2000 November; 16(3): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11091047&dopt=Abstract
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Pharmacy-based intervention to reduce antibiotic use for acute bronchitis. Author(s): Hickman DE, Stebbins MR, Hanak JR, Guglielmo BJ. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549944&dopt=Abstract
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Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis. Author(s): Adler JL, Jannetti W, Schneider D, Zhang J, Palmer R, Notario G. Source: Clinical Therapeutics. 2000 December; 22(12): 1410-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192133&dopt=Abstract
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Plastic bronchitis and the role of bronchoscopy in the acute chest syndrome of sickle cell disease. Author(s): Moser C, Nussbaum E, Cooper DM. Source: Chest. 2001 August; 120(2): 608-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502666&dopt=Abstract
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Plastic bronchitis in children with Fontan palliation: analogue to protein losing enteropathy? Author(s): Stiller B, Riedel F, Paul K, van Landeghem FK. Source: Pediatric Cardiology. 2002 January-February; 23(1): 90-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924535&dopt=Abstract
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Plastic bronchitis in children: a case series and review of the medical literature. Author(s): Brogan TV, Finn LS, Pyskaty DJ Jr, Redding GJ, Ricker D, Inglis A, Gibson RL. Source: Pediatric Pulmonology. 2002 December; 34(6): 482-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422347&dopt=Abstract
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Plastic bronchitis mimicking foreign body aspiration that needs a specific diagnostic procedure. Author(s): Noizet O, Leclerc F, Leteurtre S, Brichet A, Pouessel G, Dorkenoo A, Fourier C, Cremer R. Source: Intensive Care Medicine. 2003 February; 29(2): 329-31. Epub 2003 January 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594596&dopt=Abstract
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Plastic bronchitis: an unusual bronchoscopic challenge associated with congenital heart disease repair. Author(s): Ishman S, Book DT, Conley SF, Kerschner JE. Source: International Journal of Pediatric Otorhinolaryngology. 2003 May; 67(5): 543-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697358&dopt=Abstract
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Pre-protachykinin-A mRNA is increased in the airway epithelium of smokers with chronic bronchitis. Author(s): Reynolds PN, Scicchitano R, Holmes MD. Source: Respirology (Carlton, Vic.). 2001 September; 6(3): 187-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555376&dopt=Abstract
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Prevalence and risk factors for asthma and chronic bronchitis in the capitals Helsinki, Stockholm, and Tallinn. Author(s): Pallasaho P, Lundback B, Meren M, Kiviloog J, Loit HM, Larsson K, Laitinen LA. Source: Respiratory Medicine. 2002 October; 96(10): 759-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412974&dopt=Abstract
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Prevalence of chronic bronchitis and chronic respiratory symptoms in adults over the age of 35 years in Isfahan, Iran in 1998. Author(s): Golshan M, Barahimi H, Nasirian K. Source: Respirology (Carlton, Vic.). 2001 September; 6(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555382&dopt=Abstract
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Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema. Author(s): Bousquet J, Leynaert B, Neukirch F. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 January; 19(1): 202-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843322&dopt=Abstract
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Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema. Author(s): Montnemery P, Svensson C, Adelroth E, Lofdahl CG, Andersson M, Greiff L, Persson CG. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 April; 17(4): 596-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401051&dopt=Abstract
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Preventing exacerbations of chronic bronchitis and COPD. Author(s): Ekberg-Jansson A, Larsson S, Lofdahl CG. Source: Bmj (Clinical Research Ed.). 2001 May 26; 322(7297): 1259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375214&dopt=Abstract
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Prevention with clodronate of osteoporosis secondary to inhaled corticosteroid treatment in patients with chronic asthmatic bronchitis. Author(s): Muratore M, Santacesaria G, Quarta E, Calcagnile F, Cosentino L, Muratore L. Source: Int J Clin Pharmacol Res. 2000; 20(3-4): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314239&dopt=Abstract
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Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Author(s): Snow V, Mottur-Pilson C, Gonzales R; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine; Centers for Disease Control; Infectious Diseases Society of America. Source: Annals of Internal Medicine. 2001 March 20; 134(6): 518-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255531&dopt=Abstract
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Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Author(s): Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JM, Hoffman JR, Sande MA; Centers for Disease Control and Prevention. Source: Annals of Emergency Medicine. 2001 June; 37(6): 720-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385346&dopt=Abstract
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Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Author(s): Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JM, Hoffman JR, Sande MA; American Academy of Family Physicians; American College of PhysiciansAmerican Society of Internal Medicine; Centers for Disease Control; Infectious Diseases Society of America. Source: Annals of Internal Medicine. 2001 March 20; 134(6): 521-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255532&dopt=Abstract
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Principles of appropriate antibiotic use: part V. Acute bronchitis. Author(s): Ressel G; Centers for Disease Control and Prevention; American College of Physicians--American Society of Internal Medicine; American Academy of Family Physicians; Infectious Diseases Society of America. Source: American Family Physician. 2001 September 15; 64(6): 1098, 1100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578027&dopt=Abstract
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Prophylactic antibiotic therapy for chronic bronchitis. Author(s): Black P, Staykova T, Chacko E, Ram FS, Poole P. Source: Cochrane Database Syst Rev. 2003; (1): Cd004105. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535510&dopt=Abstract
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Pseudomembranous aspergillus bronchitis in a double-lung transplanted patient: unusual radiographic and CT features. Author(s): Ducreux D, Chevallier P, Perrin C, Jourdan J, Hofman P, Raffaelli C, Padovani B. Source: European Radiology. 2000; 10(10): 1547-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044922&dopt=Abstract
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Pseudomembranous tracheobronchitis caused by Aspergillus in a patient after peripheral blood stem cell transplantation. Author(s): Koh LP, Goh YT, Linn YC, Hwang J, Tan P. Source: Ann Acad Med Singapore. 2000 July; 29(4): 531-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056787&dopt=Abstract
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Pseudomembranous tracheobronchitis caused by methicillin-resistant Staphylococcus aureus. Author(s): Yamazaki Y, Hirai K, Honda T. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(3): 211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030399&dopt=Abstract
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Pseudomembranous tracheobronchitis due to Bacillus cereus. Author(s): Strauss R, Mueller A, Wehler M, Neureiter D, Fischer E, Gramatzki M, Hahn EG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 September 1; 33(5): E39-41. Epub 2001 August 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486300&dopt=Abstract
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Public knowledge, attitudes, and experiences with antibiotic use for acute bronchitis. Author(s): Teramoto S, Matsuse T, Fukuchi Y. Source: The American Journal of Medicine. 2001 February 15; 110(3): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221640&dopt=Abstract
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Quality of life in acute exacerbation of chronic bronchitis: results from a German population study. Author(s): Doll H, Grey-Amante P, Duprat-Lomon I, Sagnier PP, Thate-Waschke I, Lorenz J, Rychlik R, Pfeil T. Source: Respiratory Medicine. 2002 January; 96(1): 39-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863209&dopt=Abstract
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Quantification of the effect of inhaled budesonide on airway inflammation in intermittent asthma by bronchitis index. Author(s): John M, Fietze I, Borges AC, Oltmanns U, Schmidt B, Witt C. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 2001 October; 38(7): 593-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714082&dopt=Abstract
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Randomised double-blind comparison of oral gatifloxacin and co-amoxiclav for acute exacerbation of chronic Bronchitis. Author(s): Soler M, Lode H, Baldwin R, Levine JH, Schreurs AJ, van Noord JA, Maesen FP, Zehrer M; European Gatifloxacin Study group. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 March; 22(3): 144-50. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649711&dopt=Abstract
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Randomized, double-blind study comparing 5- and 7-day regimens of oral levofloxacin in patients with acute exacerbation of chronic bronchitis. Author(s): Masterton RG, Burley CJ. Source: International Journal of Antimicrobial Agents. 2001 December; 18(6): 503-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738336&dopt=Abstract
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Randomized, double-blind study of prulifloxacin versus ciprofloxacin in patients with acute exacerbations of chronic bronchitis. Author(s): Grassi C, Salvatori E, Rosignoli MT, Dionisio P; Prulifloxacin Study Group. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(3): 217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097764&dopt=Abstract
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Randomized, double-blind, double-dummy study comparing the efficacy and safety of amoxycillin 1 g bd with amoxycillin 500 mg tds in the treatment of acute exacerbations of chronic bronchitis. Author(s): Georgopoulos A, Borek M, Ridl W; Amoxycillin Bronchitis Study Group. Source: The Journal of Antimicrobial Chemotherapy. 2001 January; 47(1): 67-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152433&dopt=Abstract
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Recent advances in diagnosis and management of chronic bronchitis and emphysema. Author(s): Chitkara RK, Sarinas PS. Source: Current Opinion in Pulmonary Medicine. 2002 March; 8(2): 126-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845008&dopt=Abstract
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Redecoration of apartments promotes obstructive bronchitis in atopy risk infants-results of the LARS Study. Author(s): Diez U, Rehwagen M, Rolle-Kampczyk U, Wetzig H, Schulz R, Richter M, Lehmann I, Borte M, Herbarth O. Source: International Journal of Hygiene and Environmental Health. 2003 June; 206(3): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872525&dopt=Abstract
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Reducing antibiotic use for acute bronchitis by giving patients written information. Author(s): Farquhar D. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 March 19; 166(6): 776. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944766&dopt=Abstract
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Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet. Author(s): Macfarlane J, Holmes W, Gard P, Thornhill D, Macfarlane R, Hubbard R. Source: Bmj (Clinical Research Ed.). 2002 January 12; 324(7329): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786454&dopt=Abstract
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Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis. Author(s): White AJ, Gompertz S, Bayley DL, Hill SL, O'Brien C, Unsal I, Stockley RA. Source: Thorax. 2003 August; 58(8): 680-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885984&dopt=Abstract
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Respiratory infection in the chronically critically ill patient. Ventilator-associated pneumonia and tracheobronchitis. Author(s): Ahmed QA, Niederman MS. Source: Clinics in Chest Medicine. 2001 March; 22(1): 71-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315460&dopt=Abstract
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Respiratory symptoms, bronchitis and asthma in children of Central and Eastern Europe. Author(s): Leonardi GS, Houthuijs D, Nikiforov B, Volf J, Rudnai P, Zejda J, Gurzau E, Fabianova E, Fletcher T, Brunekreef B. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 October; 20(4): 890-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412680&dopt=Abstract
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Rethinking doctrine: bronchitis, eosinophils, and bronchoscopy in pediatric asthma. Author(s): Gaston B. Source: The Journal of Allergy and Clinical Immunology. 2002 July; 110(1): 24-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110812&dopt=Abstract
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Safety and effectiveness of lomefloxacin in patients with acute exacerbation of chronic bronchitis (AECB) chronically treated with oral theophyllines. Author(s): Melani AS, Pirrelli M, Sarlo F, Cantoni V; Lo-Theo Study Group. Source: Journal of Chemotherapy (Florence, Italy). 2001 December; 13(6): 628-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806624&dopt=Abstract
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Sauropus androgynus-constrictive obliterative bronchitis/bronchiolitis-histopathological study of pneumonectomy and biopsy specimens with emphasis on the inflammatory process and disease progression. Author(s): Wang JS, Tseng HH, Lai RS, Hsu HK, Ger LP. Source: Histopathology. 2000 November; 37(5): 402-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119121&dopt=Abstract
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Selection of clinical, patient-reported, and economic end points in acute exacerbation of chronic bronchitis. Author(s): Perfetto EM, Mullins CD, Subedi P, Li-McLeod J. Source: Clinical Therapeutics. 2001 October; 23(10): 1747-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726009&dopt=Abstract
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Serum levels of mannan-binding lectin in chickens prior to and during experimental infection with avian infectious bronchitis virus. Author(s): Juul-Madsen HR, Munch M, Handberg KJ, Sorensen P, Johnson AA, Norup LR, Jorgensen PH. Source: Poultry Science. 2003 February; 82(2): 235-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619800&dopt=Abstract
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Should patients with acute cough or bronchitis be treated with beta-2 agonists? Author(s): Marsland TW, Newton WP. Source: The Journal of Family Practice. 2002 February; 51(2): 170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978217&dopt=Abstract
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Should we prescribe antibiotics for acute bronchitis? Author(s): Chandran R. Source: American Family Physician. 2001 July 1; 64(1): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456430&dopt=Abstract
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Solutions for difficult diagnostic cases of acute exacerbations of chronic bronchitis. Author(s): Tsang KW. Source: Chemotherapy. 2001; 47 Suppl 4: 28-38; Discussion 53-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586003&dopt=Abstract
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Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers. Author(s): Hauser R, Eisen EA, Pothier L, Lewis D, Bledsoe T, Christiani DC. Source: Chest. 2002 June; 121(6): 2052-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065377&dopt=Abstract
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Symptom resolution assessed using a patient directed diary card during treatment of acute exacerbations of chronic bronchitis. Author(s): Woolhouse IS, Hill SL, Stockley RA. Source: Thorax. 2001 December; 56(12): 947-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713358&dopt=Abstract
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Symptoms related to obstructive sleep apnoea are common in subjects with asthma, chronic bronchitis and rhinitis in a general population. Author(s): Larsson LG, Lindberg A, Franklin KA, Lundback B. Source: Respiratory Medicine. 2001 May; 95(5): 423-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392586&dopt=Abstract
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Telithromycin is as effective as amoxicillin/clavulanate in acute exacerbations of chronic bronchitis. Author(s): Aubier M, Aldons PM, Leak A, McKeith DD, Leroy B, Rangaraju M, BienfaitBeuzon C. Source: Respiratory Medicine. 2002 November; 96(11): 862-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418583&dopt=Abstract
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TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. Author(s): Brightling CE, Symon FA, Birring SS, Bradding P, Pavord ID, Wardlaw AJ. Source: The Journal of Allergy and Clinical Immunology. 2002 December; 110(6): 899905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464957&dopt=Abstract
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The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design. BRONCUS-trial Committee. Author(s): Cochrane Database Syst Rev. 2002;(1):CD002996 Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 March; 17(3): 329-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11869647
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The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency. Author(s): Am Fam Physician. 2002 May 15;65(10):2046 Source: American Journal of Respiratory and Critical Care Medicine. 2002 June 1; 165(11): 1494-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046771
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The efficacy of moxifloxacin in acute exacerbations of chronic bronchitis: a Spanish physician and patient experience. Author(s): Miravitlles M, Ros F, Cobos A, Kubin R, Tillotson G. Source: Int J Clin Pract. 2001 September; 55(7): 437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594251&dopt=Abstract
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The excess cost of acute exacerbations of chronic bronchitis in patients aged 45 and older in England and Wales. Author(s): McGuire A, Irwin DE, Fenn P, Gray A, Anderson P, Lovering A, MacGowan A. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2001 September-October; 4(5): 370-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705127&dopt=Abstract
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The importance of appropriate treatment of chronic bronchitis. Author(s): Anzueto A. Source: Am J Manag Care. 2000 May; 6(8 Suppl): S437-41. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10977483&dopt=Abstract
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The place of antibiotic therapy in the management of chronic acute exacerbations of chronic bronchitis. Author(s): Akalin HE. Source: International Journal of Antimicrobial Agents. 2001; 18 Suppl 1: S49-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574196&dopt=Abstract
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The relation of body mass index to asthma, chronic bronchitis, and emphysema. Author(s): Guerra S, Sherrill DL, Bobadilla A, Martinez FD, Barbee RA. Source: Chest. 2002 October; 122(4): 1256-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377850&dopt=Abstract
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The safety and efficacy of short course (5-day) moxifloxacin vs. azithromycin in the treatment of patients with acute exacerbation of chronic bronchitis. Author(s): DeAbate CA, Mathew CP, Warner JH, Heyd A, Church D. Source: Respiratory Medicine. 2000 November; 94(11): 1029-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127487&dopt=Abstract
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The spectrum of acute bronchitis. Using baseline factors to guide empirical therapy. Author(s): Flaherty KR, Saint S, Fendrick AM, Martinez FJ. Source: Postgraduate Medicine. 2001 February; 109(2): 39-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272693&dopt=Abstract
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The treatment of acute bronchitis by general practitioners in the UK. Results of a cross sectional postal survey. Author(s): Stocks NP, Fahey T. Source: Aust Fam Physician. 2002 July; 31(7): 676-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143330&dopt=Abstract
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Thromboxane antagonism and cough in chronic bronchitis. Author(s): Ishiura Y, Fujimura M, Yamamori C, Nobata K, Myou S, Kurashima K, Takegoshi T. Source: Annals of Medicine. 2003; 35(2): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795341&dopt=Abstract
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Time course of recovery of health status following an infective exacerbation of chronic bronchitis. Author(s): Spencer S, Jones PW; GLOBE Study Group. Source: Thorax. 2003 July; 58(7): 589-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832673&dopt=Abstract
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Tracheobronchitis as an initial presentation of ulcerative colitis. Author(s): Shad JA, Sharieff GQ. Source: Journal of Clinical Gastroenterology. 2001 August; 33(2): 161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468448&dopt=Abstract
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Treating acute exacerbations of chronic bronchitis in the face of antibiotic resistance. Author(s): Adams SG, Anzueto A. Source: Cleve Clin J Med. 2000 September; 67(9): 625-8, 631-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992620&dopt=Abstract
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Treating acute exacerbations of chronic bronchitis. Author(s): San Pedro G, George R. Source: Hosp Pract (Off Ed). 2000 November 15; 35(11): 43-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108005&dopt=Abstract
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Treatment of cast bronchitis with low-dose oral azithromycin. Author(s): Schultz KD, Oermann CM. Source: Pediatric Pulmonology. 2003 February; 35(2): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526076&dopt=Abstract
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Treatment of plastic bronchitis in a Fontan patient with tissue plasminogen activator: a case report and review of the literature. Author(s): Costello JM, Steinhorn D, McColley S, Gerber ME, Kumar SP. Source: Pediatrics. 2002 April; 109(4): E67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927740&dopt=Abstract
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Treatment of plastic bronchitis in acute chest syndrome of sickle cell disease with intratracheal rhDNase. Author(s): Manna SS, Shaw J, Tibby SM, Durward A. Source: Archives of Disease in Childhood. 2003 July; 88(7): 626-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818912&dopt=Abstract
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Treatment outcomes in acute exacerbations of chronic bronchitis: comparison of macrolides and moxifloxacin from the patient perspective. Author(s): Lorenz J, Thate-Waschke IM, Mast O, Kubin R, Rychlik R, Pfeil T, Daniel D, Tillotson GS. Source: J Int Med Res. 2001 March-April; 29(2): 74-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393351&dopt=Abstract
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Ultrastructural characteristics of the alveolar phagocytic cells from patients with various forms of chronic bronchitis. Author(s): Polosukhin VV. Source: Ultrastructural Pathology. 2001 November-December; 25(6): 419-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783906&dopt=Abstract
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Ultrastructural heterogeneity of the alveolar macrophages from tobacco smokers with chronic bronchitis. Author(s): Polosukhin VV, Manouilova LS, Romberger DJ, Matthews KI, Pirruccello SJ, West W, Daughton DM, Millatmal T, Umino T, Rennard SI. Source: Ultrastructural Pathology. 2001 January-February; 25(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297319&dopt=Abstract
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Uncomplicated acute bronchitis. Author(s): Heininger U. Source: Annals of Internal Medicine. 2001 November 6; 135(9): 839-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694110&dopt=Abstract
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Uncomplicated acute bronchitis. Author(s): Gonzales R, Sande MA. Source: Annals of Internal Medicine. 2000 December 19; 133(12): 981-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119400&dopt=Abstract
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Validity of the St George's respiratory questionnaire at acute exacerbation of chronic bronchitis: comparison with the Nottingham health profile. Author(s): Doll H, Duprat-Lomon I, Ammerman E, Sagnier PP. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 March; 12(2): 117-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639059&dopt=Abstract
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Variations in the prevalence across countries of chronic bronchitis and smoking habits in young adults. Author(s): Cerveri I, Accordini S, Verlato G, Corsico A, Zoia MC, Casali L, Burney P, de Marco R; European Community Respiratory Health Survey (ECRHS) Study Group. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 July; 18(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510810&dopt=Abstract
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What's in a name? Public knowledge, attitudes, and experiences with antibiotic use for acute bronchitis. Author(s): Gonzales R, Wilson A, Crane LA, Barrett PH Jr. Source: The American Journal of Medicine. 2000 January; 108(1): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059444&dopt=Abstract
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Wheezy bronchitis in childhood: a distinct clinical entity with lifelong significance? Author(s): Edwards CA, Osman LM, Godden DJ, Douglas JG. Source: Chest. 2003 July; 124(1): 18-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853497&dopt=Abstract
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Why are antibiotics prescribed for patients with acute bronchitis? A postintervention analysis. Author(s): Hueston WJ, Hopper JE, Dacus EN, Mainous AG 3rd. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 November-December; 13(6): 398-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117335&dopt=Abstract
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Workplace costs associated with acute exacerbation of chronic bronchitis: a comparison of moxifloxacin and levofloxacin. Author(s): Li-McLeod J, Perfetto EM. Source: Manag Care Interface. 2001 February; 14(2): 52-9. Erratum In: Manag Care Interface 2001 May; 14(5): 39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228817&dopt=Abstract
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Yoga therapy in chronic bronchitis. Author(s): Behera D. Source: J Assoc Physicians India. 1998 February; 46(2): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273114&dopt=Abstract
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CHAPTER 2. NUTRITION AND BRONCHITIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bronchitis.
Finding Nutrition Studies on Bronchitis 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 “bronchitis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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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 “bronchitis” (or a synonym): •
A survey of chronic bronchitis among brassware workers. Author(s): Epidemiology Division, Industrial Toxicology Research Centre, Lucknow, India. Source: Rastogi, S K Gupta, B N Mathur, N Husain, T Mahendra, P N Pangtey, B S Srivastava, S Ann-Occup-Hyg. 1992 June; 36(3): 283-94 0003-4878
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Action of tioxamast on various models of anaphylactic shock, hyperreactivity and bronchial inflammation in guinea-pigs. Author(s): Centre de Recherche Pierre Fabre, Castres, France. Source: Tarayre, J P Aliaga, M Barbara, M Tisseyre, N Tisne Versailles, J Couzinier, J P Arch-Int-Pharmacodyn-Ther. 1991 Mar-April; 310142-61 0003-9780
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Acupuncture induced immunoregulatory influence on the clinical state of patients suffering from chronic spastic bronchitis and undergoing long-term treatment with corticosteroids. Author(s): Specialistic Clinic for Outpatients, Allergy and Immunodeficiency Syndromeul, Warsaw, Poland. Source: Sliwinski, J Kulej, M Acupunct-Electrother-Res. 1989; 14(3-4): 227-34 0360-1293
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Amoxycillin/clavulanate in acute purulent exacerbations of chronic bronchitis. Source: Maesen, F P Davies, B I Baur, C J-Antimicrob-Chemother. 1987 March; 19(3): 373-83 0305-7453
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Bronchial inflammation and hyperreactivity after anaphylactic shock in guinea pigs actively sensitized by systemic or aerosol route. Author(s): Centre de Recherche Pierre Fabre, Castres, France. Source: Tarayre, J P Aliaga, M Barbara, M Malfetes, N Vieu, S Tisne Versailles, J Methods-Find-Exp-Clin-Pharmacol. 1991 March; 13(2): 93-7 0379-0355
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Chondroitin sulfate in sputum from patients with cystic fibrosis and chronic bronchitis. Author(s): Unite INSERM No. 16 and GDR CNRS No. 139, Lille, France. Source: Rahmoune, H Lamblin, G Lafitte, J J Galabert, C Filliat, M Roussel, P Am-JRespir-Cell-Mol-Biol. 1991 October; 5(4): 315-20 1044-1549
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Chronic bronchitis in textile workers in Lancashire. Source: Niven, R.M.L. Fletcher, A.M. Pickering, C.A.C. Fishwick, D. Warburton, C.J. Simpson, J.C.G. Oldham, L.A. Francis, H.C. Proc-Beltwide-Cotton-Conf. Memphis, Tenn. : National Cotton Council of America, 1991-. 1995. volume 1 page 313-316. 10592644
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Chronic bronchitis, work related respiratory symptoms, and pulmonary function in welders in New Zealand. Author(s): Department of Medicine, Wellington School of Medicine, New Zealand. Source: Bradshaw, L M Fishwick, D Slater, T Pearce, N Occup-Environ-Med. 1998 March; 55(3): 150-4 1351-0711
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Chronic bronchitis: when and how to treat. Author(s): Department of Medicine, University of Texas Health Center, Tyler 75710. Source: Nicotra, M B Rivera, M Semin-Respir-Infect. 1988 March; 3(1): 61-71 0882-0546
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Chronic Pseudomonas aeruginosa endobronchitis in rhesus monkeys: I. Effects of pentoxifylline on neutrophil influx. Author(s): Department of Medical Pathology, University of California, Davis.
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Source: Cheung, A T Moss, R B Leong, A B Novick, W J J-Med-Primatol. 1992 SepOctober; 21(7-8): 357-62 0047-2565 •
Combined effect of grain farming and smoking on lung function and the prevalence of chronic bronchitis. Author(s): Centre for Agricultural Medicine, University of Saskatchewan, Saskatoon, Canada. Source: Chen, Y Horne, S L McDuffie, H H Dosman, J A Int-J-Epidemiol. 1991 June; 20(2): 416-23 0300-5771
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Comparative study of early-season prophylaxis using ivermectin with lungworm vaccination in the control of parasitic bronchitis and gastroenteritis in cattle. Author(s): Department of Veterinary Pathology, Royal Veterinary College, University of London, Hatfield, Herts., Gt. Britain. Source: Jacobs, D E Foster, J Gowling, G Pilkington, J G Fox, M T Ryan, W G VetParasitol. 1989 November; 34(1-2): 45-56 0304-4017
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Comparison between aerosol and powder delivery system of fenoterol plus ipratropium bromide ('Duovent') in patients with asthma and chronic bronchitis. Author(s): Department of Medicine, Wellington Clinical School of Medicine, New Zealand. Source: Town, G I Pharmatherapeutica. 1988; 5(4): 246-8 0308-051X
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Control of parasitic bronchitis and gastroenteritis in grazing cattle by strategic prophylaxis with ivermectin. Source: Armour, J Bairden, K Pirie, H M Ryan, W G Vet-Rec. 1987 July 4; 121(1): 5-8 0042-4900
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Cost-effectiveness analysis of oral N-acetylcysteine as a preventive treatment in chronic bronchitis. Author(s): PHIDALSA Institute, Gumligen-Bern, Switzerland, Source: Grandjean, E M Berthet, P H Ruffmann, R Leuenberger, P Pharmacol-Res. 2000 July; 42(1): 39-50 1043-6618
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Effect of four-week treatment with oxitropium bromide on lung mucociliary clearance in patients with chronic bronchitis or asthma. Author(s): Department of Thoracic Medicine, Royal Free Hospital and Bracknell, Berkshire, UK. Source: Pavia, D Lopez Vidriero, M T Agnew, J E Taylor, R G Eyre Brook, A Lawton, W A Pellow, P G Clarke, S W Respiration. 1989; 55(1): 33-43 0025-7931
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Effect of heparin on the course of sulphur dioxide induced bronchitis in rats. Author(s): Department of Internal Medicine and Allergology, University Medical School, Wroclaw, Poland. Source: Krasnowska, M Kwasniewski, A Rabczynski, J Fal, A Kuryszko, J ArchImmunol-Ther-Exp-(Warsz). 1998; 46(1): 17-24 0004-069X
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Effect of sulfur dioxide and particulate pollutants on bronchitis in children--a risk analysis. Author(s): Department of Human Exposure Research and Epidemiology at the UFZCentre for Environmental Research, Leipzig, Germany.
[email protected] Source: Herbarth, O Fritz, G Krumbiegel, P Diez, U Franck, U Richter, M EnvironToxicol. 2001 June; 16(3): 269-76 1520-4081
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Effect of three sustained-release devices on parasitic bronchitis in first year calves. Author(s): Institute for Animal Science and Health, Lelystad, The Netherlands.
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Source: Borgsteede, F H van der Linden, J N Cornelissen, J B Gaasenbeek, C P Ascher, F Vet-Rec. 1998 June 20; 142(25): 696-9 0042-4900 •
Effects of captopril combined with oxygen therapy at rest and on exercise in patients with chronic bronchitis and pulmonary hypertension. Author(s): Department of Medecine, Hopital A. Michallon, Joseph Fourier University, Grenoble, France. Source: Pison, C M Wolf, J E Levy, P A Dubois, F Brambilla, C G Paramelle, B Respiration. 1991; 58(1): 9-14 0025-7931
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Effects of corticosteroids in “chronic bronchitis” and “chronic obstructive airway disease”. Author(s): Department of Pulmonology, University Hospital, Groningen, The Netherlands. Source: Postma, D S Renkema, T E Koeter, G H Agents-Actions-Suppl. 1990; 3041-57 0379-0363
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Enoxacin in acute exacerbations of chronic bronchitis: a comparison with amoxycillin. Author(s): Department of Respiratory Diseases, Brugmann University Hospital, Brussels, Belgium. Source: Prigogine, T Glupczynski, Y Carpiaux, J P Blogie, M Yourassowsky, E Schmerber, J S J-Antimicrob-Chemother. 1988 February; 21 Suppl B131-6 0305-7453
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Field evaluation of a topical doramectin formulation for the chemoprophylaxis of parasitic bronchitis in calves. Author(s): Faculty of Veterinary Medicine, University of Gent, Department of Virology, Parasitology and Immunology, Merelbeke, Belgium. Source: Vercruysse, J Dorny, P Claerebout, E Weatherley, A Vet-Parasitol. 1998 February 28; 75(2-3): 169-79 0304-4017
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Identification of a novel cleavage activity of the first papain-like proteinase domain encoded by open reading frame 1a of the coronavirus Avian infectious bronchitis virus and characterization of the cleavage products. Author(s): Institute of Molecular Agrobiology, National University of Singapore, Singapore 117604, Singapore. Source: Lim, K P Ng, L F Liu, D X J-Virol. 2000 February; 74(4): 1674-85 0022-538X
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Immunity to parasitic bronchitis of yearling cattle treated with ivermectin during their first grazing season. Author(s): Veterinary Research Laboratory, Stormont, Belfast. Source: Taylor, S M Mallon, T R Green, W P McLoughlin, M F Bryson, D G Vet-Rec. 1988 October 8; 123(15): 391-5 0042-4900
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Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. Author(s): Institute of Molecular Agrobiology, 1 Research Link, The National University of Singapore, Singapore 117406, Singapore.
[email protected] Source: Liu, C Xu, H Y Liu, D X J-Virol. 2001 July; 75(14): 6402-9 0022-538X
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Lipid peroxidation--antioxidant activity system in erythrocytes of patients with chronic bronchitis inhaling and not inhaling ozone. Author(s): Russian State Medical University, Moscow. Source: Abdrashitova, N F RomaNovember, Y A Bull-Exp-Biol-Med. 2001 September; 132(3): 884-6 0007-4888
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N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study. Author(s): Department of Respiratory Medicine, Alborg Hospital, Denmark. Source: Dueholm, M Nielsen, C Thorshauge, H Evald, T Hansen, N C Madsen, H D Maltbaek, N Respir-Med. 1992 March; 86(2): 89-92 0954-6111
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Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis. Author(s): Ciba-Geigy Pharmaceuticals, Horsham, West Sussex. Source: Parr, G D Huitson, A Br-J-Dis-Chest. 1987 October; 81(4): 341-8 0007-0971
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Preliminary clinical assessment of the leukocyte migration inhibition test (LMIT) with cow's milk antigens in the diagnosis of recurrent obturative bronchitis in infants. Author(s): Newborns' Department Neonatology, Child's Health Centre, Warsaw. Source: Maciejewski, Z Piatosa, B Pneumonol-Alergol-Pol. 1992; 60 Suppl 2122-4 08677077
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Prevention of parasitic gastroenteritis and parasitic bronchitis in first and second season grazing cattle. Author(s): Department of Veterinary Parasitology, Faculty of Veterinary Medicine, Ghent, Belgium. Source: Hollanders, W Berghen, P Dorny, P Hilderson, H Vercruysse, J Ryan, W G VetRec. 1992 April 18; 130(16): 355-6 0042-4900
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Recent advances in diagnosis and management of chronic bronchitis and emphysema. Author(s): Division of Pulmonary, Critical Care, and Sleep Medicine, Veterans Administration Palo Alto Health Care System, and Stanford University School of Medicine, Palo Alto, California 94304, USA.
[email protected] Source: Chitkara, Rajinder K Sarinas, Priscilla S A Curr-Opin-Pulm-Med. 2002 March; 8(2): 126-36 1070-5287
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Risk of osteoporosis in men with chronic bronchitis. Author(s): Department of Rheumatology, Saint Pierre University Hospital, Free Universities of Brussels, Belgium. Source: Praet, J P Peretz, A Rozenberg, S Famaey, J P Bourdoux, P Osteoporos-Int. 1992 September; 2(5): 257-61 0937-941X
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Safety and effectiveness of lomefloxacin in patients with acute exacerbation of chronic bronchitis (AECB) chronically treated with oral theophyllines. Author(s): UO Fisiopatologia Respiratoria, Azienda Ospedaliera Senese, Policlinico Le Scotte, Siena, Italy.
[email protected] Source: Melani, A S Pirrelli, M Sarlo, F Cantoni, V J-Chemother. 2001 December; 13(6): 628-34 1120-009X
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Sequence analysis of the S1 glycoprotein of infectious bronchitis viruses: identification of a novel genotypic group in Australia. Source: Sapats, S.I. Ashton, F. Wright, P.J. Ignjatovic, J. J-gen-virol. Reading : Society for General Microbiology. March 1996. volume 77 (pt.3) page 413-418. 0022-1317
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Some aspects of “deep lung” cellular immunity in chronic bronchitis before and after therapy with tiopronin. Source: Fraschini, F Scaglione, F Coppi, G Piazza, G Marchi, E Montoli, C C Scarpazza, G Int-J-Clin-Pharmacol-Res. 1987; 7(2): 129-33 0251-1649
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The role of the inflammatory response in chronic bronchitis: therapeutic implications. Author(s): Section of Pulmonary/Critical Care Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
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Source: Nelson, S Summer, W R Mason, C M Semin-Respir-Infect. 2000 March; 15(1): 2431 0882-0546 •
Theophylline in serum and in bronchoalveolar lavage (BAL) in atopic bronchial asthma and chronic bronchitis. Author(s): Department of Internal Medicine, Central Clinical Hospital, Military Medical Academy, Warsaw, Poland. Source: Plusa, T Jozefczak, E Raczka, A Allergol-Immunopathol-(Madr). 1989 JanFebruary; 17(1): 29-32 0301-0546
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Thymopentine treatment improves clinical and immunological functions in aged subjects with chronic bronchitis. Author(s): Istituto Scientifico San Raffaele, Ospedale San Raffaele, Milano. Source: Pavoni, D Crosti, F Ciboddo, G F Sabbadini, M G Baldini, V Navone, P Bellone, M Rugarli, C Boll-Ist-Sieroter-Milan. 1987; 66(4): 308-15 0021-2547
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Traditional Chinese medicine in treatment of bronchitis and bronchial asthma. Author(s): Henan Provincial Hospital of Traditional Chinese Medicine, Henan Province. Source: Chen, A J-Tradit-Chin-Med. 1998 March; 18(1): 71-6 0254-6272
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Transition from normal to hypersecretory bronchial mucus in a canine model of bronchitis: changes in yield and composition. Author(s): Department of Pathology, Children's Hospital, Boston, MA 02115. Source: Bhaskar, K R Drazen, J M O'Sullivan, D D Scanlon, P M Reid, L M Exp-LungRes. 1988; 14(1): 101-20 0190-2148
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Treatment of cough and dyspnea due to acute bronchitis by plaster for cough and dyspnea--a report of 735 cases. Author(s): Zhongxiang Municipal Hospital of Traditional Chinese Medicine, Zhongxiang City 431900, Hubei Province. Source: Chen, Z Zhou, W Gao, J Sun, J J-Tradit-Chin-Med. 2002 March; 22(1): 5-8 02546272
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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to bronchitis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C and Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,935,00.html Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html
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Food and Diet Garlic Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Garlic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10046,00.html Natural Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Refined Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Sugar Alcohols Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND BRONCHITIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bronchitis. 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 bronchitis 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 “bronchitis” (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 bronchitis: •
Acupuncture induced immunoregulatory influence on the clinical state of patients suffering from chronic spastic bronchitis and undergoing long-term treatment with corticosteroids. Author(s): Sliwinski J, Kulej M. Source: Acupuncture & Electro-Therapeutics Research. 1989; 14(3-4): 227-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2576342&dopt=Abstract
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Acute bronchitis due to cotton plant polyphenols. Author(s): Kilburn KH. Source: Annals of the New York Academy of Sciences. 1974; 221: 335-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4522556&dopt=Abstract
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Alternative therapies for chronic bronchitis. Author(s): Jones KL, Robbins RA.
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Source: The American Journal of the Medical Sciences. 1999 August; 318(2): 96-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10452567&dopt=Abstract •
An investigation of renal function in chronic bronchitis. Author(s): Daggett P. Source: Postgraduate Medical Journal. 1977 January; 53(615): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=17853&dopt=Abstract
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Are beta2-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systematic review. Author(s): Smucny JJ, Flynn CA, Becker LA, Glazier RH. Source: The Journal of Family Practice. 2001 November; 50(11): 945-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711010&dopt=Abstract
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Binding and diffusion characteristics of 14C EDTA and 99mTc DTPA in respiratory tract mucus glycoprotein from patients with chronic bronchitis. Author(s): Cheema MS, Groth S, Marriott C. Source: Thorax. 1988 September; 43(9): 669-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3143162&dopt=Abstract
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Breathing retraining. Mount Sinai Hospital emphysema-chronic bronchitis clinic. Author(s): Westreich N, Paguyo N, Cohen S, Grismer J. Source: Minn Med. 1970 June; 53(6): 621-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5449271&dopt=Abstract
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Care for emphysema and chronic bronchitis. Author(s): Petty TL, Neff TA. Source: Annals of Internal Medicine. 1970 March; 72(3): 435-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5415427&dopt=Abstract
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Chest physical therapy in patients with acute exacerbation of chronic bronchitis: effectiveness of three methods. Author(s): Bellone A, Lascioli R, Raschi S, Guzzi L, Adone R. Source: Archives of Physical Medicine and Rehabilitation. 2000 May; 81(5): 558-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10807091&dopt=Abstract
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Chronic bronchitis and emphysema. Author(s): Webster JR Jr, Addington WW. Source: Postgraduate Medicine. 1971 December; 50(6): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5128034&dopt=Abstract
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Chronic bronchitis in the 1990s: up-to-date treatment. Author(s): Clarke SW. Source: Respiration; International Review of Thoracic Diseases. 1991; 58 Suppl 1: 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1925078&dopt=Abstract
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Chronic obstructive pulmonary disease: current comprehensive care for emphysema and bronchitis. Author(s): Johannsen JM. Source: The Nurse Practitioner. 1994 January; 19(1): 59-67. Review. Erratum In: Nurse Pract 1994 March; 19(3): 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8139803&dopt=Abstract
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Editorial: Does treatment for severe emphysema and chronic bronchitis really help? (A response). Author(s): Petty TL. Source: Chest. 1974 February; 65(2): 124-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4810668&dopt=Abstract
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Effect of chest wall vibrations on pulmonary function in chronic bronchitis. Author(s): Rivington-Law BA, Epstein SW, Thompson GL, Corey PN. Source: Chest. 1984 March; 85(3): 378-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6697796&dopt=Abstract
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Effects of guided imagery in patients with chronic bronchitis and emphysema. Author(s): Moody LE, Fraser M, Yarandi H. Source: Clinical Nursing Research. 1993 November; 2(4): 478-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8220200&dopt=Abstract
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Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial. Author(s): Matthys H, Eisebitt R, Seith B, Heger M. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 7-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807337&dopt=Abstract
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Esberitox N as supportive therapy when providing standard antibiotic treatment in subjects with a severe bacterial infection (acute exacerbation of chronic bronchitis). A multicentric, prospective, double-blind, placebo-controlled study. Author(s): Hauke W, Kohler G, Henneicke-Von Zepelin HH, Freudenstein J. Source: Chemotherapy. 2002 December; 48(5): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476043&dopt=Abstract
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History of the treatment of chronic bronchitis. Author(s): Ziment I. Source: Respiration; International Review of Thoracic Diseases. 1991; 58 Suppl 1: 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1925077&dopt=Abstract
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Long-term treatment of chronic bronchitis with positive expiratory pressure mask and chest physiotherapy. Author(s): Christensen EF, Nedergaard T, Dahl R. Source: Chest. 1990 March; 97(3): 645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2106412&dopt=Abstract
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Measurement of tracheobronchial clearance after sauna in subjects with chronic bronchitis. Author(s): van Hengstum M, Festen J, Corstens F. Source: Thorax. 1991 October; 46(10): 732-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1750021&dopt=Abstract
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Naturheilverfahren bei einer Patientin mit chronischer Bronchitis und asthmoider Reaktion. Author(s): Ludescher G, Pflugbeil C, Riesberg A, Buhring M. Source: Forschende Komplementarmedizin. 1998 April; 5(2): 87-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9761990&dopt=Abstract
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No effect of oral high frequency oscillation combined with forced expiration manoeuvres on tracheobronchial clearance in chronic bronchitis. Author(s): van Hengstum M, Festen J, Beurskens C, Hankel M, van den Broek W, Corstens F. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1990 January; 3(1): 14-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2311725&dopt=Abstract
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Observations on the preparation and stability of infectious bronchitis virus hemagglutination antigen from virus propagated in chicken embryos and chicken kidney cell cultures. Author(s): King DJ. Source: Avian Dis. 1984 April-June; 28(2): 504-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6331366&dopt=Abstract
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Outpatient care for patients with chronic airway obstruction--emphysema and bronchitis. Author(s): Neff TA, Petty TL.
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Source: Chest. 1971 August; 60(2): Suppl: 11S-17S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5567449&dopt=Abstract •
Oxygen therapy in hypoxic chronic bronchitis. Feasibility of nocturnal oxygen supplementation at home after hospital-induced improvement. Author(s): Mays EE. Source: J Chronic Dis. 1969 December; 22(6): 421-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5370514&dopt=Abstract
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Pharmacokinetics of [18F]fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography. Author(s): Fischman AJ, Livni E, Babich JW, Alpert NM, Bonab A, Chodosh S, McGovern F, Kamitsuka P, Liu YY, Cleeland R, Prosser BL, Correia JA, Rubin RH. Source: Antimicrobial Agents and Chemotherapy. 1996 March; 40(3): 659-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8851589&dopt=Abstract
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Preventive strategies for young children with wheezing bronchitis. Author(s): Rylander E. Source: Acta Paediatrica (Oslo, Norway : 1992). 1997 June; 86(6): 554-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9202786&dopt=Abstract
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Psychophysiologic predictors of weaning from mechanical ventilation in chronic bronchitis and emphysema. Author(s): Moody LE, Lowry L, Yarandi H, Voss A. Source: Clinical Nursing Research. 1997 November; 6(4): 311-30; Discussion 330-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384053&dopt=Abstract
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Regular balloon inflation for patients with chronic bronchitis: a randomised controlled trial. Author(s): Chauhan AJ, McLindon JP, Dillon P, Sawyer JP, Gray L, Leahy BC. Source: Bmj (Clinical Research Ed.). 1992 June 27; 304(6843): 1668-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1633520&dopt=Abstract
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Rehabilitation in chronic bronchitis and bronchial asthma. Author(s): Trendelenburg F, Reinert M. Source: Scand J Respir Dis Suppl. 1974; 89: 41-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4528710&dopt=Abstract
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Respiratory physical therapy in the treatment of chronic bronchitis. Author(s): Burford JG, George RB.
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Source: Seminars in Respiratory Infections. 1988 March; 3(1): 55-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3283882&dopt=Abstract •
Solanum xanthocarpum (Kantakari) in chronic bronchitis, bronchial asthma and nonspecific unproductive cough. (An experimental and clinical co-relation). Author(s): Bector NP, Puri AS. Source: J Assoc Physicians India. 1971 October; 19(10): 741-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5132261&dopt=Abstract
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Studies on the use of warming kidney regime in senile chronic bronchitis. Author(s): Shen ZY, Jiang XH, Zha LL, Chen WH, Chen SZ, Zhang RJ, Chen JQ, Chen XZ, Shi SZ, Zhou XX. Source: J Tradit Chin Med. 1983 December; 3(4): 295-302. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6562303&dopt=Abstract
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Study on clinical properties and mechanisms of action of Petasites in bronchial asthma and chronic obstructive bronchitis. Author(s): Ziolo G, Samochowiec L. Source: Pharmaceutica Acta Helvetiae. 1998 February; 72(6): 378-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556439&dopt=Abstract
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The circulation in patients with chronic bronchitis and emphysema at rest and during exercise, with special reference to the influence of changes in blood viscosity and blood volume on the pulmonary circulation. Author(s): Segel N, Bishop JM. Source: The Journal of Clinical Investigation. 1966 October; 45(10): 1555-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5925514&dopt=Abstract
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The effect of acupuncture on the clinical state of patients suffering from chronic spastic bronchitis and undergoing long-term treatment with corticosteroids. Author(s): Sliwinski J, Matusiewicz R. Source: Acupuncture & Electro-Therapeutics Research. 1984; 9(4): 203-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6152511&dopt=Abstract
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The efficiency of thermoregulation in adult patients with bronchial asthma and chronic bronchitis after climatic treatment at the Baltic seaside. Author(s): Maczynski B. Source: Pol Med Sci Hist Bull. 1970 October; 13(4): 179-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5489792&dopt=Abstract
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Traditional Chinese medicine in treatment of bronchitis and bronchial asthma. Author(s): Chen A.
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Source: J Tradit Chin Med. 1998 March; 18(1): 71-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437268&dopt=Abstract •
Treatment of cough and dyspnea due to acute bronchitis by plaster for cough and dyspnea--a report of 735 cases. Author(s): Chen Z, Zhou W, Gao J, Sun J. Source: J Tradit Chin Med. 2002 March; 22(1): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11977523&dopt=Abstract
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Yoga therapy in chronic bronchitis. Author(s): Behera D. Source: J Assoc Physicians India. 1998 February; 46(2): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273114&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: 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/
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The following is a specific Web list relating to bronchitis; 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 Asthma Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Integrative Medicine Communications; www.drkoop.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com Common Cold Source: Integrative Medicine Communications; www.drkoop.com Cough Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Integrative Medicine Communications; www.drkoop.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Laryngitis Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com
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Alternative Therapy Acupuncture Source: Integrative Medicine Communications; www.drkoop.com Aromatherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,664,00.html Color Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,683,00.html Ionized Air (negative Ions) Source: Healthnotes, Inc.; www.healthnotes.com Osteopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724,00.html Tai Chi Source: Integrative Medicine Communications; www.drkoop.com •
Chinese Medicine Beiling Jiaonang Alternative names: Beiling Capsules Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Gancao Jingao Alternative names: Liquorice Extract; Gancao JingaoExtractum Glycyrrhizae
Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Manshanhong Alternative names: Dahurian Rhododendron Leaf; Folium Rhododendri Daurici Source: Chinese Materia Medica Manshanhongyou Alternative names: Daurian Rhododendron Oil; Oleum Rhododendri Daurici Source: Chinese Materia Medica Mujingye Alternative names: Hempleaf Negundo Chastetree Leaf; Folium Viticis Negundo Source: Chinese Materia Medica Mujingyou Alternative names: Negundo Chastetree Oil; Oleum Viticis Negundo Source: Chinese Materia Medica Reyanning Keli Alternative names: Reyanning Granules; Reyanning Keli
(Rey Yan Ning Ke Li) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China
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Yanbaicaisu Alternative names: Bergenin; Yanbaicaisu (Yan Bai Cai Su); Bergeninum Source: Chinese Materia Medica •
Homeopathy Antimonium Tartaricum Source: Healthnotes, Inc.; www.healthnotes.com Bryonia Source: Healthnotes, Inc.; www.healthnotes.com Calcarea Carbonica Source: Healthnotes, Inc.; www.healthnotes.com Causticum Source: Healthnotes, Inc.; www.healthnotes.com Chamomilla Source: Healthnotes, Inc.; www.healthnotes.com Dulcamara Source: Healthnotes, Inc.; www.healthnotes.com Hepar Sulphuris Calcareum Source: Healthnotes, Inc.; www.healthnotes.com Kali Bichromicum Source: Healthnotes, Inc.; www.healthnotes.com Pulsatilla Source: Healthnotes, Inc.; www.healthnotes.com Silicea (silica) Source: Healthnotes, Inc.; www.healthnotes.com Sulphur Source: Healthnotes, Inc.; www.healthnotes.com
•
Herbs and Supplements Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Angelica Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca
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Anise Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Astragalus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10006,00.html Barberry Alternative names: Berberis vulgaris, Berberry Source: Integrative Medicine Communications; www.drkoop.com Berberis Vulgaris Source: Integrative Medicine Communications; www.drkoop.com Berberry Source: Integrative Medicine Communications; www.drkoop.com Blood Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Bromelain Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Catnip Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Chinese Scullcap Alternative names: Scutellaria baicalensis Source: Healthnotes, Inc.; www.healthnotes.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Coleus Forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com
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Damiana Alternative names: Turnera diffusa Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Alternative names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html Elecampane Alternative names: Inula helenium Source: Healthnotes, Inc.; www.healthnotes.com Elecampane Source: Prima Communications, Inc.www.personalhealthzone.com Elecampane Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca English Lavendar Source: Integrative Medicine Communications; www.drkoop.com Ephedra Alternative names: Ephedra sinensis, Ma huang Source: Integrative Medicine Communications; www.drkoop.com Ephedra Sinensis Source: Integrative Medicine Communications; www.drkoop.com Eucalyptus Alternative names: Eucalyptus globulus Source: Healthnotes, Inc.; www.healthnotes.com Fennel Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Fenugreek Alternative names: Trigonella foenum-graecum Source: Healthnotes, Inc.; www.healthnotes.com Fenugreek Source: Prima Communications, Inc.www.personalhealthzone.com Fenugreek Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca
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French Lavendar Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Glabra Source: Integrative Medicine Communications; www.drkoop.com Golden Rod Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Gotu Kola Alternative names: Centella asiatica Source: Healthnotes, Inc.; www.healthnotes.com Grindelia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Horehound Alternative names: Marrubium vulgare Source: Healthnotes, Inc.; www.healthnotes.com Horehound Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Horehound Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10036,00.html Horseradish Alternative names: Cochlearia armoracia Source: Healthnotes, Inc.; www.healthnotes.com Hyssop Alternative names: Hyssopus officinalis Source: Healthnotes, Inc.; www.healthnotes.com Hyssop Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Ipratropium Bromide Source: Healthnotes, Inc.; www.healthnotes.com
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Ivy Leaf Alternative names: Hedera helix Source: Healthnotes, Inc.; www.healthnotes.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lavandula Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Lavender Alternative names: Lavandula angustifolia, English Lavendar, French Lavendar Source: Integrative Medicine Communications; www.drkoop.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Limetree Source: Integrative Medicine Communications; www.drkoop.com Linden Alternative names: Tilia cordata, Tilia platyphyllos, Limetree Source: Integrative Medicine Communications; www.drkoop.com Lobelia Alternative names: Lobelia inflata Source: Healthnotes, Inc.; www.healthnotes.com Lobelia Alternative names: Lobelia inflata, Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Lobelia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Lobelia Inflata Source: Integrative Medicine Communications; www.drkoop.com Loracarbef Source: Healthnotes, Inc.; www.healthnotes.com Ma Huang Source: Integrative Medicine Communications; www.drkoop.com Ma Huang Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca
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Marshmallow Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Mullein Alternative names: Verbascum thapsus Source: Healthnotes, Inc.; www.healthnotes.com Mullein Flower Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,865,00.html Nac (n-acetylcysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html N-acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com N-acetyl Cysteine (nac) Source: Prima Communications, Inc.www.personalhealthzone.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pau D'arco Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,811,00.html Plantago Major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Plantain Alternative names: Plantago lanceolata, Plantago major Source: Healthnotes, Inc.; www.healthnotes.com Plantain Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Pleurisy Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Quinolones Source: Integrative Medicine Communications; www.drkoop.com
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Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Reishi Source: Prima Communications, Inc.www.personalhealthzone.com Rosmarinus Alternative names: Rosemary; Rosmarinus officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Skunk Cabbage Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Slippery Elm Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10056,00.html Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Sundew Alternative names: Drosera rotundifolia, Drosera ramentacea, Drosera intermedia, Drosera anglica Source: Healthnotes, Inc.; www.healthnotes.com ThyMen Alternative names: Thymus vulgaris Source: Healthnotes, Inc.; www.healthnotes.com ThyMen Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Thymus Extracts Source: Healthnotes, Inc.; www.healthnotes.com Tilia Cordata Source: Integrative Medicine Communications; www.drkoop.com Tilia Platyphyllos Source: Integrative Medicine Communications; www.drkoop.com Tylophora Alternative names: Tylophora indica, Tylophora asthmatica Source: Healthnotes, Inc.; www.healthnotes.com
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Wild Cherry Bark Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Yerba Santa Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON BRONCHITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to bronchitis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “bronchitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bronchitis, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Bronchitis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to bronchitis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Analysis of Structural Genes and Experimental Recombination between Virus and Transfected Rna Fragments of Avian Infectious Bronchitis Virus by Brooks, Judy Elaine; Phd from Texas A&m University, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3060775
•
Envelope Protein Localization and Interactions in Infectious Bronchitis Virus Budding at Golgi Membranes by Corse, Emily R.; Phd from The Johns Hopkins University, 2003, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3068136
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Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND BRONCHITIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bronchitis.
Recent Trials on Bronchitis The following is a list of recent trials dedicated to bronchitis.8 Further information on a trial is available at the Web site indicated. •
Cardiopulmonary Effects of Particulate Exposure Condition(s): Respiratory Tract Diseases; Cardiac Diseases; Bronchitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: The aim of this study is to assess cardiac rate and respiratory responses and rhythm after workplace exposure to combustion particulates. A repeated measurement study is being performed on acute boilermakers (apprentices and journeymen). A stratified analysis is then done on those with and without chronic bronchitis, after adjustment for relevant covariates. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011310
•
Study Evaluating the Safety and Efficacy of Infliximab in Subjects with Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Condition(s): Pulmonary Disease, Chronic Obstructive; Chronic Bronchitis; Emphysema Study Status: This study is currently recruiting patients. Sponsor(s): Centocor
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: The purpose of this study is to determine the safety and efficacy of infliximab in patients with moderate to severe Chronic Obstructive Pulmonary Disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056264 •
To evaluate the long-term safety of (R,R)-formoterol in subjects with COPD Condition(s): Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; Emphysema Study Status: This study is currently recruiting patients. Sponsor(s): Sepracor, Inc. Purpose - Excerpt: The purpose of this study is to determine the long-term safety of (R,R)-formoterol over a period of 12 months in subjects with COPD Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064415
•
Yoga for Treating Shortness of Breath in Chronic Obstructive Pulmonary Disease (COPD) Condition(s): Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Pulmonary Emphysema; Chronic Bronchitis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of yoga in reducing shortness of breath in people with chronic obstructive pulmonary disease (COPD). Patients in this study must have moderate to severe COPD and be primarily limited by shortness of breath. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051792
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately
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5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “bronchitis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
•
For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
•
For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON BRONCHITIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “bronchitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bronchitis, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Bronchitis By performing a patent search focusing on bronchitis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on bronchitis: •
.beta.2-adrenergic receptor agonists Inventor(s): Choi; Seok-Ki (Palo Alto, CA), Moran; Edmund J. (San Francisco, CA) Assignee(s): Theravance, Inc. (South San Francisco, CA) Patent Number: 6,541,669 Date filed: June 2, 1999 Abstract: Disclosed are multibinding compounds which are.beta.2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor. Excerpt(s): This invention relates to novel multibinding compounds (agents) that are.beta.2 adrenergic receptor agonists and pharmaceutical compositions comprising such compounds. Accordingly, the multibinding compounds and pharmaceutical compositions of this invention are useful in the treatment and prevention of respiratory diseases such as asthma and chronic bronchitis. They are also useful in the treatment of nervous system injury and premature labor.sup.2 Strosberg, A. D. "Structure, Function, and Regulation of Adrenergic Receptors" Protein Sci. 2, 1198-1209 (1993).sup.3 BeckSickinger, A. G. "Structure Characterization and Binding Sites of G-Protein-coupled Receptors" DDT, 1, 502-513, (1996). Web site: http://www.delphion.com/details?pn=US06541669__
•
Anti-allergy anti-inflammatory composition Inventor(s): Jain; Rajesh (New Delhi, IN), Singh; Amarjit (New Delhi, IN) Assignee(s): Panacea Biotec Limited (New Delhi, IN) Patent Number: 6,258,816 Date filed: October 26, 1998 Abstract: A novel composition of Nimesulide and salts thereof and Cetrizine possessing antileukotriene, antihistaminic, antiallergic and antiinflammatory action is disclosed. The composition is useful in the cure of allergic disorders such as rhinitis, bronchitis, asthama, urticaria and the like. Excerpt(s): The present invention relates to a novel antileukotriene, antihistaminic, antiallergic and antiinflammatory composition of non-steroidal antiinflammatory sulfonanilide and, salts thereof with second generation anti-histamines (H.sub.1, blockers). More particularly the invention relates to a novel composition of Nimesulide and Cetirizine in a pharmaceutically acceptable combination in a suitable pharmaceutical base acceptable and excipients. More particularly the invention relates to a composition for use in allergic disorders namely rhinitis, bronchitis, asthma, urticaria and the like. Web site: http://www.delphion.com/details?pn=US06258816__
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•
Avian polynucleotide formula Inventor(s): Audonnet; Jean-Christophe (Lyons, FR), Bouchardon; Annabelle (Lyons, FR), Riviere; Michel (Ecully, FR) Assignee(s): Merial (Lyons, FR) Patent Number: 6,221,362 Date filed: January 15, 1999 Abstract: The avian vaccine formula comprises at least three polynucleotide vaccine valencies each comprising a plasmid integrating, so as to express it in vivo in the host cells, a gene with one avian pathogen valency, these valencies being selected from the group consisting of Marek's disease virus, Newcastle disease virus, infectious bursal disease virus, infectious bronchitis virus, infectious anaemia virus, the plasmids comprising, for each valency, one or more of the genes selected from the group consisting of gB and gD for the Marek's disease virus, HN and F for the Newcastle disease virus, VP2 for the infectious bursal disease virus, S, M and N for the infectious bronchitis virus, C+NS1 for the infectious anaemia virus. Excerpt(s): All of the above-mentioned applications, as well as all documents cited herein and documents referenced or cited in documents cited herein, are hereby incorporated herein by reference. Vectors of vaccines or immunological compositions of the aforementioned applications, as well as of documents cited herein or documents referenced or cited in documents cited herein or portions of such vectors (e.g., one or more or all of regulatory sequences such as DNA for promoter, leader for secretion, terminator), may to the extent practicable with respect to the preferred host of this application, also be employed in the practice of this invention; and, DNA for vectors of vaccines or immunological compositions herein can be obtained from available sources and knowledge in the art, e.g., GeneBank, such that from this disclosure, no undue experimentation is required to make or use such vectors. The present invention relates to a vaccine formula allowing the vaccination of avian species, in particular chickens. It also relates to a corresponding method of vaccination. Associations of vaccines against a number of viruses responsible for pathologies in chicken have already been proposed in the past. Web site: http://www.delphion.com/details?pn=US06221362__
•
Avian recombinant live vaccine using, as vector, the avian infectious laryngotracheitis Inventor(s): Audonnet; Jean-Christophe (Lyons, FR), Bublot; Michel (St Genis les Olieres, FR), Laplace; Eliane (Oullins, FR) Assignee(s): Merial (Lyons, FR) Patent Number: 6,306,400 Date filed: July 28, 1999 Abstract: The avian recombinant live vaccine comprises, as vector, an ILTV virus comprising and expressing at least one heterologous nucleotide sequence, this nucleotide sequence being inserted into the insertion locus formed by the intergenic region situated between the stop codons of the ORF D and ORF E of ILTV and which, in a specific ILTV strain, is defined between nucleotides 3873 and 4260 in SEQ ID No:1. The heterologous nucleotide sequence may be under the control of a strong eukaryotic promoter, such as the CMV-IE promoter, and may be derived from the Newcastle
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disease virus, Marek's disease virus, the infectious bursal disease virus, the infectious bronchitis virus, the chicken anaemia virus and the chicken pneumovirosis virus. Multivalent vaccine formula comprising at least two live vaccines according to the invention. ILTV virus thus recombined. Excerpt(s): Not applicable. The present invention relates to vaccines for avian use based on infectious laryngotracheitis virus (ILTV) into which there has been inserted, by genetic recombination, at least one heterologous nucleotide sequence in particular encoding and expressing an antigenic polypeptide from an avian pathogenic agent, under conditions ensuring immunization leading to effective protection of the vaccinated animal against the said pathogenic agent. The infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus (B. Roizman, Arch. Virol. 1992. 123. 425-449) which causes a major respiratory pathology (infectious laryngotracheitis or ILT) in chicken (L. E. Hanson and T. J. Bagust, Diseases of Poultry 9th edn 1991. pp 485-495. Ames, Iowa State University Press). The vaccines currently available against this condition contain an attenuated strain which can be administered by various routes including the intranasal, conjunctival and cloacal routes, in drinking water and by aerosol (L. E. Hanson and T. J. Bagust (1991). Web site: http://www.delphion.com/details?pn=US06306400__ •
Avian recombinant live vaccine using, as vector, the avian infectious laryngotracheitis virus Inventor(s): Audonnet; Jean-Christophe (Lyons, FR), Bublot; Michel (Les Olieres, FR), Riviere; Michel (Ecully, FR) Assignee(s): Merial (Lyons, FR) Patent Number: 6,153,199 Date filed: December 23, 1998 Abstract: The living recombinant avian vaccine comprises, as a vector, an ILTV virus comprising and expressing at least one heterologous nucleotide sequence, this nucleotide sequence being inserted in the insertion locus defined between the nucleotides 1624 and 3606 at the SEQ ID NO: 5. The vaccine may in particular comprise a sequence coding for an antigen of an avian pathogenic agent selected among the group consisting of the Newcastle disease virus (NDV), the infections bursal virus (IBDV), the Marek disease virus (MDV), the infectious bronchitis virus (IBV), the chicken anaemia virus (CAV), thee chicken pneumovirosis virus, preferably under the control of a strong eukariotic promoter. A multivalent vaccine formula is also disclosed. Excerpt(s): The present invention relates to vaccines for avian use based on infectious laryngotracheitis virus (ILTV) into which there has been inserted, by genetic recombination, at least one heterologous nucleotide sequence in particular encoding and expressing an antigenic polypeptide from an avian pathogenic agent, under conditions ensuring immunization leading to effective protection of the vaccinated animal against the said pathogenic agent. The infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus (B. Roizman, Arch. Virol. 1992. 123. 425-449) which causes a major respiratory pathology (infectious laryngotracheitis or ILT) in chicken (L. E. Hanson and T. J. Bagust, Diseases of Poultry 9th edn 1991. pp 485-495. Ames, Iowa State University Press). The vaccines currently available against this condition contain an attenuated strain which can be administered by various routes including the intranasal, conjunctival and cloacal routes, in drinking water and by aerosol (L. E. Hanson and T. J.
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Bagust, Diseases of Poultry 9th Edition 1991. pp 485-495. Ames, Iowa State University Press). Studies of the molecular biology of the ILTV virus have made it possible to characterize the viral genome (M. A. Johnson et al., Arch. Virol. 1991. 119. 181-198) and to identify some of the virus genes (A. M. Griffin, J. Gen. Virol. 1989. 70. 3085-3089) including the genes encoding thymidine kinase (UL23) (A. M. Griffin and M. E. G. Boursnell, J. Gen. Virol. 1990. 71. 841-850; C. L. Keeler et al., Avian Dis. 1991. 35. 920929), the glycoprotein gB (UL27) (A. M. Griffin, J. Gen. Virol. 1991. 72. 393-398; K. Kongsuwan et al., Virology 1991. 184. 404-410; D. J. Poulsen et al., Virus Genes 1991. 5. 335-347), the glycoprotein gC (UL44) (D. H. Kingsley et al., Virology 1994. 203. 336-343), the capsid protein p40 (UL26) (A. M. Griffin, Nucl. Acids Res. 1990. 18. 3664), the protein homologous to the ICP4 protein of herpes simplex (HSV-1) (M. A. Johnson et a)., Virus Research 1995. 35. 193-204), the proteins homologous to the proteins ICP27 (UL54), glycoprotein gK (UL53) and DNA helicase (UL52) from :HSV-1 (M. A. Johnson et al., Arch. Virol. 1995. 140. 623-634), ribonucleotide reductase (A. M. Griffin, J. Gen. Virol. 1989. 70. 3085-3089, WO-A-90/02802) the genes present in the short unique sequence of the genome (U.sub.s) (M. A. Johnson et al., DNA Sequence--The Journal of Sequencing and Mapping 199S. Vol. 5. pp 191-194; K. Kongsuwan et al., Arch. Virol. 1995. 140. 27-39; K. Kongsuwan et al., Virus Research 1993. 29. 125-140; K. Kongsuwan et al., Virus Gene 1993. 7. 297-303; WO-A-92/03554; WO-A-95/00622). Web site: http://www.delphion.com/details?pn=US06153199__ •
Compositions and methods for the inhibition of MUC-5 mucin gene expression Inventor(s): Basbaum; Carol (San Francisco, CA), Gallup; Marianne (Greenbrae, CA), Gebremichael; Assefa (Berkeley, CA), Gensch; Erin (San Francisco, CA), Li; Daizong (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,136,539 Date filed: February 11, 1999 Abstract: The invention relates to methods for identifying inhibitors of mucin production, methods for inhibiting mucin production and methods for treating airway diseases, such as cystic fibrosis, chronic bronchitis, bronchial pneumonia and asthma. Compositions are provided for use in the method comprising reporter gene constructs which are inducible by mucomones. Excerpt(s): The present invention provides for methods of identifying compounds for treating medical conditions related to the inappropriate production of mucin, such as Pseudomonas infections of cystic fibrosis patients, bronchial pneumonia, chronic bronchitis and bronchial asthma. Mucins are a family of glycoproteins secreted from epithelial cells at many body surfaces, including the eyes, pancreatic ducts, gallbladder, prostate and mainly, respiratory, gastrointestinal and female reproductive tracts. Mucins are responsible for the viscoelastic properties of mucus. In the airways, mucin interacts with cilia to trap and clear pathogens and irritants. Bacterial infection of the airway epithelium is often accompanied by mucin overproduction. In addition, airway diseases such as chronic bronchitis, cystic fibrosis and asthma are characterized by mucus hypersecretion. Hypersecretion can overwhelm the ability of the cilia to function properly. Mucociliary impairment leads to airway mucus plugging which promotes chronic infection, airflow obstruction, and sometimes death. Nine mucin genes are known to be expressed in man: MUC 1, MUC 2, MUC 3, MUC 4, MUC 5AC, MUC 5B, MUC 6, MUC 7 and MUC 8 (Bobek, et al. (1993) J. Biol. Chem. 268:20563-9; Dusseyn, et
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al., (1997), J. Biol. Chem. 272:3168-78; Gendler, et al. (1991) Am. Rev.Resp. Dis. 144:S42S47; Gum, et al. (1989) J. Biol. Chem. 264:6480-6487; Gum, et al. (1990) Biochemical and Biophysical Research Communications 171:407-415; Lesuffleur, et al. (1995) J. Biol. Chem., 270:13665-13673; Meerzaman, et al. (1994) J. Biol. Chem. 269:12932-12939; Porchet, et al. (1991) Biochem. Biophys. Res. Comm. 175(2):414-422; Shankar, et al. (1994) Biochem. J., 300:295-298; Toribara, et al. (1997) J. Biol. Chem. 272:16398-403). Cysteinerich domains are considered to be typical of mucin sequences, having been reported in many mucins including MUC 2(Gum, et al. (1992), J. Biol. Chem. 267:21375-21383; Gum, et al. (1994), J. Biol. Chem. 269:2440-2446), MUC 5AC (Meerzaman, et al. (1994), J. Biol. Chem. 269:12932-12939), MUC 5B (Desseyn, et al. (1997) J. Biol. Chem. 272:3168-3178) and MUC 6 (Toribara, et al. (1997) J. Biol. Chem. 272:16398-16403) as well as in rat (Ohmori, et al. (1994) J. Biol. Chem. 269:17833-17840), pig (Eckhardt, et al. (1991) The Journal of Biological Chemistry, 266(15):9678-9686), cow (Bhargava, et al. (1990) Proc. Nat. Acad. Sci. U.S.A. 97:6798-6802) and frog (Probst, et al. (1990) Biochemistry 29:62406244) mucins. The cysteine-rich domains in mucins show varying degrees of similarity to the D-domains of von Willebrand factor (vWF). Web site: http://www.delphion.com/details?pn=US06136539__ •
Decongestant/expectorant compositions Inventor(s): D'Addio; Alexander D. (Piscataway, NJ), Dang; Phuong Grace (West Windsor, NJ) Assignee(s): Medpointe Healthcare Inc. (Somerset, NJ) Patent Number: 6,462,094 Date filed: August 22, 2001 Abstract: Compositions consisting essentially of phenylephrine tannate and guaifenesin which are effective when administered orally for the symptomatic relief of cough associated with respiratory tract conditions such as the common cold, bronchial asthma, acute and chronic bronchitis are disclosed. Excerpt(s): The invention relates to novel decongestant/expectorant compositions containing two essential ingredients phenylephrine tannate and guaifenesin. A considerable number of tannic acids occur in nature. Chemically, these acids are described as polymers of different hydroxybenzoic acids. Generally, when the term tannic acid is employed, as in the present case, the acid referred to is gallotannic acid. The internal ester of gallic acid also frequently referred to as tannin. Tannic acid consists of an amorphous powder, glistening scales, or spongy masses varying in color from yellowish-white to light brown. Tannic acid is very soluble in water or alcohol. Web site: http://www.delphion.com/details?pn=US06462094__
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Indole and tetrahydroisoquinoline containing Alpha-keto oxadiazoles as serine protease inhibitors Inventor(s): Gyorkos; Albert C. (Westminster, CO), Spruce; Lyle W. (Chula Vista, CA) Assignee(s): Cortech Inc. (Bedminster, NJ) Patent Number: 6,100,238 Date filed: June 3, 1998
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Abstract: The present invention relates to certain substituted oxadiazole nonpeptides, which are useful as inhibitors of human neutrophil elastase (HNE) for the treatment of HNE-mediated processes implicated in conditions such as adult respiratory distress syndrome, septic shock and multiple organ failure. A series of studies also have indicated the involvement HNE in myocardial ischemia-reperfusion injury, emphysema. HNE-mediated processes are implicated in other conditions such as arthritis, periodontal disease, glomerulonephritis, dermatitis, psoriasis, cystic fibrosis, chronic bronchitis, atherosclerosis, Alzheimer's disease, organ transplantation, corneal ulcers, and invasion behavior of malignant tumors. Excerpt(s): The present invention relates to certain substituted oxadiazole nonpeptides, which are useful as inhibitors of serine proteases. The serine proteases are a class of enzymes, which includes elastase, chymotrypsin, cathepsin G, trypsin and thrombin. These proteases have in common a catalytic triad consisting of Serine-195, Histidine-57 and Aspartic acid-102 (chymotrypsin numbering system). Human neutrophil elastase (HNE) is a proteolytic enzyme secreted by polymorphonuclear leukocytes (PMNs) in response to a variety of inflammatory stimuli. This release of HNE and its extracellular proteolytic activity are highly regulated and are normal, beneficial functions of PMNs. The degradative capacity of HNE, under normal circumstances, is modulated by relatively high plasma concentrations of.alpha.sub.1 -proteinase inhibitor (.alpha.sub.1 PI). However, stimulated PMNs produce a burst of active oxygen metabolites, some of which (hypochlorous acid for example) are capable of oxidizing a critical methionine residue in.alpha.sub.1 -PI. Oxidized.alpha.sub.1 -PI has been shown to have limited potency as an HNE inhibitor and it has been proposed that alteration of this protease/antiprotease balance permits HNE to perform its degradative functions in localized and controlled environments. Despite this balance of protease/antiprotease activity, there are several human disease states in which a breakdown of this control mechanism is implicated in the pathogenesis of the condition. Improper modulation of HNE activity has been suggested as a contributing factor in adult respiratory distress syndrome, septic shock and multiple organ failure. A series of studies also have indicated the involvement of PMNs and neutrophil elastase in myocardial ischemiareperfusion injury. Humans with below-normal levels of.alpha.sub.1 -PI have an increased probability of developing emphysema. HNE-mediated processes are implicated in other conditions such as arthritis, periodontal disease, glomerulonephritis, dermatitis, psoriasis, cystic fibrosis, chronic bronchitis, atherosclerosis, Alzheimer's disease, organ transplantation, corneal ulcers, and invasion behavior of malignant tumors. Web site: http://www.delphion.com/details?pn=US06100238__ •
Isoxazole derivatives to be used as phosphodiesterase VII inhibitors Inventor(s): Eggenweiler; Hans-Michael (Weiterstadt, DE), Gassen; Michael (Griesheim, DE), Jonas; Rochus (Darmstadt, DE), Welge; Thomas (Alsbach, DE), Wolf; Michael (Darmstadt, DE) Assignee(s): Merck Patentgesellschaft (Darmstadt, DE) Patent Number: 6,531,498 Date filed: May 3, 2002 Abstract: The invention relates to compounds of formula I and to their physiologically acceptable salts and solvates which act as phosphodiesterse VII inhibitors and are thus useful for the treatment of allergic disorders, asthma, chronic bronchitis, atopic
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dermatitis, psoriasis and other skin disorders, inflammatory disorders, autoimmune diseases, rheumatoid arthritis, multiple sclerosis, Crohn's disease, diabetes mellitus or ulcerative colitis, osteoporosis, transplant rejection reactions, cachexia, tumor growth, tumor metastases, sepsis, memory disturbances, atherosclerosis and AIDS. Excerpt(s): and their physiologically acceptable salts and/or solvates as phosphodiesterase VII inhibitors. The invention further relates to the use of the compounds of the formula I for producing a pharmaceutical for controlling allergic disorders, asthma, chronic bronchitis, atopic dermatitis, psoriasis and other skin disorders, inflammatory disorders, autoimmune diseases such as, for example, rheumatoid arthritis, multiple sclerosis, Crohn's disease, diabetes mellitus or ulcerative colitis, osteoporosis, transplant rejection reactions, cachexia, tumour growth or tumour metastases, sepsis, memory disturbances, atherosclerosis and AIDS. Compounds of the formula I are described by Bionet. Web site: http://www.delphion.com/details?pn=US06531498__ •
Isoxazoline compounds as inhibitors of TNF release Inventor(s): Cohan; Victoria Lee (East Lyme, CT), Kleinman; Edward Fox (Stonington, CT) Assignee(s): Pfizer Inc (New York, NY) Patent Number: 6,114,367 Date filed: November 6, 1998 Abstract: This invention relates to isoxazoline compounds which are inhibitors of tumor necrosis factor (TNF). The isoxazoline compounds are useful for inhibiting TNF in a mammal in need thereof and in the treatment or alleviation of inflammatory conditions or disease, including but not limited to rheumatoid arthritis, osteoarthritis, asthma, bronchitis, chronic obstructive airways disease, psoriasis, allergic rhinitis, dermatitis and inflammatory bowel disease, sepsis, septic shock, tuberculosis, graft versus host disease and cachexia associated with AIDS or cancer. This invention also relates to pharmaceutical compositions useful therefor comprising such compounds. Excerpt(s): This invention relates to a method of inhibiting production of TNF (tumor necrosis factor) in a mammal in need thereof which method comprises administering to said mammal an effective amount of a compound of the formula (I) (shown below) or a pharmaceutically acceptable salt thereof, which, as such are also useful in the treatment or alleviation of inflammatory conditions or disease including, but not limited to rheumatoid arthritis, osteoarthritis, asthma, bronchitis, chronic obstructive airways disease, psoriasis, allergic rhinitis, dermatitis and inflammatory bowel disease, sepsis, septic shock, tuberculosis, graft versus host disease and cachexia associated with AIDS or cancer; and this invention also relates to pharmaceutical compositions useful therefor. The compounds utilized in the present invention are disclosed and claimed in copending PCT Application Number PCT/IB94/00333 filed Oct. 26, 1994 and PCT Application Number PCT/IB94/00313 filed Oct. 12, 1994, both of which are assigned to the assignee hereof, and wherein said compounds are disclosed as having phosphodiesterase type IV (PDE.sub.IV) inhibiting activity. The teachings thereof are incorporated herein by reference. or R.sup.3 and R.sup.4 are taken together with the carbon atoms to which they are attached and form a carbocyclic ring having 4 to 7 carbon atoms. Web site: http://www.delphion.com/details?pn=US06114367__
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Method of treating bronchitis with uridine triphosphate and related compounds Inventor(s): Boucher; Richard C. (Chapel Hill, NC), Jacobus; Karla M. (Cary, NC), Rideout; Janet L. (Raleigh, NC), Shaffer; Christy L. (Chapel Hill, NC) Assignee(s): Inspire Pharmaceuticals, Inc. (Durham, NC) Patent Number: 6,159,952 Date filed: November 7, 1996 Abstract: A method of promoting clearance of retained mucous secretions in the bronchi, bronchioles and small terminal airways of a subject in need of such treatment is disclosed. The method comprises administering to the bronchi of the subject a uridine phosphate such as uridine 5'-triphosphate (UTP), or P.sup.1,P.sup.4 -di(uridine-5') tetraphosphate (U.sub.2 P.sub.4), an analog of UTP, or any other analog, in an amount effective to promote mucociliary clearance and/or cough clearance of retained fluid in the bronchi, bronchioles and small terminal airways. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: aerosol inhalation, any liquid suspension (including nasal drops or spray), oral form (liquid or pill), injected, intra-operative instillation or suppository form. Excerpt(s): This invention relates to a method of removing retained mucous secretions from the bronchi, bronchioles and small terminal airways of a subject by administering uridine triphosphate and other purinergic receptor agonists. Chronic bronchitis (CB) is excessive production of mucus in the bronchi accompanied by a recurrent cough that persists for at least three months of the year during at least two successive years. CB is the major non-asthmatic disease of the lung. This condition affects approximately 14 million Americans and is a major cause of death in the United States. Many different factors initiate CB, including cigarette smoking, environmental pollution, chronic infections and various genetic abnormalities. Of these factors, cigarette smoking is the most prevalent. Pathological changes in the lung consist of: (1) hypertrophy and hyperplasia of mucus-secreting glands in the bronchi, (2) increase in goblet cells, (3) disappearance or damage of cilia, and (4) chronic inflammatory changes and narrowing of small airways. Often, a bacterial or viral infection is present. Excess amounts of mucus are found in the airways and sometimes may occlude small bronchioles. Eventually, there may be scarring of the bronchial wall. Coughing is stimulated by retained mucus which cannot be adequately removed due to decreased cilia and lessened mucociliary clearance (K. Svartengen, et al., Exp. Lung Res.22, 555-76 (1996)). It is important that bronchitis patients clear retained mucus through coughing, however, often coughing is ineffective in adequately removing these secretions because the bronchitis patient cannot inspire deeply enough to cause air to flow distal to retained secretions. Current treatments for chronic bronchitis include antibiotic therapy, bronchodilators, anti-inflammatory agents and chest physiotherapy. These treatments are often palliative in nature rather than effective in treating and/or preventing the progression of this disease. While antibiotics are effective in treating exacerbations of bronchitis due to bacterial infections, the disadvantage of antibiotic therapy is that the patient may develop antibiotic resistance. There is increasing evidence that chronic bronchitis is caused by viral infections. The disadvantage of bronchodilators is that they sometimes have adverse cardiovascular side effects. As for anti-inflammatory agents, there is some controversy as to which stage in the progression of chronic bronchitis inflammation plays a role. None of these treatments have been successful in enhancing clearance of retained mucous secretions.
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Web site: http://www.delphion.com/details?pn=US06159952__ •
Methods for treatment of Emphysema using 13-cis retinoic acid Inventor(s): Belloni; Paula N (Half Moon Bay, CA) Assignee(s): Syntex (U.S.A.) LLC (Palo Alto, CA) Patent Number: 6,339,107 Date filed: August 2, 2000 Abstract: The current invention is directed to methods of treating or preventing emphysema, pharmaceutical compositions suitable for the treatment or prevention of emphysema and methods for delivering formulations into the lung of a mammal suffering from emphysema.More generally, the invention encompasses the use of 13-cisretinoic acid to treat or prevent certain chronic obstructive airway disorders, particularly chronic obstructive pulmonary disease including chronic bronchitis, emphysema and asthma in mammals, especially humans that smoke or smoked cigarettes. In another aspect, the present invention encompasses the use of pharmaceutical compositions of 13-cis-retinoic acid to treat emphysema. Moreover, the current invention encompasses the use of electrohydrodynamic aerosol devices, aerosol devices and nebulizers to deliver formulations of 13-cis-retinoic acid into the lung of a mammal suffering from emphysema. The invention also encompasses the systemic use as well as the local use of 13-cis-retinoic acid. In a another aspect the current invention encompasses a pharmaceutical composition for preventing emphysema in a human at risk of emphysema through administration of a amount of 13-cis-retinoic acid, or a pharmaceutically acceptable salt, hydrate, solvate, or pro-drug thereof in a pharmaceutically acceptable carrier, that is sufficient to prevent emphysema. Excerpt(s): The invention relates to methods of treating emphysema with 13-cis-retinoic acid, pharmaceutical compositions of 13-cis-retinoic acid useful in the treatment of emphysema and methods for delivering formulations of 13-cis-retinoic acid to the lung of a mammal suffering from emphysema. 13-cis-retinoic acid is also known as isotretinoin, AGN 190013, Neovitamin A acid, Ro-4-3780, 13-cis-.beta.-Retinoic acid and 13-cis-Vitamin A acid. 13-cis-retinoic acid is sold under the tradenames Accutane.RTM., Roaccutan.RTM. and Roaccutane.RTM. for the treatment of severe recalcitrant nodular acne (Physicians'Desk Reference 54.sup.th Ed., p. 2610, 2000; Peck et al., N. Eng. J Med.; Peck et al., U.S. Pat. No. 5,698,593). 13-cis-Retinoic acid has also been reported to be effective in treating psychotic illnesses such as schizophrenia (Straw, U.S. Pat. No. 4,808,630) and cancer of head, neck and lung (Tomas et al., Annals of Oncology, 1999, 10, 95; Benner et al., Seminars in Hematology, 1994, 31, 26). 13-cis -Retinoic acid is currently in clinical trials for treatment of these forms of cancer at a number of locations (e.g., University of Texas SW Medical Center, Dallas Tex.; University of Texas MD Anderson Cancer Center, Houston, Tex.; Department of Veteran Affairs Medical Center, Temple, Tex.). 13-cis-retinoic acid is a member of the retinoid class of compounds which are structural analogues of vitamin A and include both natural and synthetic compounds. Naturally occurring retinoid compounds such as all trans retinoic acid ("ATRA"), 9-cis retinoic acid, trans 3-4 didehydroretinoic acid, 4-oxo retinoic acid and retinol are pleiotrophic regulatory compounds that influence a large number of inflammatory, immune and structural cells. Web site: http://www.delphion.com/details?pn=US06339107__
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Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use Inventor(s): de Tejada; Inigo Saenz (Madrid, ES), Earl; Richard A. (Westford, MA), Garvey; David S. (Dover, MA), Khanapure; Subhash P. (Clinton, MA) Assignee(s): NitroMed, Inc. (Bedford, MA) Patent Number: 6,331,543 Date filed: September 1, 1999 Abstract: The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS). Excerpt(s): The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions comprising at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one phosphodiesterase inhibitor, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet
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obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, and glucoma, and diseases characterized by disorders of gut motility, such as irritable bowel syndrome (IBS). Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265-277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorgement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male, vasodilation of the cavernosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387-391 (1997). While there are obvious differences in the sexual response between males and females, one common aspect of the sexual response is the erectile response. The erectile response in both males and females is the result of engorgement of the erectile tissues of the genitalia with blood which is caused by the relaxation of smooth muscles in the arteries serving the genitalia. Web site: http://www.delphion.com/details?pn=US06331543__ •
Oregano-based therapeutic composition Inventor(s): Papaprodromou; Andreas D. (275 Norman Ave., Arcadia, CA 91007) Assignee(s): none reported Patent Number: 6,203,796 Date filed: July 8, 1999 Abstract: A therapeutic composition comprising oregano oil, laurel oil, and myrtle oil useful in alleviating pain and discomfort associated with arthritis, migraines, bronchitis, soft tissue injuries, muscle aches and pains and neck and back pains and strains in humans, as well as upper respiratory, joint and shin ailments in animals. Excerpt(s): Natural herbs have been used for centuries to alleviate the deleterious effects of numerous types of ailments, as well as the pain and discomfort associated with these ailments. More recently, patents have been granted to herbal remedies that disclose novel combinations of herbs purported to relieve the pain and other debilitating effects of numerous ailments and disorders. For instance, U.S. Pat. No. 1,298,407 teaches the use of a combination of natural herb oils and other ingredients for relief from catarrh, headache, toothache, sore throat, influenza, and colds. This herbal preparation purports to alleviate pain in the case of certain ailments. Another example of an herbal remedy is taught in U.S. Pat. No. 3,067,103. Here the use of a Gardenia florida seed extract was reported to have enhanced healing properties when applied to soft tissue injuries. Web site: http://www.delphion.com/details?pn=US06203796__
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Peptide tumor cell growth inhibitors Inventor(s): Hayashi; Shinichiro (Saga, JP), Miller; Edmund J. (Flint, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 6,110,889 Date filed: May 29, 1997 Abstract: Disclosed are peptide-based compositions and methods for inhibiting and modulating the actions of CXC intercrine molecules. The antileukinate peptides described inhibit IL-8, GRO and MIP2.beta. binding to neutrophils and neutrophil activation. The peptides are particularly advantageous as they inhibit IL-8-induced enzyme release at a 25 fold lower concentration than is required to inhibit chemotaxis, which makes them ideal for treating various inflammatory diseases and disorders including, amongst others, Adult Respiratory Distress Syndrome (ARDS), cystic fibrosis and chronic bronchitis. The invention further includes methods for inhibiting tumor cell growth by employing selected members of the disclosed group of peptides to inhibit.alpha.-chemokine binding to the tumor cell. Excerpt(s): The present invention relates generally to the field of cytokine actions and more particularly concerns methods and compositions for inhibiting and modulating the actions of CXC intercrine molecules. Disclosed are peptide compositions which inhibit interleukin 8 (IL-8) and, particularly, which preferentially inhibit IL-8-induced release of degradative enzymes by neutrophils. These compositions may be employed to treat various inflammatory diseases and disorders including the Adult Respiratory Distress Syndrome (ARDS) and cystic fibrosis. Recently, a second chemokine was found to be important for melanoma cell growth and metastasis in some melanoma cell lines. Schadendorf and colleagues determined that some melanoma cell lines tested secreted IL-8 (Schadendorf et al., 1993). Both of two IL-8 secreting cell lines studied in more detail were dependent on IL-8 for growth. Antisense oligonucleotides targeted against human IL-8 mRNA inhibited cell proliferation, colony formation in soft agar, and secretion of IL-8 into culture supernatants. In an analysis of 13 different human melanoma cell lines, it was shown that expression of IL-8 correlates with the metastatic potential of melanoma cells in BALB/c nude mice (Singh et al., 1994). Other studies further indicate a role of these chemokines in melanoma growth and tumorigenesis. Mintz and Silvers developed a method of producing melanomas by grafting skin from Tyr-SV40E transgenic mice which are highly susceptible to melanoma to Tyr-SV40E hosts of a low susceptibility of the same inbred strain (Mintz and Silvers, 1993). It was suggested that growth factors and cytokines known to be produced in wound repair may trigger the growth and malignant conversion of melanocytes. Nanney and colleague showed that MGSA/GRO.alpha. and its receptors are present in human bum wounds and may act as a mediator for wound repair (Nanney et al., 1995). MGSA/GRO.alpha. and I11-8 was induced by ultraviolet B radiation in human keratinocyte cell lines (Venner et al., 1995) IL-8 interacts with at least two distinct receptors on neutrophils (Holmes et al., 1991; Murphy and Tiffany, 1991). The receptors are coupled to GTP-binding proteins, allowing transmission of the IL-8 signal into the cell (Wu et al., 1993). While most of the members of the intercrine family, such as GRO and MIP2.beta., bind to one of the receptors, IL-8 binds to both of the IL-8 receptors (LaRosa et al., 1992; Cerretti et al., 1993). The three dimensional structure of IL-8 has been elucidated by NMR (Clore et al., 1990) and by X-ray crystallography (Clore and Gronenbom, 1992; Baldwin et al., 1991). A freely movable amino terminal end is followed by three beta pleated sheets and an alpha helix is located at the carboxyl-terminal end (Oppenheim et al., 1991). Several lines
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of evidence suggest that both the amino- and carboxyl-terminal ends are involved in binding to its receptors (Clore et al., 1990; Clark-Lewis et al., 1991; Moser et al., 1993). Web site: http://www.delphion.com/details?pn=US06110889__ •
Poultry vaccine Inventor(s): Cook; Jane Kathleen Alexandra (Cambs, GB) Assignee(s): Akzo Nobel N.V. (Arnhem, NL) Patent Number: 6,086,892 Date filed: March 26, 1998 Abstract: This invention relates to a novel infectious bronchitis virus (IBV) serotype and to attenuated IBV strains derived therefrom, and also to live or inactivated vaccines made using such IB virus. This invention also relates to a method for protecting poultry against IBV using these vaccines. Excerpt(s): The present invention relates to a new infectious bronchitis virus serotype, to attenuated infectious bronchitis virus strains derived from this new serotype and to a live vaccine, for use in immunizing poultry, which vaccine contains the attenuated strain of infectious bronchitis virus. The invention also relates to an inactivated vaccine containing either the new serotype which has been inactivated, or an inactivated attenuated strain derived therefrom. The invention is also concerned with a process for the preparation of live infectious bronchitis vaccines. Infectious bronchitis virus (IBV) is a member of the genus coronavirus of the family Coronaviridae. The virus is usually about 80-100 nm in size, being round with projecting 20 nm spikes. IBV is the causative agent of an acute, highly contagious disease in chickens of all ages, affecting the respiratory, reproductive and renal systems. Spackman and Cameron (Veterinary Record, (1983), 113, 354-355.) isolated IBV from pheasants with a history of respiratory signs and aberrant egg production. This disease problem in pheasants was successfully controlled by the use of oil-based inactivated IBV vaccine. Thus the term poultry, as used herein, is intended to embrace chickens, pheasants and any other domesticated bird serving as a source of eggs or meat and that are susceptible to infection by IBV. Web site: http://www.delphion.com/details?pn=US06086892__
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Pyrrolopyrrolone derivatives Inventor(s): Dowle; Michael Dennis (Stevenage, GB), Finch; Harry (Stevenage, GB), Harrison; Lee Andrew (Stevenage, GB), Inglis; Graham George Adam (Stevenage, GB), Johnson; Martin Redpath (Stevenage, GB), MacDonald; Simon John Fawcett (Stevenage, GB), Shah; Pritom (Stevenage, GB) Assignee(s): Glaxo Wellcome Inc. (Research Triangle Park, NC) Patent Number: 6,177,425 Date filed: May 5, 2000 Abstract: According to the invention there are provided Hexahydro-Pyrrolo[3,4b]pyrrol-2-one compounds of formula (1), (relative stereochemistry indicated), wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification. Compounds of formula (1) are useful inter alia in the treatment or chronic bronchitis.
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Excerpt(s): The present invention relates to therapeutically active bicyclic compounds, processes for their manufacture, pharmaceutical formulations containing them and their use in chemotherapy. In particular, we have found a group of novel bicyclic compounds which are effective in treating inflammatory diseases. Inflammation is a primary response to tissue injury or microbial invasion and is characterised by circulating leukocytes binding to and extravasation through vascular endothelium. Circulating leukocytes include neutrophils, eosinophils, basophils, monocytes and lymphocytes. Different forms of inflammation involve different types of infiltrating leukocytes. The inflammatory process can be triggered in a number of ways, including by infection, tissue damage and autoimmune reactions. As part of the inflammatory process, neutrophils move from the bloodstream into the tissue at the site of tissue lesion. The neutrophils contain large numbers of different intracellular granules and when activated at the site of inflammation the contents of these granules are secreted into the tissue. The different granules contain a variety of enzymes and other proteins, many of which have antibacterial properties. Web site: http://www.delphion.com/details?pn=US06177425__ •
Template associated NPY Y2-receptor agonists Inventor(s): Grouzmann; Eric (Chemin du Creux-de-Corsy 57, 1093 La Conversion Vaud, CH), Lacroix; Jean-Silvain (Chemin des Campanules 1, 1219 Aire Geneva, CH), Mutter; Manfred (Chemin de la Venoge 9, 1028 Preverenges Vaud, CH) Assignee(s): none reported Patent Number: 6,288,029 Date filed: January 14, 1999 Abstract: The present invention is directed to agonists of neuropeptide Y (NPY) or PYY that are formed by combining these peptides or a portion of these peptides with a template that promotes biologically active folds. Typically, templates consist of cyclized peptides containing one or more naphthyl ring structures. The agonists may be used in the treatment of diseases and conditions known to be responsive to NPY or PYY and, particularly in the treatment of asthma, rhinitis, and bronchitis. Excerpt(s): The present invention is directed to a new type of agonist that interacts preferentially with the neuropeptide Y (NPY) Y2 receptor. The agonist contains one or more peptides with sequences from the C-terminal end of neuropeptide Y (NPY) or peptide YY (PYY) bound to a template that promotes the correct folding of these peptides. In addition, the present invention is directed to methods for reducing airway resistance in bronchial patients by administering NPY, PYY, or agonists of these peptides. Neuropeptide Y (NPY) is an amidated peptide widely distributed in the central and peripheral nervous systems (Tatemoto, et al., Nature 296:659-660 (1982); Ekblad, et al., Regul. Peptides 8:225-235 (1984)). It is present in all sympathetic nerves innervating the cardiovascular system and is the most abundant peptide in the brain and the heart (Tatemoto, et al., Nature 296:659-660 (1982)). In addition, NPY is present in platelets (Ericsson, et al., Proc. Natl. Acad. Sci. U.S.A. 84:5587-5591 (1987)), the endothelium (Id.); the adrenal medulla (Allen, et al., J. Auton. Nerv. Sys. 9:559-566 (1983)); the pancreas (Jamal, et al., Endocrinology 129:3372-3380 (1991)); the kidney (Grouzmann, et al., Peptides 15 (8):1377-1382 (1994)); and the pituitary gland (Gehlert, et al., Peptides 15 (4):651-656 (1994)). Peptide YY (PYY) is a closely related peptide that has similar biological effects to NPY and which is found primarily in the gut. The biological actions of NPY and peptide YY are mediated by a number of G-protein coupled
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receptors termed Y1, Y2, Y3, Y4/PP and Y5 (Herzog, et al., Proc. Natl. Acad. Sci. U.S.A. 89:5794-5798 (1992)). Of these, the physiological effects associated with the Y1 and Y2 receptors are the best characterized. Exposure to a Y1 agonist causes an increase in blood pressure and potentiates post-synaptically the action of other vasoactive substances (Wahlestedt, et al., J. Pharmacol. Exp. Ther. 234:735-741 (1985)). In contrast, Y2 receptors are mainly located presynaptically and, upon stimulation, mediate the inhibition of neurotransmitter release (Westfall, et al., J. Cardiovasc. Pharmacol. 10:716722 (1987)). Web site: http://www.delphion.com/details?pn=US06288029__ •
Therapeutic agents for respiratory diseases Inventor(s): Hiki; Masato (Osaka, JP), Tanaka; Masaya (Kobe, JP) Assignee(s): Medion Research Laboratories (Hyogo, JP) Patent Number: 6,309,674 Date filed: November 19, 1999 Abstract: Prophylactic or therapeutic agents for respiratory diseases, allergic diseases, keratosis, and carcinomatous pain, containing Smilax china or a plant analogous thereto as the active ingredient. These agents can improve the condition and predisposition of acute and chronic respiratory diseases, such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, pan bronchiolitis and bronchiectasis, allergic diseases, such as atopic dermatitis, pollinosis, allergic rhinitis and allergic conjunctivitis, and keratosis, such as psoriasis, lichen, ichthyosis, furfur, and palmoplantar keratosis without side effects and at the same time can lower serum IgE level on an abnormally high level in a short period of time. After the symptom and predisposition have been improved, these agents can, even after suspension of administration, persistently lower the serum IgE level and in addition can inhibit the recurrence of the symptom. Excerpt(s): This application is a 371 of PCT/JP98/02237, filed May 21, 1998. The therapeutic agent for respiratory disease according to this invention relates to a prophylactic or therapeutic drug for respiratory diseases, a prophylactic or therapeutic drug for allergic diseases, a prophylactic or therapeutic drug for keratosis, a prophylactic or therapeutic drug for carcinomatous pain, a health food, a performance food, a cosmetic additive and a cosmetic product, which are capable of improving the symptom of, and the predisposition to, acute and chronic respiratory diseases, such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, pan bronchiolitis and bronchiectasis, allergic diseases, such as atopic dermatitis, pollinosis, allergic rhinitis and allergic conjunctivitis, and keratosis, such as psoriasis, lichen, ichthyosis, furfur, and palmoplantar keratosis without side effects and at the same time capable of lowering serum IgE level on an abnormally high level in a short period of time. After the symptom and predisposition have been improved, these agents can, even after suspension of administration, persistently lower the serum IgE level if it is still abnormally high and in addition can inhibit the recurrence of the symptom. Acute and chronic respiratory diseases such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, diffuse ordinary bronchiolitis and bronchiectasis are intractable diseases. The therapy of these diseases is generally a symptomatic treatment centered around temporary control of coughing with an antitussive or, in case respiratory distress intervenes, assisted respiration with a bronchodilator, although the treatment is not rewarding in cases of severe coughing. Moreover, bronchial asthma can be regarded as allergy and anti-allergics are also used for its prevention or therapy but
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the efficacy of such medication is not always reliable but even in patients with remission of the symptom, suspension of the administration results in recurrence of the symptoms. Adrenocortical hormones are administered in severe cases but, despite a certain rewarding effect they provide, sometimes cause intense side effects. Moreover, those, too, are symptomatic remedies. Thus, no drug is known of which recurrence of the symptom does not occur after suspension of administration. Health foods, for instance, are also available with claims to the effect that their intake leads to improvements in the patient's predisposition and a cure of diseases or control of symptoms but their efficacy is either not steadfast or has not been medically proven. Web site: http://www.delphion.com/details?pn=US06309674__ •
Therapeutic dinucleotide and derivatives Inventor(s): Boucher, Jr.; Richard C. (Chapel Hill, NC), Pendergast; William (Durham, NC), Picher; Maryse (Carrboro, NC), Rideout; Janet L. (Raleigh, NC), Stutts; M. Jackson (Chapel Hill, NC), Yerxa; Benjamin R. (Raleigh, NC) Assignee(s): Inspire Pharmaceuticals, Inc. (Durham, NC), University of North Carolina at Chapel Hill (Chapel Hill, NC) Patent Number: 6,323,187 Date filed: May 21, 1999 Abstract: The present invention relates to P.sup.1 -(cytidine 5'-)-P-(uridine 5')tetraphosphates and its salts, esters and amides, and formulations thereof which are highly stable and selective agonists of the P2Y.sub.2 and/or P2Y.sub.4 purinergic receptor. The compounds of the invention are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, primary ciliary dyskinesia, cystic fibrosis, as well as prevention of pneumonia due to immobility, and the induction of sputum and its expectoration. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis and otitis media. Excerpt(s): This invention relates to a method of enhancing clearance of secretions by increasing the hydration of retained mucus secretions, stimulating the production of mucins, and increasing ciliary beat frequency by administering P.sup.1 -(cytidine 5'-)P.sup.4 -(uridine 5'-)-tetraphosphate (CP.sub.4 U) or pharmaceutically acceptable esters, amides or salts thereof. Chronic obstructive pulmonary disease (COPD) affects 15 million patients in the U.S. and is the sixth leading cause of death. It is characterized by the retention of mucus secretions in the lungs which results in progressive lung dysfunction over time. Many patients diagnosed with COPD have a disorder called chronic bronchitis (CB), and 600,000 patients are hospitalized each year due to an acute exacerbation of CB. Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are other examples of lung disorders which assume a clinical profile similar to COPD. Ciliary dyskinesia, whether primary or secondary, results in retained secretions that can only be cleared by coughing. Most patients with COPD utilize coughing to help clear retained secretions because of impaired mucociliary clearance. Another disease state characterized by the accumulation of retained mucous secretions is sinusitis. Sinusitis is an inflammation of the paranasal sinuses typically associated with an upper respiratory infection. It can occur as either an acute or chronic condition. It is this country's most common health-care complaint, affecting an estimated 31 million people. (A. Moss and V. Parsons, National Center for Health Statistics, 1986: 66-7, DHHS Publication No. (PHS)86-1588 (1985)).
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Web site: http://www.delphion.com/details?pn=US06323187__
Patent Applications on Bronchitis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to bronchitis: •
Anti-inflammatory peptides derived from C-reactive protein Inventor(s): Fridkin, Matityahu; (Rehovot, IL), Yavin, Eran; (Rehovot, IL) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20030152564 Date filed: February 27, 2003 Abstract: A peptide corresponding to positions 62-71 of the sequence of human Creactive protein (CRP) of the formula: Glu.sub.62-Ile-Leu-Ile-Phe-Trp-S- er-Lys-AspIle.sub.71 and modifications thereof obtained by substitution, deletion, or addition of amino acids, amidation of the C-terminal or acylation of the N-terminal, are capable of inhibiting in vitro the enzymatic activity of human Leukocyte Elastase (hLE) and/or of human Cathepsin G (hCG) and can be used for the treatment of chronic inflammation conditions such as rheumatoid arthritis, pulmonary emphysema, cystic fibrosis, bronchitis, asthma and some acute respiratory distress syndrome. Excerpt(s): The present invention relates to synthetic peptides derived from the primary sequence of the acute phase reactant C-reactive protein (CRP), more particularly to a peptide corresponding to positions 62-71 of CRP and derivatives thereof, which peptides inhibit in vitro the enzymatic activities of human leukocyte elastase (hLE) and/or human leukocyte cathepsin G (hCG), two potent serine proteases associated with tissue damage occurring in the course of several chronic inflammatory conditions. The invention further relates to anti-inflammatory pharmaceutical compositions comprising said CRP-derived peptides. The following abbreviations will be used throughout the specification: CRP, C-reactive protein; hLE, human leukocyte elastase; hCG, human leukocyte cathepsin G; MeOSuc-AAPV-NA, methoxysuccinyl-Ala-Ala- Pro-Val-nitroanilide; Suc-AAPF-NA, succinyl-Ala-Ala-Pro-Phe-nitroanilide. C-reactive protein (CRP) is a plasma protein classified as a major acute phase reactant due to its dramatic accumulation in the blood stream during the inflammatory response. Within a relatively short period (24-48 hr) following tissue injury or certain traumatic events, the CRP blood concentration may rise 1000-fold over the normal level to as high as 1 mg/ml (Ballue and Kushner, 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Antitussive/expectorant compositions Inventor(s): D'Addio, Alexander D.; (Piscataway, NJ), Dang, Phuong Grace; (West Windsor, NJ) Correspondence: Carella, Byrne, Bain, Gilfillan, Cecchi,; Stewart & Olstein; 6 Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20030044461 Date filed: August 22, 2001 Abstract: Compositions consisting essentially of carbetapentane tannate and guaifenesin which are effective when administered orally for the symptomatic relief of cough associated with respiratory tract conditions such as the common cold, bronchial asthma, acute and chronic bronchitis are disclosed. Excerpt(s): A considerable number of tannic acids occur in nature. Chemically, these acids are described as polymers of different hydroxybenzoic acids. Generally, when the term tannic acid is employed, as in the present case, the acid referred to is gallotannic acid. The internal ester of gallic acid also frequently referred to as tannin. Tannic acid consists of an amorphous powder, glistening scales, or spongy masses varying in color from yellowish-white to light brown. Tannic acid is very soluble in water or alcohol. Tannic acids are usually obtained from glycosides which consist of several molecules of a tannic acid in combination with glucose. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Avian polynucleotide vaccine formula Inventor(s): Audonnet, Jean-Christophe; (Lyon, FR), Bouchardon, Annabelle; (Lyon, FR), Riviere, Michel; (Ecully, FR) Correspondence: William S. Frommer; Frommer Lawrence & Haug Llp; 745 Fifth Avenue; New York; NY; 10151; US Patent Application Number: 20020037292 Date filed: February 16, 2001 Abstract: The avian vaccine formula comprises at least three polynucleotide vaccine valencies each comprising a plasmid integrating, so as to express it in vivo in the host cells, a gene with one avian pathogen valency, these valencies being selected from the group consisting of Marek's disease virus, Newcastle disease virus, infectious bursal disease virus, infectious bronchitis virus, infectious anaemia virus, the plasmids comprising, for each valency, one or more of the genes selected from the group consisting of gB and gD for the Marek's disease virus, HN and F for the Newcastle disease virus, VP2 for the infectious bursal disease virus, S, M and N for the infectious bronchitis virus, C+NS1 for the infectious anaemia virus. Excerpt(s): The present invention relates to a vaccine formula allowing the vaccination of avian species, in particular chickens. It also relates to a corresponding method of vaccination. Associations of vaccines against a number of viruses responsible for pathologies in chicken have already been proposed in the past. The associations developed so far were prepared from inactivated vaccines or live vaccines. Their use poses problems of compatibility between valencies and of stability. It is indeed necessary to ensure both the compatibility between the different vaccine valencies, whether from the point of view of the different antigens used from the point of view of
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the formulations themselves. The problem of the conservation of such combined vaccines and also of their safety especially in the presence of an adjuvant also exists. These vaccines are in general quite expensive. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Beta2-adrenergic receptor agonists Inventor(s): Choi, Seok-Ki; (Palo Alto, CA), Griffin, John H.; (Atherton, CA), Moran, Edmund J.; (San Francisco, CA) Correspondence: Gerald F. Swiss; Burns Doane, Swecker & Mathis, L.L.P.; P.O.BOX 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020055651 Date filed: August 21, 2001 Abstract: Disclosed are multibinding compounds which are.beta.2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor. Excerpt(s): This application claims the benefit of U.S. patent application Ser. No. 60/088,466, filed Jun. 8, 1998; and U.S. patent application Ser. No. 60/092,938, filed Jul. 15, 1998; the disclosures of which are incorporated herein by reference in their entirety. This invention relates to novel multibinding compounds (agents) that are.beta.2 adrenergic receptor agonists and pharmaceutical compositions comprising such compounds. Accordingly, the multibinding compounds and pharmaceutical compositions of this invention are useful in the treatment and prevention of respiratory diseases such as asthma and chronic bronchitis. They are also useful in the treatment of nervous system injury and premature labor.sup.2 Strosberg, A. D. "Structure, Function, and Regulation of Adrenergic Receptors" Protein Sci. 2, 1198-1209 (1993 ). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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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
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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)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs Inventor(s): Boucher, Richard C. JR.; (Chapel Hill, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20020099023 Date filed: March 1, 2002 Abstract: Chronic obstructive airway diseases are treated by administering an osmotically active compound such as a salt, sugar, sugar alcohol, or organic osmolyte to the afflicted airway surface. The compound may be administered as a liquid or dry powder aerosol formulation. Diseases that can be treated by the method include cystic fibrosis, chronic bronchitis, and ciliary dyskinesia. The formulations of the invention can also be used in conjunction with other active agents such as bronchodilators, sodium channel blockers, antibiotics, enzymes, or purinoceptor agonists on airway surfaces.
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Excerpt(s): This application claims priority from U.S. Provisional Patent Application Serial No. 60/137,991 filed Jun. 7, 1999 and from U.S. Provisional Patent Application Serial No. 60/113,785 filed Dec. 22, 1998, which are incorporated herein in their entirety. airway surfaces. This invention relates to methods and compositions useful for hydrating airway surfaces. Chronic obstructive pulmonary diseases are characterized by the retention of mucous secretions in the lungs. Examples of such diseases include cystic fibrosis, chronic bronchitis, and primary or secondary ciliary dyskinesia. Such diseases affect approximately 15 million patients in the United States, and are the sixth leading cause of death. Other airway or pulmonary diseases characterized by the accumulation of retained mucous secretions include sinusitis (an inflammation of the paranasal sinuses associated with upper respiratory infection) and pneumonia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Devices for creating collateral channels in the lungs Inventor(s): Laufer, Michael D.; (Menlo Park, CA), Roschak, Ed; (Mountain View, CA), Tanaka, Don; (Saratoga, CA) Correspondence: Morrison & Foerster Llp; 755 Page Mill RD; Palo Alto; CA; 94304-1018; US Patent Application Number: 20020049370 Date filed: July 18, 2001 Abstract: The devices and methods disclosed herein are directed to altering gaseous flow within a lung to improve the expiration cycle of, for instance, an individual having Chronic Obstructive Pulmonary Disease. More particularly, these devices and methods produce and to maintain collateral openings or channels through the airway wall so that expired air is able to pass directly out of the lung tissue to facilitate both the exchange of oxygen ultimately into the blood and/or to decompress hyper-inflated lungs. The devices and methods also disclose locating and selecting a site for creation of a collateral opening.The invention is directed to methods and devices to altering gaseous flow within a lung to improve the expiration cycle of an individual, particularly individuals having Chronic Obstructive Pulmonary Disease (COPD). More particularly, methods and devices are disclosed to produce and to maintain collateral openings or channels th rough the airway wall so that expired air is able to pass directly out of the lung tissue to facilitate both the exchange of oxygen ultimately into the blood and/or to decompress hyper-inflated lungs.The term "Chronic Obstructive Pulmonary Disease" (COPD) is generally used to describe the disorders of emphysema and chronic bronchitis. Previously, COPD was also known as Chronic Obstructive Lung Disease (COLD), Chronic Airflow Obstruction (CAO), or Chronic Airflow Limitation (CAL). Some also consider certain types of asthma to fall under the definition of COPD. Emphysema is characterized by an enlargement of air spaces inside the lung. Hence, Emphysema is an anatomic definition and it can only be presumed in a living patient. Chronic bronchitis is characterized by excessive mucus production in the bronchial tree. Chronic bronchitis is a clinical definition and denotes those individuals who meet criteria defining the disease. It is not uncommon for an individual to suffer from both disorders. Excerpt(s): In 1995, the American Lung Association (ALA) estimated that between 15-16 million Americans suffered from COPD. The ALA estimated that COPD was the fourthranking cause of death in the U.S. The ALA estimates that the rates of emphysema is 7.6 per thousand population, and the rate for chronic bronchitis is 55.7 per thousand population. Those inflicted with COPD face disabilities due to the limited pulmonary
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functions. Usually, individuals afflicted by COPD also face loss in muscle strength and an inability to perform common daily activities. Often, those patients desiring treatment for COPD seek a physician at a point where the disease is advanced. Since the damage to the lungs is irreversible, there is little hope of recovery. Most times, the physician cannot reverse the effects of the disease but can only offer treatment and advice to halt the progression of the disease. To understand the detrimental effects of COPD, the workings of the lungs requires a cursory discussion. The primary function of the lungs is to permit the exchange of two gasses by removing carbon dioxide from venous blood and replacing it with oxygen. Thus, to facilitate this exchange, the lungs provide a blood gas interface. The oxygen and carbon dioxide move between the gas (air) and blood by diffusion. This diffusion is possible since the blood is delivered to one side of the bloodgas interface via small blood vessels (capillaries). The capillaries are wrapped around numerous air sacs called alveoli which function as the blood-gas interface. A typical human lung contains about 300 million alveoli. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Differentiation of avian infectious bronchitis virus serotypes Inventor(s): Jackwood, Mark W.; (Watkinsville, GA), Kwon, Hyuk Moo; (Athens, GA) Correspondence: Gwendolyn D. Spratt, ESQ.; Needle & Rosenberg, P.C.; The Candler Building, Suite 1200; 127 Peachtree Street, N.E.; Atlanta; GA; 30303-1811; US Patent Application Number: 20020160357 Date filed: April 9, 2001 Abstract: The present invention relates, in general, to the genetics of viruses. In particular, the present invention provides methods of distinguishing between serotypes of avian infectious bronchitis virus based on restriction fragment length polymorphisms derived from the region of the S1 gene of IBV, peptides derived from the restriction fragments, related primers for polymerase chain reaction, and certain restriction length polymorphism patterns. Excerpt(s): The present invention relates, in general, to the genetics of viruses. In particular, the present invention relates to methods of distinguishing between serotypes of avian infectious bronchitis virus based on restriction fragment length polymorphisms, peptides derived from the restriction fragments, related primers for polymerase chain reaction, and certain restriction fragment length polymorphism patterns. Infectious bronchitis virus (IBV), the prototype of the family Coronaviridae, is the etiological agent of infectious bronchitis (IB), an acute, highly contagious disease of the respiratory and urogenital tracts of chickens (21). In spite of the use of vaccines for the control of IB, the disease continues to be a problem in commercial poultry because some serotypes do not cross protect against antigenically unrelated serotypes including variant strains of the virus (12,20). Both the isolation and serotype identification of IBV field isolates are important because vaccines are selected based on the serotypes of field isolates in a given area. Identification of newly introduced IBV serotypes or variant strains of IBV in a geographical area can be used to modify vaccination programs in order to provide greater protection against the endemic serotypes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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In ovo protection against infectious bronchitis Inventor(s): Davelaar, Frans Gerrit; (Putten, NL), Jongsma, Berend; (Soest, NL), Weststrate, Marinus Wynand; (Weesp, NL) Correspondence: John F. Levis; American Home Products Corporation; Patent Law Department; One Campus Drive; Parsippany; NJ; 07054; US Patent Application Number: 20010046500 Date filed: February 2, 2001 Abstract: The present invention is directed to processes and compositions for protecting host animals (e.g., chickens) from exposure to virulent infectious bronchitis virus. In ovo administration of live, avirulent strains of IB at appropriate dosage levels on a per egg basis provides an effective and efficient vaccination having acceptable safety and efficacy features. Excerpt(s): The invention is directed to novel ways of providing in ovo protection against infectious bronchitis (hereinafter, "IB") in host animals such as chickens. More particularly, vaccines derived from traditional commercially-available IB vaccines have proven to be both safe and efficacious upon appropriate in ovo administration to host animals as described herein. IB is a highly infectious/transmissible respiratory disease that affects chickens of all ages. The disease of IB is caused by a virus of the coronavirus group. IB disease symptoms vary widely; however, reported effects include death, respiratory tract distress, depressed production, decreased peak production of eggs, abnormalities in the eggshells, diarrhea, and a nephrosis/nephritis syndrome. Undesired weight loss in young chicks and/or insufficient/low-quality production of eggs from laying flocks are commercially-significant adverse impacts of IB disease in chickens. Commercially-available vaccines for IB are not administered in ovo. Rather, they are administered post-hatch in a variety of formats. Briefly, such vaccines are typically administered by the labor-intensive methods of spraying (e.g., hand spray, knapsack spray, or automated spray equipment) or in drops (eye or nose). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Inhibition of mucin release from airway goblet cells by polycationic peptides Inventor(s): Kim, Kwang Chul; (Ellicott City, MD) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20010033827 Date filed: May 17, 2001 Abstract: Polycationic peptides have been shown to be effective inhibitors of mucin secretion. Inhibition of mucin secretion using these polycationic peptides may be an important tool in the treatment of diseases associated with mucin hypersecretion, including asthma, chronic bronchitis, cystic fibrosis, and bronchiectasis. Excerpt(s): Hypersecretion of mucin in the airways is associated with a variety of diseases, including asthma, chronic bronchitis, cystic fibrosis, and bronchiectasis. Effective measures for inhibiting mucin secretion in the airways would be useful to mitigate the deleterious effects associated with mucin hypersecretion. Effective inhibition of mucin secretion would also be useful in enhancing the delivery of therapeutic agents to the airways and via the airways. It has been discovered, according
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to this invention, that polycationic peptides inhibit mucin secretion from airway goblet cells. It has also been discovered that the inhibition of mucin secretion by polycationic peptides is accompanied by minimal cytotoxicity to cells of airways, thereby by indicating the suitability of polycationic peptides for use in animals, particularly humans, for the inhibition of mucin secretion. It has also been discovered that polycationic peptides can prevent S02 induced goblet cell metaplasia. It is contemplated as part of this invention that polycationic molecules, particularly polycationic peptides or peptide mimetics, may be employed to inhibit mucin secretion for a variety of therapeutic purposes. For example, the polycationic molecules may be administered to alleviate mucin hypersecretion, particularly in disease conditions associated with mucin hypersecretion. For example, the compositions of the invention may be administered to treat asthma, chronic bronchitis, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. As another example, the polycationic molecules may be administered to reduce mucin in the airways in order to facilitate the bioavailability of therapeutic agents targeted to the airways, such as, for example, bronchodialators. As another example, the polycationic molecules may be administered to reduce mucin in the airways, thereby minimizing airway impedance and facilitating therapeutic agent delivery to the alveoli or through the alveoli to the blood stream. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mammalian mucinase, its recombinant production, and its use in therapy or prophylaxis against diseases in which mucus is involved or infectious diseases Inventor(s): Aerts, Johannes Maria Franciscus Gerardus; (Abcoude, NL), Boot, Rolf Gabriel; (Amsterdam, NL) Correspondence: Trask, Britt & Rossa; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030087414 Date filed: November 2, 2001 Abstract: The invention provides a mammalian mucinase capable of hydrolyzing mucin. Said mucinase is among others suitable for counteracting diseases in which mucus is involved. Said diseases comprise cystic fibrosis, COPD, asthma, bronchitis, tuberculosis, tumours with altered mucus expression, and mucus-containing pathogens. The invention also provides a pharmaceutical composition comprising an effective amount of said mucinase and a method of therapeutic or prophylactic treatment of an individual against a disease in which mucus is involved. Methods for obtaining said mucinase are also herewith provided, as well as nucleic acids encoding (part of) said mucinase. In one aspect the invention provides a diagnostic kit comprising a mucinase, a mucinasespecific antibody, a mucinase-derived peptide and/or nucleic acid encoding (part of) said mucinase. Excerpt(s): The invention relates to the field of medicine. More specifically, the invention relates to therapeutic or prophylactic treatment of an individual against a disease in which mucus is involved and/or an infection disease. The invention also relates to the preparation of a mucinase suitable for said treatment. Mucins form part of the dynamic, interactive defensive system of mammals at mucosal surfaces in for example the gastrointestinal tract, the respiratory tract, and reproductive organs. Mucins are highly glycosylated proteins occurring either as secretory or membrane bound forms. They have a unique molecular structure and chemical properties. The polypeptide backbone (apomucin) is rich in hydroxy amino acids, serine and threonine, which together with glycine, alanine and proline comprise nearly 50% of total amino acid residues of the
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protein, and are present as tandemly repeated sequences. The threonine and serine residues are the targets of O-glycosylation machinery and the extent of glycosylation is such that carbohydrates account for 50-85% of the dry weight of mucins. Secretory mucins are the major constituents of mucus secretions, lining the epithelial cells of digestive, respiratory and reproductive tracts (Gendler et al, 1995, Gum 1995). They are capable of forming gels at very low concentration by forming long thread like polymers resulting from the formation of disulphide linkages between monomers and intramolecular interactions of sugar side chains. Membrane bound mucins are present on the surface of various cell types and, unlike secretory mucins, do not form oligomers and are hence smaller in size than their secretory counterparts (Gendler et al, 1995, Gum 1995). The membrane bound mucins also have O-glycosylated serine and threonine rich regions, but they lack tandem repeat sequences. The primary function of secretory mucins is to provide protection to the apical epithelial cell layers in digestive, respiratory and urinogenital tracts against environmental factors like acidic pH, hydrolytic enzymes and pathogens. The cell surface mucins, in addition to their protective role, have shielding effect on various surface receptors, thereby helping in the regulation of their activity (Strous and Dekker 1992). So far, twelve human mucin genes have been identified designated as MUC1-4, MUC5AC, MUC5B, MUC6-9, and MUC1112 (Gendler et al, 1995, Gum 1995, Gum et al 1990, Lan et al 1990, Moniaux et al 1999, Shankar et al 1997, Williams et al 1999). They can be divided into secreted and membrane-associated forms each with characteristic protein domains and tissue specific glycosylation. Eight human mucin genes have been well characterized: MUC2, MUC5AC, MUC5B, MUC6 map to 11p15.5 and encode secretory gel forming mucins while MUC1, MUC3, MUC4, MUC7 are scattered on different chromosomes and encode membrane-bound or secreted mucins. Historically, purified mucins have been identified by their amino and carbohydrate composition consisting of a high percentage of serine, threonine, proline, alanine, glycine, and a large proportion of O-linked oligosaccharides (up to 80% of the total mass). Biosynthetic pathways have been described for the secreted and membrane-associated mucins and their eventual degradation and turnover. Mucins are present at all mucosal surfaces throughout the body in typical combinations and relate to the demands of organ function. Patterns of MUC gene expression with gastrointestinal site specific glycosylation are clearly important but are not yet well defined. The mucosal surface throughout the gastrointestinal tract must resist the aggressive elements from the external environment present in the diet and encountered during normal function. This defensive system is based on fundamental characteristics shared with the barrier found at other mucosal surfaces. The stable protective barrier enabling exchange between the epithelial cells of the gut lumen for the purposes of nutrition and protection is made up of a layer of secreted mucus and a cellsurface membrane glycocalyx. The mucus defensive barrier forms the first line of defence to the external environment and contains both innate and adaptive immune elements. Mucins are present at all mucosal surfaces throughout the body. The specific functional requirements for mucus at each site are reflected in the appearance of different mucins in the cells at different sites in the body. The main population of specially adapted cells producing secreted mucins are the goblet cells. The proportion of goblet cells increases through the gastrointestinal tract (GI tract) with maximal numbers in the rectum. Goblet cells in the respiratory tract are present in the trachea, and to a lesser extent in the bronchi. They are rarely found in bronchioles less than 1 mm in diameter (Jeffery et al 1992). Mucins have a tissue specific glycosylation at each site in the gastrointestinal tract. As carbohydrate constitutes the major part of all mature mucins and is represented by vast array of different oligosaccharide structures the potential for multiple functions related to bulk carbohydrate or individual structures must be examined. Most of the oligosaccharides in mucins are attached by O-links.
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However, a much smaller number of N-linked chains are also present, linked to asparagine residues in the mucin polypeptide through an N-glycosidic bond to Nacetyl-D-glucosamine. N-linked oligosaccharides contain a branched trimannosylchitobiose pentasaccharide core attached to the peptide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and compositions for enhancing pulmonary function and treating pulmonary disorders Inventor(s): Hite, Robert Duncan; (Winston-Salem, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20010038825 Date filed: February 5, 2001 Abstract: Pulmonary function may be increased and pulmonary disorders treated by administering pharmaceutical formulations consisting essentially of phosphatidyl glycerol (PG) and a pharmaceutically acceptable carrier. Pulmonary disorders that may be treated by these methods and formulations include respiratory distress syndrome, asthma, and chronic bronchitis. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/180,388, filed Feb. 4, 2000, which is incorporated herein by reference in its entirety. This invention relates to methods and compositions that are useful in enhancing pulmonary function generally, and in treating pulmonary disorders. Naturallyoccurring pulmonary surfactant (PS) lines the alveolar epithelium of mammalian lungs, and is a complex mixture of lipids and proteins. PS promotes the formation of a monolayer at the alveolar air-water interface and, by reducing the surface tension, prevents collapse of the alveolus during expiration. Natural PS contains phospholipids, certain neutral lipids, and proteins, with lipids making up 80% of the composition. The lipid component is composed mainly of dipalmitoyl phosphatidylycholine (dispalmitoyl lecithin), phosphatidyl glycerol, phosphatidylethanolamine, triglycerides cholesterol and cholesterol esters. The protein components of surfactant required for full surfactant properties include a family of apoproteins. The presence of a number of these apoproteins has been shown to enhance the rate of surface-film formation (see, e.g., Whitseft et al., Pediatr. Res., 20, 460 (1986); Avery et al., New Engl. J. Med., 315, 825 (1986)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of detecting inflammatory lung disorders Inventor(s): Rastelli, Luca; (Guilford, CT), Smithson, Glennda; (Branford, CT) Correspondence: Ivor R. Elrifi; Mintz, Levin, Cohn, Ferris,; Glovsky And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20020115626 Date filed: May 25, 2001 Abstract: Disclosed are methods of detecting and treating inflammatory lung disorders, such as emphysema, asthma bronchitis or allergy. Also disclosed are methods of identifying agents for treating inflammatory lung disorders.
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Excerpt(s): This application claims priority from U.S. Ser. No. 60/207,104, filed May 5, 2000 which is incorporated by reference in its entirety. The invention relates to methods of detecting inflammatory lung disorders. Antileukoproteases, also known as secretory leukocyte protease inhibitors, are a class of acid-stable proteinase inhibitors with strong affinity for trypsin and chymotrypsin as well as for neutrophil lysosomal elastase and cathepsin G. Antileukoproteases are present in mucous fluids such as seminal plasma, cervical mucus, bronchial and nasal secretions, and tears. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of preventing respiratory infections Inventor(s): Rezakhany, Saeed; (San Jose, CA) Correspondence: Saeed Rezakhany; 6933 Melvin DR; San Jose; CA; 95129; US Patent Application Number: 20030215533 Date filed: April 10, 2003 Abstract: A method is presented for prevention of various respiratory infections which can be caused by one or more pathogens (bacteria, viruses, and fungi) including, but not limited to, those causing the various forms of upper respiratory tract infection (common cold), influenza, bronchitis, laryngitis, etc. in human being, by using a non-toxic, easily accessible to public "effective formula" to attack the newly activated or the newly invading pathogen and rendering it ineffective. If the infection has already fully taken effect, the present method helps reduce the symptoms of the infection (illness) and its duration by preventing occurrence of secondary infections. This method may also be applied to other mammals. Excerpt(s): This application claims benefit of provisional application No. 60/371,882, filed Apr. 11, 2002, the entire disclosure of which is considered to be part of the disclosure of this application and is hereby incorporated by reference. Respiratory infections, particularly upper respiratory tract infections are very common and cause substantial suffering and hundreds of millions of dollars of economic loss every year. The majority of the pathogens contributing to upper respiratory tract infections are spread through air and through touching of the infected surfaces and then touching one's eyes or nose. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treatment Inventor(s): Henkel, Timothy John; (King of Prussia, PA) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020137751 Date filed: September 17, 2001 Abstract: A method of reducing the recurrences of acute exacerbations of chronic bronchitis (AECB) in a patient in need thereof comprising administering a therapeutically effective amount of gemifloxacin, or a pharmaceutically acceptable salt thereof.
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Excerpt(s): The present invention relates to the use of gemifloxacin for reducing the recurrences and/or reducing the severity of recurrences of acute exacerbations of chronic bronchitis (AECB). Patients with chronic bronchitis frequently experience episodes of exacerbation, characterised by increased cough, increased sputum volume and purulence, and respiratory distress. Annual death rates from chronic bronchitis and its exacerbations in various countries, range from approximately 20 to 80 deaths per 100,000 males aged from 55 to 65 years. The total direct medical costs of treating AECB have been estimated as at least.English Pound.396 million in the United Kingdom (UK) (1992/3) and up to $2.3 billion in the USA (1995/6). Patients who are hospitalised account for at least 67% of all costs. AECB is also responsible for a significant loss of working days, 1.54 million, and restricted activity days, 3.63 million, in the USA (1994). Patient well-being and quality of life may also be expected to be affected by AECB. The social, medical and economic consequences of AECB are thus considerable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods, compositions and modes of delivery for the treatment of emphysema using 13-cis-retinoic acid Inventor(s): Belloni, Paula N.; (Half Moon Bay, CA) Correspondence: Pennie & Edmonds, Llp; 1155 Avenue OF The Americas; New York; NY; 10036-2711; US Patent Application Number: 20020049252 Date filed: September 26, 2001 Abstract: The current invention is directed to methods of treating or preventing emphysema, pharmaceutical compositions suitable for the treatment or prevention of emphysema and methods for delivering formulations into the lung of a mammal suffering from emphysema.More generally, the invention encompasses the use of 13-cisretinoic acid to treat or prevent certain chronic obstructive airway disorders, particularly chronic obstructive pulmonary disease including chronic bronchitis, emphysema and asthma in mammals, especially humans that smoke or smoked cigarettes. In another aspect, the present invention encompasses the use of pharmaceutical compositions of 13-cis-retinoic acid to treat emphysema. Moreover, the current invention encompasses the use of electrohydrodynamic aerosol devices, aerosol devices and nebulizers to deliver formulations of 13-cis-retinoic acid into the lung of a mammal suffering from emphysema. The invention also encompasses the systemic use as well as the local use of 13-cis-retinoic acid. In a another aspect the current invention encompasses a pharmaceutical composition for preventing emphysema in a human at risk of emphysema through administration of a amount of 13-cis-retinoic acid, or a pharmaceutically acceptable salt, hydrate, solvate, or pro-drug thereof in a pharmaceutically acceptable carrier, that is sufficient to prevent emphysema. Excerpt(s): The invention relates to methods of treating emphysema with 13-cis-retinoic acid, pharmaceutical compositions of 13-cis-retinoic acid useful in the treatment of emphysema and methods for delivering formulations of 13-cis-retinoic acid to the lung of a mammal suffering from emphysema. 13-cis-retinoic acid is also known as isotretinoin, AGN 190013, Neovitamin A acid, Ro-4-3780, 13-cis-.beta.-Retinoic acid and 13-cis-Vitamin A acid. 13-cis-retinoic acid is sold under the tradenames Accutane.RTM., Roaccutan.RTM. and Roaccutane.RTM. for the treatment of severe recalcitrant nodular acne (Physicians' Desk Reference 54.sup.th Ed., p. 2610, 2000; Peck et al., N. Eng. J. Med.; Peck et al., U.S. Pat. No. 5,698,593). 13-cis-Retinoic acid has also been reported to be
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effective in treating psychotic illnesses such as schizophrenia (Straw, U.S. Pat. No. 4,808,630) and cancer of head, neck and lung (Tomas et al., Annals of Oncology, 1999, 10, 95; Benner et al., Seminars in Hematology, 1994, 31, 26). 13-cis-Retinoic acid is currently in clinical trials for treatment of these forms of cancer at a number of locations (e.g., University of Texas SW Medical Center, Dallas Tex.; University of Texas MD Anderson Cancer Center, Houston, Tex.; Department of Veteran Affairs Medical Center, Temple, Tex.). 13-cis-retinoic acid is a member of the retinoid class of compounds which are structural analogues of vitamin A and include both natural and synthetic compounds. Naturally occurring retinoid compounds such as all trans retinoic acid ("ATRA"), 9-cisretinoic acid, trans 3-4 didehydroretinoic acid, 4-oxo retinoic acid and retinol are pleiotrophic regulatory compounds that influence a large number of inflammatory, immune and structural cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mucin synthesis inhibitors Inventor(s): Jones, Steve; (West Chester, PA), Levitt, Roy C.; (Ambler, PA), McLane, Mike; (Lansdale, PA), Nicolaides, Nicholas C.; (Media, PA), Zhou, Yuhong; (Dreshler, PA) Correspondence: Morgan, Lewis & Bockius; 1800 M Street NW; Washington; DC; 200365869; US Patent Application Number: 20010041685 Date filed: January 31, 2001 Abstract: The claimed invention relates to methods of modulating mucin synthesis and the therapeutic application of compounds in controlling mucin over-production associated with diseases such as chronic obstructive pulmonary diseases (COPD) including asthma and chronic bronchitis, inflammatory lung diseases, cystic fibrosis and acute or chronic respiratory infectious diseases. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/179,127, filed on Jan. 31, 2000, Provisional Application No. 60/193,111, filed on Mar. 30, 2000, Provisional Application No. 60/230,783, filed Sep. 7, 2000, Provisional Application No. 60/______ filed Oct. 23, 2000 and Provisional Application No. 60/______ filed Nov. 20, 2000 all of which are herein incorporated by reference in their entirety. All of the above referenced applications are entitled "Mucin Synthesis Inhibitors" and the inventors are Yuhong Zhou, Roy C. Levitt, Nicholas C. Nicolaides, Steve Jones, and Mike McLane. This invention is also related to the subject matter of U.S. patent application Ser. No. 08/702,110, filed on Aug. 23, 1996, issued on Mar. 14, 2000, as U.S. Pat. No. 6,037,149 and is related to U.S. patent application Ser. No. 09/325,571, filed on Jun. 9, 1999 and U.S. Pat. No. 5,908,839 issued Jun. 1, 1999 all of which are all herein incorporated by reference in their entirety. In addition, this application is related to U.S. patent application Ser. No. 08/980,872, filed Dec. 1, 1997, which is herein incorporated by reference in its entirety. This invention relates to methods of modulating mucin synthesis and the therapeutic application of compounds in controlling mucin over-production associated with diseases such as asthma, chronic bronchitis, inflammatory lung diseases, cystic fibrosis and acute or chronic respiratory infectious diseases as well as chronic obstructive pulmonary diseases (COPD). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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New pharmaceutical compositions Inventor(s): Lang, Steffen; (Reinach, CH), Liechti, Kurt; (Oberwil, CH) Correspondence: Thomas Hoxie; Novartis Corporation; Patent And Trademark Dept; 564 Morris Avenue; Summit; NJ; 079011027 Patent Application Number: 20020156099 Date filed: April 10, 2002 Abstract: Spontaneously dispersible pharmaceutical compositions comprising a piperidine, e.g. 1-acyl-piperidine Substance P Antagonist and its use in the treatment of CNS disorders, e.g. depression and social phobia, and respiratory diseases, e.g. asthma and chronic bronchitis. Excerpt(s): The present invention relates to novel pharmaceutical compositions in which the active agent is a piperidine substance P antagonist, in particular a N-benzoyl-2benzyl-4-(azanaphthloyl-amino) piperidine, useful for treatment and prevention of e.g. central nervous system disorders, e.g. depression, social phobia, or respiratory diseases, e.g. asthma and chronic bronchitis. 1-Acylpiperidine substance P antagonists are a class of compounds described e.g. in published European patent EP 0532456B1, the contents of which publication is incorporated herein by reference. Similarly, N-benzoyl-2-benzyl4-(azanaphthoyl-amino) piperidines and their activity as Substance P Antagonists are described in published European patent application EP 0707006A, the contents of which application is incorporated herein by reference. Piperidine substance P antagonists, such as disclosed in EP 0532456B1 and EP 0707006A, present highly specific difficulties in relation to administration generally and galenic compositions in particular, including in particular problems of drug bioavailability and variability in inter- and intra-patient dose response, necessitating development of a non-conventional dosage form. In accordance with the present invention it has now surprisingly been found that stable pharmaceutical compositions with Piperidine substance P antagonists, having particularly interesting bioavailability characteristics and reduced variability in interand intra-subject bioavailability parameters, are obtainable. These novel compositions have been found to meet or substantially reduce the difficulties encountered previously. It has been shown that the compositions in accordance with the present invention may enable effective dosaging with concomitant enhancement as well as reduced variability of resorption/bioavailability levels for and between individual patients. Thus, the invention may achieve effective therapy with tolerable dosage levels of such Piperidine substance P antagonists, and may permit closer standardization and optimization of daily dosage requirements for each individual. Consequently, occurrence of potential undesirable side-effects is diminished and overall cost of therapy may be reduced. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel substituted 4-(1H-benzimidazol-2-yl) [1,4]diazepanes useful for the treatment of allergic diseases Inventor(s): Le, Tieu-Binh; (Bridgewater, NJ), Maynard, George D.; (Clinton, CT) Correspondence: Aventis Pharmaceuticals INC.; Patent Department; Route #202-206, Mail Code: Emc-g1; P.O. Box 6800; Bridgewater; NJ; 08807-0800; US Patent Application Number: 20010034343 Date filed: December 18, 2000
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Abstract: The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives of formula 1and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/513,847, filed Oct. 29, 1997, now allowed, which is a continuation-in-part of U.S. application Ser. No. 08/736,411, filed Oct. 24, 1996, now abandoned, which claims the benefit of U.S. Provisional application Ser. No. 60/070,907, filed Dec. 20, 1995. The present invention relates to novel substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives (herein referred to as a compound or compounds of formula (1)) and their use as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of asthma; bronchitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; allergic rhinitis, including seasonal rhinitis and sinusitis; allergies; and emesis. The compounds of the present invention are useful in their pharmacological activities, such as histamine receptor antagonism and tachykinin receptor antagonism. Antagonism of histamine responses can be elicited through blocking of histamine receptors. Antagonism of tachykinin responses can be elicited through blocking of tachykinin receptors. One object of the present invention is to provide new and useful antagonists of histamine. A further object of the present invention is to provide new and useful antagonists of tachykinins. A particular object of the present invention are those compounds that exhibit both histamine and tachykinin receptor antagonism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pyrimidine carboxamides useful as inhibitors of pde4 isozymes Inventor(s): Chambers, Robert James; (Mystic, CT), Magee, Thomas Victor; (Mystic, CT), Marfat, Anthony; (Mystic, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030144300 Date filed: July 24, 2002 Abstract: Compounds of formula (1.0.0) are described, as well as the usefulness of a pharmaceutical composition for treating inflammatory, respiratory and allergic diseases and conditions, especially asthma; chronic obstructive pulmonary disease (COPD) including chronic bronchitis, emphysema, and bronchiectasis; chronic rhinitis; and chronic sinusitis. Excerpt(s): Reference is made to copending International application and US application based thereon, Serial No. PCT/IB98/00315, both filed Mar. 10, 1998 (Attorney Docket No. PC9762A), and published as WO 98/45268 on Oct. 15, 1998; claiming priority from application Ser. No. 60/043,403 filed Apr. 4, 1997 (Attorney Docket No. PC9762), now abandoned; which discloses nicotinamide derivatives having biological activity as inhibitors of the PDE4 isozyme, and thus useful in the treatment of inflammatory, respiratory and allergic diseases and conditions. Nothing that is disclosed in the abovementioned applications would teach the person of ordinary skill in the pertinent art the novel compounds of the present invention or their unexpectedly high level of inhibitory
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activity for the PDE4 isozyme. Reference is also made to copending application Ser. No. 09/345,185 filed Jun. 30, 1999 (Attorney Docket No. PC10096A); claiming priority from application Ser. No. 60/105,120 filed Oct. 21, 1998 (Attorney Docket No. PC10096), which discloses compounds and processes for preparing N-substituted nicotinamide derivatives. However, the disclosed compounds and processes are not the same as those of the present invention. Reference is further made to copending applications filed of even date with the instant application, Attorney Docket Nos. PC10523; PC10546; PC10657; PC10690; and PC10691, which involve other classes of nicotinamide derivatives useful as selective inhibitors of the PDE4 isozyme. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Therapeutic morpholino-substituted compounds Inventor(s): Jackson, Shaun; (Melbourne, AU), Kenche, Vijaya; (Melbourne, AU), Parbaharan, Hishani; (Melbourne, AU), Roberton, Alan D.; (Melbourne, AU), Thompson, Phil; (Melbourne, AU), Yap, Cindy; (Melbourne, AU) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030216389 Date filed: November 8, 2002 Abstract: Morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-kinase, an enzyme that regulates plateletadhesion processes. As a consequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. The compounds claimed are represented by formula (I), (II) and (III). PI 3-kinase generates 3-phosphorylated PI second messengers which stimulate platelet adhesion under blood-flow conditions. Because platelet adhesion is a necessary step in the formation of a thrombus, inhibition by these compounds of PI 3-kinase under such conditions inhibits or prevents thrombus formation. The compounds are useful in treating PI 3-kinase-dependent conditions including cardiovascular diseases such as coronary artery occlusion, stroke, acute coronary syndrome, acute myocardial infarction, vascular restenosis, atherosclerosis, and unstable angina; respiratory diseases such as asthma, chronic obstructive pulmonary diseases (COPD), and bronchitis; inflammatory disorders; neoplasms including cancers such as glioma, prostate cancer, small cell lung cancer, and breast cancer, and diseases linked to disordered white blood cell function, such as autoimmune and inflammatory diseases. 1 Excerpt(s): The present invention is broadly concerned with anti-thrombotic morpholino-substituted compounds and corresponding methods of use. More particularly, the present invention relates to morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives which inhibit the enzyme phosphoinositide (PI) 3-kinase, and which are useful in treating PI 3-kinase-dependent conditions, including cardiovascular diseases, respiratory diseases, inflammatory disorders, neoplasms such as cancers, and diseases linked to disordered white blood cell function. Cell-adhesion interactions are crucial for a broad range of physiological processes, including inflammation, immunity, and hemostasis. Platelets are specialized adhesive cells which play a fundamental role in the hemostatic process. Upon vascular injury, platelets adhere to specific subendothelial adhesive proteins, such as von Willebrand factor (vWF). The binding of vWF to its specific receptor on the platelet surface, glycoprotein (GP) Ib/V/IX, induces platelet activation and cytoskeletal reorganization.
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These cytoskeletal changes result in filopodial extension and the formation of lamellipodial sheets, which are essential processes for platelet spreading and the formation of the primary hemostatic platelet plug. An exaggerated platelet adhesion response at sites of atherosclerotic plaque rupture commonly leads to the formation of vaso-occlusive platelet thrombi. The formation of these thrombi in the coronary or cerebral circulation leads to heart attacks and strokes, respectively, which combined represent the leading causes of death in the industrialized world. Platelet thrombus formation also leads to a number of other clinical states including unstable angina, sudden death, transient ischemic attacks, amaurosis fugax, and acute ischemia of limbs and internal organs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
THERAPEUTICALLY ACTIVE COMPOUNDS BASED ON INDAZOLE BIOISOSTERE REPLACEMENT OF CATECHOL IN PDE4 INHIBITORS Inventor(s): MARFAT, ANTHONY; (MYSTIC, CT) Correspondence: Paul H Ginsburg; Pfizer Inc; 235 East 42nd Street; 20th Floor; New York; NY; 10017-5755; US Patent Application Number: 20020058687 Date filed: September 20, 1999 Abstract: Therapeutically active compositions of matter are described which are useful for treating or preventing diseases and conditions comprising inflammatory diseases including joint inflammation, Crohn's disease, and inflammatory bowel disease; respiratory diseases such as chronic obstructive pulmonary disease (COPD) including asthma, chronic bronchitis, and pulmonary emphysema; infectious diseases including endotoxic shock and toxic shock syndrome; immune diseases including systemic lupus erythematosis and psoriasis; and other diseases including bone resorption diseases and reperfusion injury; wherein said composition of matter comprises a compound which is an inhibitor of phosphodiesterase isozyme 4 (PDE4) and wherein an indazole is one essential component of said compound's overall chemical structure, and wherein said indazole constitutes a bioisosteric replacement of a catechol component or functional derivative thereof in a known compound having the same said therapeutic activity and the same remaining said components of its overall chemical structure. Included are compounds of Formula (IA) or (IB), wherein R.sup.2.sub.a and R.sup.2.sub.b are independently selected from the group consisting essentially of hydrogen and hereinafter recited substituents, provided that one, but not both of R.sup.2.sub.a and R.sup.2.sub.b must be independently selected as hydrogen, wherein said substituents comprise moieties including the following: (IC), (ID), (IE), (IF), (ILA), (ILB), (IIC), (IID), (IIE), (IIF), (IIG), (IIH), (III), (IIIA), (IIIB), (IIIC), (IIID), (IIIE), (IIIF), (IIIG), (IIIH), (IIII), (IIIJ), (IIIK), (IIIL), (IIIM), (IIIN), (IIIO), (IIIP), (IIIR), (IIIS), (IIIT), (IV), (VA), (VB), (VC), (VD), (VE.sub.a), (VE), (VF), (VG), (VH), (VI), (VJ), (VK), (VL), (VM). 1 Excerpt(s): The present invention is in the field of compositions of matter, and pharmaceutical compositions and methods of treatment utilizing one or more of said compositions of matter as the active ingredient and the active agent with respect thereto, wherein said composition of matter comprises an indazole as an essential feature of its overall chemical structure, said indazole constituting a bioisosteric replacement of a catechol or functional derivative thereof. The catechol-containing as well as the indazole-based compositions of matter have biological activity as selective inhibitors of phosphodiesterase (PDE) type IV and the production of tumor necrosis factor (TNF),
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and as such are useful in the treatment of asthma, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, dermatitis, Crohn's disease, arthritis, and other inflammatory diseases, AIDS, septic shock and other diseases involving the production of TNF. This invention also relates to a method of using such compounds in the treatment of the foregoing diseases in mammals, especially humans, and to pharmaceutical compositions containing such compounds. Since the recognition that cyclic adenosine phosphate (AMP) is an intracellular second messenger, E. W. Sutherland, and T. W. Rall, Pharmacol. Rev., 12, 265, (1960), inhibition of the phosphodiesterases has been a target for modulation and, accordingly, therapeutic intervention in a range of disease processes. More recently, distinct classes of PDE have been recognized, J. A. Beavo et al., TiPS, 11, 150, (1990), and their selective inhibition has led to improved drug therapy, C. D. Nicholson, M. S. Hahid, TiPS, 12, 19, (1991). More particularly, it has been recognized that inhibition of PDE type IV can lead to inhibition of inflammatory mediator release, M. W. Verghese et al., J. Mol. Cell Cardiol., 12 (Suppl. II), S 61, (1989) and airway smooth muscle relaxation (T. J. Torphy in "Directions for New Anti-Asthma Drugs," eds S. R. O'Donnell and C. G. A. Persson, 1988, 37 Birkhauser-Verlag). Thus, compounds that inhibit PDE type IV, but which have poor activity against other PDE types, would inhibit the release of inflammatory mediators and relax airway smooth muscle without causing cardiovascular effects or antiplatelet effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Thromboxane inhibitors, compositions and methods of use Inventor(s): Tejada, Inigo Saenz de; (Madrid, ES) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20030050305 Date filed: November 1, 2002 Abstract: The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxane inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, and, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflanmmatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulants, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction, angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various
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organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles. Excerpt(s): This application is a continuation of PCT/US01/16318 filed May 22, 2001, which claims priority to U.S. Provisional Application No. 60/205,536 filed May 22, 2000. The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxaiie inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, and, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflammatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulaits, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction, angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles. Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorgement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male, vasodilation of the cavernosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387391 (1997). 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 coagulation factor VII-activating protease for the prophylaxis and therapy of vasoproliferative disorders Inventor(s): Kannemeier, Christian; (Giessen, DE), Kanse, Sandip; (Linden-Leihgestern, DE), Preissner, Klaus T.; (Giessen, DE), Roemisch, Juergen; (Voesendorf, AT) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030077271 Date filed: September 26, 2002 Abstract: The use of coagulation factor VII-activating protease (FSAP) for the prophylaxis and/or therapy of vasoproliferative disorders or oncoses is described. Reference is made in particular to the use of the protease for retinopathy, neuropathy, rheumatoid arthritis, psoriasis, endometriosis, bronchitis (especially chronic) or chronic inflammations in the gastrointestinal tract. Excerpt(s): The invention relates to the use of the coagulation factor VII-activating protease for vasoproliferative disorders. The German patent application 199 03 693.4 discloses a protease which is isolated from blood plasma and which is able to activate coagulation factor VII. Also previously described therein are a process for obtaining it, detecting it and inactivating it, and pharmaceutical preparations containing this protease. In accordance with its properties, this protease is referred to as factor seven activating protease (=FSAP). The German patent application 199 03 693.4 additionally reports that FSAP has a plasminogen activator activating and/or potentiating action which can be measured through the activation of single-chain urokinase (scu PA, single chain urokinase plasminogen activator) or single-chain tPA (sctPA, single chain tissue plasminogen activator). The German patent application 199 03 693.4 has also described processes and test systems for the qualitative and quantitative detection of FSAP which are based on measurement of the action reducing the blood clotting times and the actions activating plasminogen activators of FSAP. Test systems of these types also allow FSAP to be measured in complex protein solutions such as plasma, as described in particular in the German patent application 199 26 531.3. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of dextran and other polysaccharides to improve mucus clearance Inventor(s): King, Malcolm; (Edmonton, CA), Speert, David P.; (Vancouver, CA) Correspondence: Gerald F. Swiss; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020032172 Date filed: June 28, 2001 Abstract: This invention relates to the use of polysaccharide such as dextran to improve mucus clearance. In the present invention, dextran has been shown to reduce viscoelasticity and increase mucus clearability of sputum of cystic fibrosis patients. Dextran also reduced viscoelasticity of healthy dog mucus. The present invention therefore may be used to improve mucus clearance in cystic fibrosis patients and treat other conditions associated with defect in airway mucus clearance including chronic bronchitis, bronchiectasis and bronchial asthma.
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Excerpt(s): This invention relates to a method of improving mucus clearance, and more particularly, the invention relates to the use of a polysaccharide such as dextran to improve mucus clearance. Mucus is a critical component of the primary defence mechanism of the respiratory tract, trapping inhaled particulate and microbial material for removal via the mucociliary system. When this mechanism fails to clear sufficiently, mucus accumulates, and must be coughed up as sputum; otherwise it is retained in the respiratory tract, encouraging colonization by microorganisms, which may lead to chronic lung inflammation and obstruction. In cystic fibrosis (CF), airway mucus obstruction has long been considered the most insidious agent of morbidity and mortality. Therapies designed to thin the airway mucus and improve its clearability continue to be a major focus of attention. Airway mucus is a complex, viscoelastic gel whose physical properties are important for airway defence. Mucus is a variable mixture of water, mucous glycoproteins, low molecular weight ions, proteins, and lipids. The three-dimensional structure that forms the mucous gel is dependent upon a number of forms of bonding. The main elements include the following: 1) disulfide bonds--these covalent links are mainly intramolecular, and join glycoprotein subunits into extended macromolecular chains known as mucins. 2) Because of their extended size, these mucin polymers readily form entanglements with neighbouring macromolecules; these act as time-dependent crosslinks, which are susceptible to mechanical degradation. 3) The sugar. units that make up the oligosaccharide sidechains (about 80% of the mucin weight), form hydrogen bonds with complimentary units on neighbouring mucins. Although each bond is weak and readily dissociates, the numbers of bond sites make this type of bonding potentially very important. 4) Mucins are also ionized, containing both positively charged amino acid residues as well as negatively charged sugar units, principally sialic acid and sulfated residues. These increase in airway disease in general, and in CF the proportion of sulfated residues is further elevated because of alterations in glycosyl transferase activities within the Golgi apparatus. The ionic interactions between fixed negative charges result in a stiffer, more extended macromolecular conformation, effectively increasing the polymer size and adding to the numbers of entanglements. 5) Added to this in airway diseases characterized by infection and inflammation, especially CF, are the extra networks of high molecular weight DNA and actin filaments released by dying leukocytes, and exopolysaccharides secreted by bacteria. 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 bronchitis, 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 “bronchitis” (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 bronchitis. You can also use this procedure to view pending patent applications concerning bronchitis. 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 7. BOOKS ON BRONCHITIS Overview This chapter provides bibliographic book references relating to bronchitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bronchitis 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 “bronchitis” (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 bronchitis: •
Living a Healthy Life With Chronic Conditions: Self-Management of Heart Disease, Arthritis, Stroke, Diabetes, Asthma, Bronchitis, Emphysema and Others Source: Palo Alto, CA: Bull Publishing Company. 1994. 296 p. Contact: Available from Bull Publishing Company. P.O. Box 208, Palo Alto, CA 943020208. (800) 676-2855 or (415) 322-2855. Fax (415) 327-3300. E-mail:
[email protected]. PRICE: $14.95. ISBN: 0923521283. Summary: This book is a complete self-management guide for people with chronic diseases. The authors focus on day-to-day living skills, in the context of the specific chronic diseases, including heart disease, arthritis, stroke, diabetes, asthma, bronchitis, and emphysema. General topics include the psychological aspects to self-management; finding resources; smoking and quitting; understanding common symptoms; using one's mind to manage symptoms; exercising for fun and fitness; exercising for flexibility and strength; exercising for endurance; exercising tips for people with specific chronic
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diseases; the importance of communication; durable powers of attorney for health care; eating well; and managing medications. The chapter on diabetes covers diabetes and its causes; maintaining an appropriate blood glucose level; symptoms of hyperglycemia and hypoglycemia; dietary management; exercise; insulin injections; oral medications; emotions; self-monitoring of blood glucose and urine; the complications of diabetes; and diabetes resources. Each chapter includes limited references and a subject index concludes the volume.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “bronchitis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “bronchitis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “bronchitis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Ten-year prospective study of chronic bronchitis in the northeast of England; ISBN: 0443010374; http://www.amazon.com/exec/obidos/ASIN/0443010374/icongroupinterna
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All You Wanted to Know About Chronic Bronchitis by Savitri Ramaiah; ISBN: 8120723023; http://www.amazon.com/exec/obidos/ASIN/8120723023/icongroupinterna
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Asthma & Bronchitis: Symptoms, Causes, Orthodox Treatment - and How Herbal Medicine Will Help (Herbal Health) by Jill Wright; ISBN: 185703760X; http://www.amazon.com/exec/obidos/ASIN/185703760X/icongroupinterna
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Asthma and Bronchitis by Jan de Vries; ISBN: 1851583831; http://www.amazon.com/exec/obidos/ASIN/1851583831/icongroupinterna
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Asthma, Emphysema, and Chronic Bronchitis: Expert Drug Therapy Video Series (Expert Drug Therapy Video Series) by Blanchard, et al (2001); ISBN: 193013813X; http://www.amazon.com/exec/obidos/ASIN/193013813X/icongroupinterna
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Atlas of Bronchitis by Konrad Morgenrath, et al; ISBN: 0407002790; http://www.amazon.com/exec/obidos/ASIN/0407002790/icongroupinterna
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Breathing Free : The Revolutionary 5-Day Program to Heal Asthma, Emphysema, Bronchitis,and Other Respiratory Ailments by Teresa Hale (Author) (2000); ISBN: 0609806343; http://www.amazon.com/exec/obidos/ASIN/0609806343/icongroupinterna
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Bronchitis by R. W. Marz (1998); ISBN: 3805567987; http://www.amazon.com/exec/obidos/ASIN/3805567987/icongroupinterna
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Bronchitis [DOWNLOAD: MICROSOFT READER] by Francois Haas, Sheila Sperber Haas (2000); ISBN: B000056WLD; http://www.amazon.com/exec/obidos/ASIN/B000056WLD/icongroupinterna
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Bronchitis III Proceedings of the third International Symposium on Bronchitis at Groningen, The Netherlands, 23-26 September 1969; ISBN: 9023207041; http://www.amazon.com/exec/obidos/ASIN/9023207041/icongroupinterna
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Bronchitis V: Proceedings of the Fifth International Symposium on Advances of Asthma and COPD, Groningen, Netherlands, 9-11 June, 1993 by Dirkje S. Postma MD (Editor), Jorrit Gerritsen MD (Editor); ISBN: 9023228502; http://www.amazon.com/exec/obidos/ASIN/9023228502/icongroupinterna
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Bronchitis: An International Symposium (1989); ISBN: 902322406X; http://www.amazon.com/exec/obidos/ASIN/902322406X/icongroupinterna
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Bronchitis-Emphys Eczma-Asthma by Oliver H G; ISBN: 0718601394; http://www.amazon.com/exec/obidos/ASIN/0718601394/icongroupinterna
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Chronic Bronchitis and Emphysema: Report by the Industrial Injuries Advisory Council in Accordance with Section 171 of the Social Security Administration Act 1992 Reviewing the Prescription of Chronic Bronchitis and Emphysema for Underground Coal Workers (Cm: 3240) by J.M. Harrington (1996); ISBN: 0101324022; http://www.amazon.com/exec/obidos/ASIN/0101324022/icongroupinterna
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Chronic Bronchitis and Lung Function Abnormalities in Foundry Workers (CRR); ISBN: 0717611906; http://www.amazon.com/exec/obidos/ASIN/0717611906/icongroupinterna
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Chronic Bronchitis in the 90s (Supplement 1: Journal: Respiration)) by D. Olivieri (Editor), Jay A. Nadel (Editor) (1991); ISBN: 3805554524; http://www.amazon.com/exec/obidos/ASIN/3805554524/icongroupinterna
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Chronic Obstructive Pulmonary Disease: Practical, Medical, and Spiritual Guidelines for Daily Living With Emphysema, Chronic Bronchitis, and Combination Diagnosis by Mark Jenkins; ISBN: 1568383509; http://www.amazon.com/exec/obidos/ASIN/1568383509/icongroupinterna
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Coming to terms with chronic bronchitis by John Hargreaves Harley William; ISBN: 0901548235; http://www.amazon.com/exec/obidos/ASIN/0901548235/icongroupinterna
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Contemporary Diagnosis and Management of Bronchitis by Antonio Anzueto; ISBN: 1884065880; http://www.amazon.com/exec/obidos/ASIN/1884065880/icongroupinterna
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Coping With Bronchitis and Emphysema by Tom Smith (1994); ISBN: 0859697096; http://www.amazon.com/exec/obidos/ASIN/0859697096/icongroupinterna
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Cor Pulmonale in Chronic Bronchitis and Emphysema by M. L. Murphy; ISBN: 0879932260; http://www.amazon.com/exec/obidos/ASIN/0879932260/icongroupinterna
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Courage and Information for Life with Chronic Obstructive Pulmonary Disease: The Handbook for Patients, Families and Care Givers Managing COPD, Emphysema, Bronchitis by Rick Carter, et al (2001); ISBN: 1882431073; http://www.amazon.com/exec/obidos/ASIN/1882431073/icongroupinterna
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Diets to help asthma and bronchitis by Roger Newman Turner; ISBN: 0722501625; http://www.amazon.com/exec/obidos/ASIN/0722501625/icongroupinterna
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DK Pocket Healers: Saw Palmetto: Hormone Enhancer - Safe and Effective Self-care for Impotence, Asthma and Bronchitis (DK Pocket Healers Healers) by Stephanie
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Pederson; ISBN: 0751331813; http://www.amazon.com/exec/obidos/ASIN/0751331813/icongroupinterna •
Early detection of chronic bronchitis and pulmonary emphysema by Dan C. Stanescu; ISBN: 0397581890; http://www.amazon.com/exec/obidos/ASIN/0397581890/icongroupinterna
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Emphysema and Chronic Bronchitis. by Stanton. Belinkoff; ISBN: 0316088005; http://www.amazon.com/exec/obidos/ASIN/0316088005/icongroupinterna
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Fact/Book on Sinusitis, Bronchitis and Emphysema and Their Natural Treatment by Clifford Quick; ISBN: 9995344300; http://www.amazon.com/exec/obidos/ASIN/9995344300/icongroupinterna
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For those who live and breathe with emphysema and chronic bronchitis by Thomas L. Petty (Author), Louise M. Nett (Author); ISBN: B00005VY6A; http://www.amazon.com/exec/obidos/ASIN/B00005VY6A/icongroupinterna
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For Those Who Live and Breathe: A Manual for Patients With Emphysema and Chronic Bronchitis by Thomas L. Petty; ISBN: 0398023808; http://www.amazon.com/exec/obidos/ASIN/0398023808/icongroupinterna
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How not to get chronic bronchitis by J. G. Scadding; ISBN: 0900221208; http://www.amazon.com/exec/obidos/ASIN/0900221208/icongroupinterna
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Inflammatory Indices in Chronic Bronchitis (1990); ISBN: 3764323701; http://www.amazon.com/exec/obidos/ASIN/3764323701/icongroupinterna
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Inflammatory Indices in Chronic Bronchitis (Agents and Actions Supplements, Vol 30) by Carl G.A. Persson, et al (1990); ISBN: 0817623701; http://www.amazon.com/exec/obidos/ASIN/0817623701/icongroupinterna
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Leben mit Asthma, Bronchitis, Emphysem. Der richtige Umgang mit Atemwegserkrankungen. by Linus Geisler (Author); ISBN: 3625107856; http://www.amazon.com/exec/obidos/ASIN/3625107856/icongroupinterna
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Living a Healthy Life with Chronic Conditions: Self-Management of Heart Disease, Arthritis, Diabetes, Asthma, Bronchitis, Emphysema & Others by Kate Lorig (Editor), et al; ISBN: 0923521534; http://www.amazon.com/exec/obidos/ASIN/0923521534/icongroupinterna
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Living Well With Chronic Asthma, Bronchitis, and Emphysema by Myra B. Shayevitz, Berton R. Shayevitz (Contributor); ISBN: 0890434166; http://www.amazon.com/exec/obidos/ASIN/0890434166/icongroupinterna
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Living Well With Emphysema and Bronchitis: A Handbook for Everyone With Chronic Obstructive Pulmonary Disease by Myra, Md. Shayevitz, Berton R. Shayevitz; ISBN: 0385194382; http://www.amazon.com/exec/obidos/ASIN/0385194382/icongroupinterna
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Living With Your Bronchitis and Emphysema by Theodore Berland; ISBN: 0312491409; http://www.amazon.com/exec/obidos/ASIN/0312491409/icongroupinterna
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Natural Care Library Saw Palmetto: Safe and Effective Self-Care for Impotence, Asthma, and Bronchitis by Stephanie Pedersen; ISBN: 0789453355; http://www.amazon.com/exec/obidos/ASIN/0789453355/icongroupinterna
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Natural Hist Chronic Bronchitis Emphysema by C. Fletcher, et al (1985); ISBN: 0192611194; http://www.amazon.com/exec/obidos/ASIN/0192611194/icongroupinterna
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Nature cure for bronchitis and emphysema by Clifford Quick; ISBN: 0852690002; http://www.amazon.com/exec/obidos/ASIN/0852690002/icongroupinterna
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Pathology of chronic bronchitis and emphysema by Brian Edyvean Heard; ISBN: 0700014195; http://www.amazon.com/exec/obidos/ASIN/0700014195/icongroupinterna
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Pediatric Bronchitis: Its Tcm Cause, Diagnosis, Treatment & Prevention by Shu-Qin Xiao (Editor), et al; ISBN: 0936185260; http://www.amazon.com/exec/obidos/ASIN/0936185260/icongroupinterna
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Sam Has Bronchitis (Doctory Toby Books) by Andrew Pattison, Virginia Barrett (Illustrator); ISBN: 0947062505; http://www.amazon.com/exec/obidos/ASIN/0947062505/icongroupinterna
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Sinus Survival: A Self-Help Guide for Allergies, Bronchitis, Colds, and Sinusitis by Robert S., Dr. Ivker, Gilbert W. Levitt; ISBN: 0874776848; http://www.amazon.com/exec/obidos/ASIN/0874776848/icongroupinterna
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Sinus Survival: The Holistic Medical Treatment for Allergies, Asthma, Bronchitis, Colds, and Sinusitis by Robert S. Ivker (1995); ISBN: 0874778077; http://www.amazon.com/exec/obidos/ASIN/0874778077/icongroupinterna
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Sinusitis Bronchitis by Clifford Quick; ISBN: 0879831189; http://www.amazon.com/exec/obidos/ASIN/0879831189/icongroupinterna
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Social and emotional effects of chronic bronchitis by M. F. Rubeck; ISBN: 0901548278; http://www.amazon.com/exec/obidos/ASIN/0901548278/icongroupinterna
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Social problems of chronic bronchitis: a study in remedial action by Moira Johnston; ISBN: 0901548197; http://www.amazon.com/exec/obidos/ASIN/0901548197/icongroupinterna
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The chemotherapy of chronic bronchitis and allied disorders by John Robert May; ISBN: 0340049669; http://www.amazon.com/exec/obidos/ASIN/0340049669/icongroupinterna
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The Chronic Bronchitis and Emphysema Handbook by François Haas (Author), Sheila Sperber Haas (Author); ISBN: 047123995X; http://www.amazon.com/exec/obidos/ASIN/047123995X/icongroupinterna
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The Respiratory Solution: How to Use Natural Cures to Reverse Respiratory Ailments: Finally, Relief from Asthma, Bronchitis, Mold, Sinus Attacks, Allergies, Sore Throats, cold by Cassim Igram, Cass, Dr Ingram (2003); ISBN: 1931078025; http://www.amazon.com/exec/obidos/ASIN/1931078025/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “bronchitis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed
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About bronchitis, by A. H. Duncan [pseud.]. Author: Day, Harvey.; Year: 1966; London, Thorsons [c1964]
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Asthmatic bronchitis; a clinical, pathogenetic and therapeutic study, by Mikael Skjelderup Kobro. With bacteriological investigations by Sverre Dick Henriksen. Author: Kobro, Mikael Skjelderup,; Year: 1964; Oslo, Printed by Grøndahl; søn, 1941
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Bronchial asthma and chronic bronchitis in a Swedish urban and rural population; with special reference to prevalence, respiratory function and socio-medical condition, by Lars Irnell and Jaak Kiviloog. [Translated by Maud Marsden]. Author: Irnell, Lars.; Year: 1952; Copenhagen, Munksgaard, 1968
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Bronchitis; second international symposium, 22-24 April 1964, University of Groningen, The Netherlands. Ed. by N. G. M. Orie and H. J. Sluiter. Author: Orie, N. G. M.; Year: 1963; Assen, Royal Vangorcum, 1964
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Bronchitis; the slaughter can be stopped. A survey of "The British disease" and a programme for action. Author: Socialist Medical Association.; Year: 1964; London, Today and Tomorrow Publications [1967?]
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Chronic bronchitis and pulmonary emphysema rehabilitation manual. Author: Chronic Respiratory Diseases Control Program (National Center for Chronic Disease Control); Year: 1941; Arlington, Va. [1967?]
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Chronic bronchitis in Great Britain [by] Leslie H. Capel [and] Maxwell Caplin. Author: Capel, Leslie Henry.; Year: 1964; London, Chest and Heart Assn., 1964
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Chronic Bronchitis, prepared by the Standing Medical Advisory Committee for the Central Health Services Committee and the Minister of Health. Author: Great Britain. Standing Medical Advisory Committee.; Year: 1965; London, 1965
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Chronic bronchitis: its cause and cure. Author: Moyle, Alan.; Year: 1965; London, Thorsons [1969]; ISBN: 722500157
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Coming to terms with chronic bronchitis. Author: Williams, Harley,; Year: 1965; [London] Chest and Heart Association [1970]
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Epidemiology of chronic non-specific lung disease (chronic bronchitis); a critical analysis of three field surveys of CNSLD carried out in the Netherlands. Author: Lende, R. van der.; Year: 1967; Assen, Van Gorcum, 1969
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Field experience with the control of Newcastle disease and infectious bronchitis with inactivated vaccines [by] P. G. Box, S. A. Keeble [and] D. M. Berry. Author: Box, P. G.; Year: 1967; Greenford, Eng. 1966
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For those who live and breathe with emphysema and chronic bronchitis, by Thomas L. Petty and Louise M. Nett. Author: Petty, Thomas L.,; Year: 1965; Springfield, Ill., Thomas [c1967]
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How not to get chronic bronchitis. Author: Scadding, J. G.; Year: 1968; [London] British Medical Assn. [1969]; ISBN: 900221208
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Living with your bronchitis and emphysema [by] Theodore Berland and Gordon L. Snider. Author: Berland, Theodore,; Year: 1967; New York, St. Martin's Press [1972]
in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Nature cure for bronchitis and emphysema. Author: Quick, Clifford.; Year: 1967; Croydon [Eng.] Health for All Pub. Co. [1968]; ISBN: 852690002
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Pathology of chronic bronchitis and emphysema. Author: Heard, Brian Edyvean.; Year: 1967; London, Churchill, 1969; ISBN: 700014195
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Prevalence of respiratory symptoms, chronic bronchitis and pulmonary emphysema in a Finnish rural population; field survey of age group 40-64 in the Harjavalta area. Author: Huhti, Esko.; Year: 1966; Copenhagen, Munksgaard, 1965
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Some aspects of chronic bronchitis; proceedings of a symposium held at the Royal Society of Medicine, London, November 1963. Ed. by F. A. H. Simmonds and L. B. Hunt. Author: Simmonds, Francis Albert Henry.; Year: 1965; Edinburgh, Livingstone, 1964
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Studies of the function of the sweat gland, parotid gland, and the pancreas in chronic bronchitis and heterozygous mucoviscidosis or cystic fibrosis. Author: Toivonen, Seppo.; Year: 1964; Helsinki, 1967
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The bronchitis-emphysema-eczema-asthma complex. Author: Oliver, H. G.; Year: 1965; London, Lewis, 1965
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The chemotherapy of chronic bronchitis and allied disorders. Author: May, J. Robert (John Robert); Year: 1958; London, English Universities Press [1968]; ISBN: 340049669
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The social effects of chronic bronchitis; a Scottish study [by] Mary G. C. Neilson [and] Eileen Crofton. Author: Neilson, Mary G. C.; Year: 1965; Edinburgh, Chest and Heart Assn., 1965
Chapters on Bronchitis In order to find chapters that specifically relate to bronchitis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bronchitis 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 “bronchitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on bronchitis: •
Pulmonary Disease Source: in Little, J.W., et al. Dental Management of the Medically Compromised Patient. 5th ed. St. Louis, MO: Mosby, Inc. 1997. p. 241-259. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $48.00 plus shipping and handling. ISBN: 0815156340. Summary: A working knowledge of the multitude of compromised health states is essential for dental professionals, as the majority of medically compromised patients need or want oral health care. This chapter on pulmonary (lung) disease is from a text that provides the dental practitioner with an up to date reference work describing the dental management of patients with selected medical problems. The authors focus on some of the more commonly encountered pulmonary conditions, including chronic obstructive pulmonary disease (COPD, including chronic bronchitis and emphysema), asthma, and tuberculosis. The authors discuss incidence and prevalence of each
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condition, its etiology (including genetic and lifestyle causes), pathophysiology and complications, signs and symptoms (clinical presentation and laboratory findings), the medical management of patients with pulmonary diseases, and the dental management of this population. 7 figures. 8 tables. 45 references. •
Infection and Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 485-499. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail:
[email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on infection and diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. The authors characterize infections related to diabetes as 'probable' (the data support the presence of the association), 'possible' (presence or absence of an association cannot be established from current data) and 'doubtful' (data argue for no association). People with diabetes probably have a higher risk of the following infections: asymptomatic bacteriuria, lower extremity infections, reactivation tuberculosis in American Indians, infections in surgical wounds after sternotomy and total hip replacement, and group B streptococcal. Support for these associations comes from controlled observational studies in all cases, except for lower extremity infections, where the magnitude of the association between foot and ankle infection and diabetes from hospital-based data appears too great to be explained by detection, selection, or other potential biases. Local and systemic immunologic defects probably account for higher infection rates in patients with diabetes. Autonomic and sensory neuropathy probably account for higher bacteriuria and lower extremity infection rates, while systemic immunologic effects of diabetes may be responsible for the increased risk of surgical wound infection and tuberculosis reinfection. Populationbased data also support a probable higher influenza and pneumonia mortality rate in patients with diabetes. There is a possible association between diabetes and prevalence of the following infections: cystitis, pyelonephritis, candida vulvovaginitis and cystitis, pneumonia, influenza, chronic bronchitis, bacteremia, primary tuberculosis, reactivation tuberculosis in non-American Indians, mucormycosis, malignant otitis externa, and Fournier's gangrene. Doubtful associations exist between diabetes and prevalence of chronic sinusitis or S. aureus colonization (staph infection). 6 tables. 103 references. (AA-M).
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How Vocal Abilities Can Be Limited by Non-Infectious Diseases and Disorders of the Respiratory and Digestive Systems Source: in Thurman, L. and Welch, G., eds. Bodymind and Voice: Foundations of Voice Education, Volumes 1-3. 2nd ed. Collegeville, MN: VoiceCare Network. 2000. p. 546-555. Contact: Available from National Center for Voice and Speech (NCVS). Book Sales, 334 Speech and Hearing Center, University of Iowa, Iowa City, IA 52242. Website: www.ncvs.org. PRICE: $75.00 plus shipping and handling. ISBN: 0874141230. Summary: This chapter on noninfectious diseases and disorders of the respiratory and digestive systems is from a multi-volume text that brings a biopsychosocial approach to the study of the voice. The authors use the phrase 'bodyminds' to describe the
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interrelationship of perception, memory, learning, behavior, and health, as they combine to affect all environmental interactions, adaptations, and learning. The books are written for teachers, voice professionals, people who use their voices on an avocational basis, and interested members of the general public. This chapter describes the effects of smoking and other pollutants, sinusitis and rhinitis, laryngitis, bronchitis and other pulmonary (lung) diseases, the effects of outdoor and indoor air pollution, normal and disordered nasal (nose) conditions, asthma, obstructive sleep apnea, emphysema, and gastroesophageal reflux disease (GERD, the return of stomach acid to the esophagus and larynx). GERD can result in hoarseness, lowering of the average speaking pitch range, increased effort when singing, and a 'tired voice.' Asthma can affect voice primarily by decreasing the ability of the respiratory system to inhale and then pressurize the lung air to create sufficient breathflow between the vocal folds. Asthma symptoms can be triggered by inhalation of allergens or pollutant particles of irritant chemicals, infection, cold air, vigorous exercise, acute neuropsychobiological distress, or even vigorous singing. 68 references. •
Respiratory Disorders Source: in Grundy, M.C.; Shaw, L.; and Hamilton, D.V. Illustrated Guide to Dental Care for the Medically Compromised Patient. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 37-40. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $24.95 plus shipping and handling. ISBN: 0815140223. Summary: This chapter, from an illustrated guide to dental care for medically compromised patients, discusses respiratory disorders. Disorders covered include chronic obstructive pulmonary disease (chronic bronchitis); bronchiectasis; cystic fibrosis; and asthma. For each condition, the authors provide a brief description, the components of medical management, and suggestions for dental care. Illustrations, including photographs, are included. 3 figures.
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CHAPTER 8. MULTIMEDIA ON BRONCHITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on bronchitis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on bronchitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “bronchitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “bronchitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on bronchitis: •
Diagnosing Alpha 1 Antitrypsin Deficiency Source: Minneapolis, MN: Alpha 1 Association. 199x. (videocassette). Contact: Available from Alpha 1 Association. 8120 Penn Avenue, South, Suite 549, Minneapolis, MN 55431-1326. (800) 521-3025 or (612) 703-9979. Fax (612) 703-9977. Email:
[email protected]. Website: www.alpha1.org. PRICE: $3.00 plus shipping and handling. Summary: This videotape program, narrated by Sandra Brandley, the Executive Director of the Alpha 1 National Association, reminds physicians of the symptoms and differential diagnosis of alpha 1 antitrypsin deficiency (A1AD or Alpha 1). The program features Dr. James Stoller, who describes the typical underdiagnosis of A1AD which is typical: the mean time until diagnosis is 7 years (from onset of symptoms) and the mean number of doctors consulted before diagnosis is 3.5. Alpha 1 is a relatively common genetic disorder that affects infants, children, and adults. It is the most common metabolic disorder that causes liver disease in infants and children; the disorder also
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causes cirrhosis and cancer of the liver in adults. Symptoms of A1AD deficiency in children include prolonged obstructive jaundice, low birth weight, mildly elevated liver enzymes, cholestasis, enlarged liver, abnormal bleeding, feeding difficulties, poor growth (or failure to thrive), and ascites (abnormal accumulation of fluids). In adults, the spectrum of liver disease associated with A1AD deficiency varies from mild to severe. Symptoms include chronic active hepatitis, cryptogenic cirrhosis (liver scarring of unknown cause), portal hypertension (high blood pressure in the portal vein of the liver), and hepatocellular carcinoma (liver cancer). A rare but telling symptom is panniculitis, a chronic inflammation of subcutaneous fat featuring ulcerated skin lesions on the torso. Dr. Stoller reminds viewers of the indications for A1AD screening: premature onset of moderate to severe chronic obstructive pulmonary disease (COPD) before age 50; predominant basilar emphysema; chronic bronchitis with airflow obstruction in a nonsmoker; bronchiectasis (irreversible dilation and destruction of the bronchial walls) without clear risk factors; development of unremitting asthma; family history of A1AD; cirrhosis without apparent risk factors; and family history of panniculitis. The program includes a chart of laboratory values and the risk of development of A1AD, and a series of interviews with patients about the interplay of early diagnosis and good quality of life. The program concludes with the contact information for the Alpha 1 National Association (800-521-3025).
Bibliography: Multimedia on Bronchitis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in bronchitis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on bronchitis: •
Asthma, emphysema, and chronic bronchitis [videorecording] Source: [presented by] Blanchard & Loeb Publishers, LLC; Year: 2000; Format: Videorecording; Newark, NJ: Blanchard & Loeb Publishers, c2000
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Asthma, emphysema, and chronic bronchitis [videorecording] Source: produced by Blanchard & Loeb Publishers; Year: 2001; Format: Videorecording; Glenmoore, PA: Blanchard & Loeb Publishers, c2001
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Bronchitis and emphysema [slide] Source: Averill A. Liebow; Year: 1973; Format: Slide; San Diego, Calif.: Liebow: [for sale by Cal-Med Photo, 1973?]
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Chronic bronchitis [videorecording]: assessment and management Source: Faculty of Health Sciences, McMaster University. [et al.]; Year: 1974; Format: Videorecording; Hamilton, Ont.: The University: [for sale by its Faculty of Health Sciences], 1974
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Chronic bronchitis and emphysema [videorecording]: a treatment update Source: University of Washington, Department of Medicine; produced in the facilities of Instructional Media Services, University of Washington; Year: 1991; Format: Videorecording; [Seattle, Wash.]: The University, c1991
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Chronic bronchitis and pulmonary emphysema: the application of physical medicine and rehabilitation, part I [motion picture] Source: Public Health Service, Division of Chronic Diseases and New York University Medical Center, Institute of Physical
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Medicine and; Year: 1965; Format: Motion picture; [Washington]: The Service; [Atlanta: for loan by National Medical Audiovisual Center, 1965] •
Chronic bronchitis and pulmonary emphysema: the application of physical medicine and rehabilitation, part II [motion picture] Source: Public Health Service, Division of Chronic Diseases and New York University Medical Center, Institute of Physical Medicine and; Year: 1964; Format: Motion picture; [Washington]: The Service, [1964]
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Diagnostic tests for bronchitis and emphysema [motion picture] Source: U. S. Department of Health, Education, and Welfare, Public Health Service; Year: 1965; Format: Motion picture; [Washington]: The Service; [Atlanta: for loan by National Medical Audiovisual Center], 1965
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Tracheobronchitis [electronic resource] Source: by Floyd W. Denny, Jr. and Anthony E. Hilger; Year: 1994; Format: Electronic resource; Chapel Hill, NC: Health Sciences Consortium, c1994
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CHAPTER 9. PERIODICALS AND NEWS ON BRONCHITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bronchitis.
News Services and Press Releases One of the simplest ways of tracking press releases on bronchitis 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 “bronchitis” (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 bronchitis. 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 “bronchitis” (or synonyms). The following was recently listed in this archive for bronchitis: •
Inspire scraps bronchitis drug Source: Reuters Industry Breifing Date: November 18, 2002
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Advantages seen with moxifloxacin therapy for bronchitis Source: Reuters Industry Breifing Date: November 04, 2002
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Colonization with C. pneumoniae tied to chronic bronchitis flare-ups Source: Reuters Medical News Date: August 07, 2002
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Popular antibiotic is useless for acute bronchitis Source: Reuters Health eLine Date: May 10, 2002
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Azithromycin ineffective in treating acute bronchitis Source: Reuters Industry Breifing Date: May 09, 2002
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Patient education reduces antibiotic use for bronchitis Source: Reuters Industry Breifing Date: January 11, 2002
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Bristol-Myers' Tequin gets additional approval for acute chronic bronchitis Source: Reuters Industry Breifing Date: November 07, 2001
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Occupation may raise risk of chronic bronchitis Source: Reuters Health eLine Date: July 09, 2001
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Sleep apnea twice as common in bronchitis patients as in healthy subjects Source: Reuters Medical News Date: July 03, 2001
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Inspire suspends bronchitis drug trial enrollment Source: Reuters Industry Breifing Date: April 24, 2001 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
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Market Wire’s home page at http://www.marketwire.com/mw/home, type “bronchitis” (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 “bronchitis” (or synonyms). If you know the name of a company that is relevant to bronchitis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “bronchitis” (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 “bronchitis” (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 bronchitis: •
Smoking and Lupus: A Double Whammy! Source: Lupus News. 20(3): 3,9. Summer 2000. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article provides people who have lupus with information on the impact of smoking on lupus. The article presents evidence demonstrating that smoking complicates and accelerates the adverse effects of lupus. For example, smoking cigarettes increases the risk of pneumonococcal pneumonia and chronic bronchitis, and people who have lupus are more susceptible to infections, particularly respiratory infections. People who have lupus and who smoke have a greater risk of coronary artery disease. Both lupus and smoking can affect blood vessels and circulation, kidney and liver function, wound healing, the digestive system, hair, and bone density. In addition, lupus can cause skin disease, which may be effectively treated with antimalarial
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medications, but smoking interferes with the benefits of these medications. The article also offers tips for smoking cessation.
Academic Periodicals covering Bronchitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bronchitis. In addition to these sources, you can search for articles covering bronchitis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. 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 bronchitis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with bronchitis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to bronchitis: Azithromycin •
Systemic - U.S. Brands: Zithromax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202642.html
Bronchodilators, Adrenergic •
Inhalation - U.S. Brands: Adrenalin Chloride; Airet; Alupent; Arm-a-Med Isoetharine; Arm-a-Med Metaproterenol; Asthmahaler Mist; AsthmaNefrin; Beta2; Brethaire; Bronkaid Mist; Bronkaid Suspension Mist; Bronkometer; Bronkosol; Dey-Lute Isoetharine; Dey-Lute Metaproterenol; Isupr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202095.html
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Oral/Injection - U.S. Brands: Adrenalin; Alupent; Ana-Guard; Brethine; Bricanyl; EpiPen Auto-Injector; EpiPen Jr. Auto-Injector; Isuprel; Proventil; Proventil Repetabs; Ventolin; Volmax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202096.html
Bronchodilators, Theophylline •
Systemic - U.S. Brands: Aerolate Sr; Asmalix; Choledyl; Choledyl SA; Elixophyllin; Lanophyllin; Phyllocontin; Quibron-T Dividose; Quibron-T/SR Dividose; Respbid; Slo-Bid Gyrocaps; Slo-Phyllin; Theo-24; Theobid Duracaps; Theochron; Theo-Dur; Theolair; Theolair-SR; Theo-Time; Th http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/201945.html
Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed •
Systemic - U.S. Brands: Acel-Imune; Certiva; Infanrix; Tripedia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202201.html
Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed and Haemophilus B Conjugate Vaccine •
Systemic - U.S. Brands: Tetramune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202911.html
Dyphylline •
Systemic - U.S. Brands: Dilor; Dilor-400; Lufyllin; Lufyllin-400 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202752.html
Ipratropium •
Inhalation - U.S. Brands: Atrovent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202304.html
Ipratropium and Albuterol •
Inhalation-Local - U.S. Brands: Combivent; DuoNeb http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203487.html
Loracarbef •
Systemic - U.S. Brands: Lorabid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202680.html
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Oxtriphylline and Guaifenesin •
Systemic - U.S. Brands: Brondelate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202430.html
Palivizumab •
Systemic - U.S. Brands: Synagis http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203646.html
Penicillins and Beta-Lactamase Inhibitors •
Systemic - U.S. Brands: Augmentin; Timentin; Unasyn; Zosyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202705.html
Respiratory Syncytial Virus Immune Globulin Intravenous •
Systemic - U.S. Brands: RespiGam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203069.html
Sparfloxacin •
Systemic - U.S. Brands: Zagam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203530.html
Sulfonamides and Trimethoprim •
Systemic - U.S. Brands: Bactrim; Bactrim DS; Bactrim I.V.; Bactrim Pediatric; Cofatrim Forte; Cotrim; Cotrim DS; Cotrim Pediatric; Septra; Septra DS; Septra Grape Suspension; Septra I.V.; Septra Suspension; Sulfatrim; Sulfatrim Pediatric; Sulfatrim S/S; Sulfatrim Suspension; S http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202781.html
Theophylline and Guaifenesin •
Systemic - U.S. Brands: Bronchial; Elixophyllin-GG; Glyceryl-T; Quibron; Quibron-300; Theocon; Theolate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202557.html
Theophylline, Ephedrine, and Hydroxyzine •
Systemic - U.S. Brands: Marax; Marax-DF http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202555.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing
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information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
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/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
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/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 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:14 •
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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
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
13
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). 14 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “bronchitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “bronchitis” (or synonyms) into the “For these words:” box. The following is a sample result: •
Garlic Contact: AIDS Project Los Angeles, 3550 Wilshire Blvd Ste 300, Los Angeles, CA, 900102404, (213) 201-1600, http://www.apla.org. Summary: This is a compilation of material on the use of garlic as a preventive medicine. From ancient Egypt up to modern-day U.S., garlic has been used treat a myriad of medical problems, including indigestion and bronchitis. Today, its potential in cancer prevention and AIDS treatment is being studied. A New York Times reprint highlights preliminary studies that suggest that garlic does have a significant medicinal value. Results of a pilot study treating AIDS patients with garlic as supportive care are included in the packet. In August of 1990,the First World Congress on the Health Significance of Garlic and Garlic Components examined the efficacy of an intravenous extract of garlic in the treatment of cryptococcal meningitis and cytomegalovirus infection in AIDS. The packet contains a wide variety of other published papers on the medical uses for garlic, bibliographies, and a book chapter.
•
Health and the American child: Part 1: A focus on mortality among children: Risks, trends, and priorities for the twenty-first century Source: [Washington, DC]: Public Health Policy Advisory Board. 1999. ca. 200 pp. Contact: Available from Public Health Policy Advisory Board, 1350 Eye Street, Suite 200, Washington, DC 20005. Telephone: (202) 312-8238 / fax: (202) 842-2676 / e-mail:
[email protected] / Web site: http://www.phpab.org. Available from the Web site at no charge. Summary: This report provides a summary of the patterns and trends of the major contributors to death in children, highlighting important risk factors, relevant interventions, available resources, and recommendations for further reducing child mortality. The report is intended for policy makers, opinion leaders, and the public. It includes chapters on the following: (1) a profile of America's children; (2) mortality patterns in 1995; (3) trends in overall mortality; (4) trends in specific causes of death; (5) actual causes of death; (6) special topics such as suicide, violence, asthma, bronchitis,
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and cancer; (7) economic and social factors; (8) cost-effectiveness of interventions to lower risk; and (9) resources for children's health.
The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “bronchitis” (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 26249 399 138 119 8 26913
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “bronchitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
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 Biologists20 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.21 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.22 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/.
20 Adapted 21
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. 22 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 bronchitis 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 bronchitis. 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 bronchitis. 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 “bronchitis”:
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•
Other guides Asthma http://www.nlm.nih.gov/medlineplus/asthma.html Breathing Problems http://www.nlm.nih.gov/medlineplus/breathingproblems.html Bronchitis http://www.nlm.nih.gov/medlineplus/bronchitis.html Cartilage Disorders http://www.nlm.nih.gov/medlineplus/cartilagedisorders.html COPD http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.t ml Emphysema http://www.nlm.nih.gov/medlineplus/emphysema.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html
Within the health topic page dedicated to bronchitis, the following was listed: •
General/Overviews Acute Bronchitis Source: American Academy of Family Physicians http://familydoctor.org/handouts/677.html Bronchitis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00031
•
Diagnosis/Symptoms Blood Gas Tests Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/blood_gases/test.html Spirometry Source: National Lung Health Education Program http://www.nlhep.org/spirom1.html Understanding PFT's (Pulmonary Function Testing) Source: Alpha 1 Association http://www.alpha1.org/what/lunginfo_pfts.htm
•
Treatment AHRQ Report Says Doctors Commonly Treat Bronchiolitis with Medicines that May Be Ineffective Source: Agency for Healthcare Research and Quality http://www.ahrq.gov/news/press/pr2003/bronchpr.htm
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Children Bronchiolitis Source: Nemours Foundation http://kidshealth.org/parent/infections/lung/bronchiolitis.html
•
From the National Institutes of Health Lungs in Health and Disease Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/lungs_hd.pdf
•
Latest New Deaths from Chronic Lung Disease Underestimated Source: 10/28/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14458 .html Red Wine Could Be Good for Your Lungs Source: 10/28/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14457 .html
•
Organizations American Lung Association http://www.lungusa.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ National Lung Health Education Program http://www.nlhep.org/
•
Pictures/Diagram Atlas of the Body: The Respiratory System -- Structure Detail Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ8PPLCGJC &sub_cat=285
•
Statistics FASTATS: Bronchitis Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/brnchtis.htm
•
Teenager Bronchitis Source: Nemours Foundation http://kidshealth.org/teen/infections/common/bronchitis.html
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You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on bronchitis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Cigars: More Dangerous Than You Think Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1999. 15 p. Contact: Available from Channing L. Bete Co., Inc. 200 State Road, South Deerfield, MA 01373. (800) 628-7733. Fax (800) 499-6464. E-mail:
[email protected]. Website: www.channing-bete.com. PRICE: $1.05 for 1-99 copies; bulk copies available. Item number 73958B-01-99. Summary: This booklet describes the health hazards associated with smoking cigars. Contrary to a popular myth that cigar smoking is a harmless habit, the booklet explains that cigars can be addictive because of their nicotine content. The booklet explores why people start smoking cigars; the publicity and imaging that surrounds cigars and cigar users; how smoking causes cancer of the mouth, larynx, esophagus, and lungs; other risks associated with smoking cigars, including emphysema and chronic bronchitis, heart disease, and nicotine addiction; the problem of secondhand cigar smoke; and the impact of cigar smoking on one's breath, teeth, hair, clothes, and home. The booklet includes a section of ideas on how to handle a variety of situations where smoking may be encountered; and another section on tips for quitting cigar smoking. One sidebar lists the telephone numbers for some organizations through which readers can get more information. The brochure is illustrated with line drawings of a variety of people, depicted in everyday settings.
•
Your Child and Antibiotics: Unnecessary Antibiotics CAN Be Harmful Source: Elk Grove Village, IL: American Academy of Pediatrics (AAP). 1997. [2 p.].AV.Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. PRICE: $24.95 per 100 copies (100 copies minimum); $29.95 per 100 copies (non-members). Contact: Available from American Academy of Pediatrics. Division of Publications, 141 Northwest Point Boulevard, P.O. Box 927, Elk Grove Village, IL 60009-0927. (800) 4339016 or (847) 228-5005; Fax (847) 228-1281; http://www.aap.org. PRICE: $24.95 per 100 copies (100 copies minimum); $29.95 per 100 copies (non-members).
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Summary: This brochure from the American Academy of Pediatrics informs parents about the over-use of antibiotics, the potential for antibiotic-resistant bacteria strains to develop, and how to determine when antibiotics are needed and when they are not. The brochure stresses that repeated and improper use of antibiotics are some of the main causes of the increase in resistant bacteria. Some of these resistant bacteria can be treated with more powerful medicines, which may need to be given intravenously in the hospital, and a few resistant bacteria are already untreatable. The brochure lists common diagnoses and the likelihood that antibiotics are indicated. These include ear infections, sinus infections, cough or bronchitis, sore throat, and colds. Although viral infections may sometimes lead to bacterial infections, treating viral infections with antibiotics to prevent bacterial infections does not work, and may lead to infection with resistant bacteria. The brochure concludes with the answers to a brief list of commonly asked questions. The brochure is illustrated with full-color photographs of children. •
Respiratory Problems Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org. Summary: This fact sheet, written for persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses various opportunistic respiratory infections and diseases. Respiratory problems are common in individuals with HIV/AIDS. Disorders of the lower tract include bronchitis, pneumonia, and lung tumors. Other disorders include bacterial pneumonia, tuberculosis, pneumocystis pneumonia, mycobacterium avium complex (MAC), cytomegalovirus (CMV), Kaposi's sarcoma, and lymphoma. The symptoms of bronchitis include chest cough that produces phlegm, chest discomfort, severe chest pain, and shortness of breath. The symptoms of pneumonia are a sudden onset of fever, pleuritic chest pain, shortness of breath, cough with pus-like phlegm, fatigue, a dry non-productive cough, and weight loss. Respiratory problems are often diagnosed through a physical examination, a chest x-ray, expectorated or induced sputum, oximetry or arterial blood gases, bronchoscopy with biopsy, and a lung biopsy. The fact sheet identifies the treatments available to HIVpositive individuals for bronchitis and bacterial pneumonia. The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “bronchitis” (or synonyms). The following was recently posted: •
Principles of appropriate antibiotic use for treatment of acute bronchitis in adults Source: American College of Physicians - Medical Specialty Society; 2001 March 20; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2745&nbr=1971&a mp;string=bronchitis
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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Chronic Bronchitis Summary: This consumer fact sheet describes bronchitis and discusses its causes, prognosis, and treatment options. Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2167 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 bronchitis. 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/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to bronchitis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bronchitis.
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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 bronchitis. 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 “bronchitis” (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 “bronchitis”. 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 “bronchitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “bronchitis” (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.23
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
23
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)24: •
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/
24
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on bronchitis: •
Basic Guidelines for Bronchitis Bronchitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001087.htm Chronic bronchitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000119.htm
•
Signs & Symptoms for Bronchitis Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Leg swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm
214 Bronchitis
Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Vision abnormalities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Wheezing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003070.htm •
Diagnostics and Tests for Bronchitis Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm Pulmonary function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003853.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm
•
Background Topics for Bronchitis Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Cigarette smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
215
BRONCHITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine
216 Bronchitis
derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [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]
Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making
Dictionary 217
emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Air Pollutants: Substances which pollute the air. [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] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha 1-Antichymotrypsin: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity
218 Bronchitis
in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amaurosis: Partial or total blindness from any cause. [NIH] Amaurosis Fugax: Partial amaurosis, which is sudden and transitory, and associated with headache, vertigo, and nausea. [NIH] Ambroxol: A metabolite of bromhexine that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]
Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of
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organic materials during a large number of metabolically important reactions. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] 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] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH]
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Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] 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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [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] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [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] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or
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reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] 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] 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] Antiplasmin: A member of the serpin superfamily found in human plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. It is a glycoprotein, molecular weight approximately 70,000 that migrates in the alpha 2 region in immunoelectrophoresis. It is the principal plasmin inactivator in blood, rapidly forming a very stable complex with plasmin. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH]
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Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apnoea: Cessation of breathing. [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] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied
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in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atelectasis: Incomplete expansion of the lung. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH]
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Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] 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]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [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
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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 Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either non-
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synthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biotype: A group of individuals having the same genotype. [NIH] Bisoprolol: A cardioselective beta-1-adrenergic blocker. It is effective in the management of hypertension and angina pectoris. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [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 Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH]
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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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] 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] Bronchial Hyperreactivity: Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory. [NIH] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiolitis Obliterans: Inflammation of the bronchioles with obstruction by fibrous granulation tissue or bronchial exudate. It may follow inhalation of irritating gases or foreign bodies and it complicates pneumonia. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] 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] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [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] Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH]
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Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [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]
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Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catarrh: Inflammation of a mucous membrane, with a free discharge (Hippocrates); especially such inflammation of the air passages of the head and throat. [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] 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] Cefaclor: Semisynthetic, broad-spectrum antibiotic derivative of cephalexin. [NIH] Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [NIH]
Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges,
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eyes, inner ears, and urinary tract. [NIH] Cefuroxime: Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, gonorrhea, and haemophilus. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell 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] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cephaloridine: A cephalosporin antibiotic. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar,
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subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] 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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of
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chlorinated lime, which is used in fabric bleaching. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] 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] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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 Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [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] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of
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certain fractures. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Claudication: Limping or lameness. [EU] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clitoral: Pertaining to the clitoris. [EU] 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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of
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the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement 1: The first complement component to act in the cytolysis reaction. It is a trimolecular complex held together with Ca ions and, when activated, has esterase activity which initiates the next step in the sequence. [NIH] Complement 1 Inactivators: Compounds which inhibit, antagonize, or inactivate complement 1. A well-known inhibitor is a serum glycoprotein believed to be alpha-2neuroaminoglycoprotein. It inhibits the activated (esterase) form of complement 1 as well as kinin-forming, coagulation, and fibrinolytic systems. Deficiency of this inactivator has been found in patients with hereditary angioneurotic edema. These compounds are members of the serpin superfamily. [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,
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spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral
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or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronavirus: A genus of the family Coronaviridae which causes respiratory or gastrointestinal disease in a variety of vertebrates. [NIH] Corpus: The body of the uterus. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be
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classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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 anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU]
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Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [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] Decongestant: An agent that reduces congestion or swelling. [EU] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH]
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Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [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] Desquamation: The shedding of epithelial elements, chiefly of the skin, in scales or small sheets; exfoliation. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH]
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Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulphide: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH] Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dose-rate: The strength of a treatment given over a period of time. [NIH] Drip: The continuous slow introduction of a fluid containing nutrients or drugs. [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] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or
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incomplete movements. [EU] Dysmenorrhea: Painful menstruation. [NIH] Dysmenorrhoea: Painful menstruation. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emollient: Softening or soothing; called also malactic. [EU]
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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] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH]
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Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Environmental Microbiology: The study of microorganisms living in a variety of environments (air, soil, water, etc.) and their pathogenic relationship to other organisms including man. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemics: A period of increased prevalence of a particular disease in a population. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] 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
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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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH]
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Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Exfoliation: A falling off in scales or layers. [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] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]
Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [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] Facial: Of or pertaining to the face. [EU]
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Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [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] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fenoterol: An adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filarioidea: A superfamily of nematodes of the suborder Spirurina. Its organisms possess a filiform body and a mouth surrounded by papillae. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so
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that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fleroxacin: A third-generation fluoroquinolone derivative with a broad antimicrobial spectrum. The drug strongly inhibits the DNA-supercoiling activity of DNA gyrase which may account for its antibacterial activity. [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] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Formulary: A book containing a list of pharmaceutical products with their formulas and means of preparation. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] 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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallic Acid: A colorless or slightly yellow crystalline compound obtained from nutgalls. It is used in photography, pharmaceuticals, and as an analytical reagent. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [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] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines,
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characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [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] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU]
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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 participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH]
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Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] 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] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [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]
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Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]
Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Haematemesis: The vomiting of blood. [EU] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Haemophilus influenzae: A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. [NIH]
Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Healthy Worker Effect: Phenomenon of workers' usually exhibiting overall death rates lower than those of the general population due to the fact that the severely ill and disabled are ordinarily excluded from employment. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and
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mature. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]
Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous
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chromosomes. [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] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydration: Combining with water. [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] Hydroxybenzoic Acids: Benzoic acid substituted by one or more hydroxy groups in any position on the benzene ring. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH]
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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] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Pulmonary: Increased pressure within the pulmonary circulation, usually secondary to cardiac or pulmonary disease. [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] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoventilation: A reduction in the amount of air entering the pulmonary alveoli. [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] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] 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-response: The production of antibodies or particular types of cytotoxic lymphoid cells on challenge with an antigen. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer
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factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] 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] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH]
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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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [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]
Infectious Bursal Disease Virus: A species of Avibirnavirus causing severe inflammation of the bursa of Fabricius in chickens and other fowl. Transmission is thought to be through contaminated feed or water. Vaccines have been used with varying degrees of success. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
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] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhalation Exposure: The exposure to potentially harmful chemical, physical, or biological agents by inhaling them. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH]
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Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] 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] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-5: Factor promoting eosinophil differentiation and activation in hematopoiesis. It also triggers activated B-cells for a terminal differentiation into Ig-secreting cells. [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
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stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]
Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis, marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [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]
Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipratropium: A muscarinic antagonist structurally related to atropine but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic. [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.
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Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Ivermectin: A mixture of ivermectin component B1a (RN 71827-03-7) and B1b (RN 70209-813), which is a semisynthetic product from Streptomyces avermitilis. A potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasite infestations in animals. The compound has activity against internal and external parasites and has been found effective against arthropods, insects, nematodes, filarioidea, platyhelminths, and protozoa. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [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] Keratosis: Any horny growth such as a wart or callus. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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 stone: A stone that develops from crystals that form in urine and build up on the
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inner surfaces of the kidney, in the renal pelvis, or in the ureters. [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] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] 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] Laryngitis: Inflammation of the larynx. This condition presents itself with dryness and soreness of the throat, difficulty in swallowing, cough, and hoarseness. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukemic Infiltration: A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site. [NIH] Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukostasis: Abnormal intravascular leukocyte aggregation and clumping often seen in
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leukemia patients. The brain and lungs are the two most commonly affected organs. This acute syndrome requires aggressive cytoreductive modalities including chemotherapy and/or leukophoresis. It is differentiated from leukemic infiltration which is a neoplastic process where leukemic cells invade organs. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] 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] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different
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degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] 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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphadenitis: Inflammation of the lymph nodes. [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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH]
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Lyssavirus: A genus of the family Rhabdoviridae that includes rabies virus and other rabieslike viruses. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mass Media: Instruments or technological means of communication that reach large numbers of people with a common message: press, radio, television, etc. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Mechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptors include hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with nonneural accessory structures. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU]
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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 Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU]
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Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineral Oil: A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient. [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
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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] 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] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]
Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] 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] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH]
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Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [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] Mucociliary Clearance: Rate of ciliary and secretory activity of the respiratory submucosal glands. It is a non-specific host defense mechanism, measurable in vivo by mucus transfer, ciliary beat frequency, and clearance of radioactive tracers. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycobacteriosis: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH]
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Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]
Mycobacterium avium: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans. [NIH] Mycobacterium avium Complex: A complex that includes several strains of M. avium. M. intracellulare is not easily distinguished from M. avium and therefore is included in the complex. These organisms are most frequently found in pulmonary secretions from persons with a tuberculous-like mycobacteriosis. Strains of this complex have also been associated with childhood lymphadenitis and AIDS. M. avium alone causes tuberculosis in a variety of birds and other animals, including pigs. [NIH] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] N-acetyl: Analgesic agent. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH]
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Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Negative Staining: The technique of washing tissue specimens with a concentrated solution of a heavy metal salt and letting it dry. The specimen will be covered with a very thin layer of the metal salt, being excluded in areas where an adsorbed macromolecule is present. The macromolecules allow electrons from the beam of an electron microscope to pass much more readily than the heavy metal; thus, a reversed or negative image of the molecule is created. [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] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [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] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH]
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Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [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]
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Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] 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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic
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under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [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] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] 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] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [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] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying
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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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paramyxovirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have both hemagglutinin and neuraminidase activities and encode a C protein. Human parainfluenza virus 1 is the type species. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patent ductus arteriosus: Abnormal persistence of the opening in the arterial duct that connects the pulmonary artery to the descending aorta; this opening normally closes within 24 hours of birth. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease.
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[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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Peak flow: The maximum amount of air breathed out; the power needed to produce this amount. [EU] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] 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] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Periodontal Attachment Loss: Loss or destruction of periodontal tissue caused by periodontitis or other destructive periodontal diseases or by injury during instrumentation. Attachment refers to the periodontal ligament which attaches to the alveolar bone. It has been hypothesized that treatment of the underlying periodontal disease and the seeding of periodontal ligament cells enable the creating of new attachment. [NIH]
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Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal Ligament: Fibrous connective tissue surrounding the root of a tooth that separates it from and attaches it to the alveolar bone. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral 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] Periplasm: The space between the inner and outer membranes of a cell that is shared with the cell wall. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [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]
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Pharyngitis: Inflammation of the throat. [NIH] 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] Phenylephrine: An alpha-adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs
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of disease or abnormality. [NIH] Physical Medicine: A medical specialty concerned with the use of physical agents, mechanical apparatus, and manipulation in rehabilitating physically diseased or injured patients. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pivampicillin: Pivalate ester analog of ampicillin. [NIH] Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight
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of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasminogen Inactivators: Important modulators of the activity of plasminogen activators. Four inhibitors, all belonging to the serpin family of proteins, have been implicated in plasminogen activation inhibition. They are PAI-1, PAI-2, protease-nexin, and protein C inhibitor (PAI-3). All inhibit both the tissue-type and urokinase-type plasminogen activators. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] 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] Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pneumonectomy: An operation to remove an entire lung. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short
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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] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH]
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Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial
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infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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,
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Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. [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 Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [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] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of
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pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [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] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Rabies Virus: The type species of lyssavirus causing rabies in humans and other animals. Transmission is mostly by animal bites through saliva. The virus is neurotropic multiplying in neurons and myotubes of vertebrates. [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] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH]
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Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] 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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]
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Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] 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] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respirable: Dust particles smaller than 0. 005 mm, which are deposited in the respiratory region of the lungs. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory 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]
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Respiratory Mechanics: The physical or mechanical action of the lungs, diaphragm, ribs, and chest wall during respiration. It includes airflow, lung volume, neural and reflex controls, mechanoreceptors, breathing patterns, etc. [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] 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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested
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as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [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] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [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] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH]
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Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit serine endopeptidases. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of serine endopeptidases, and some serpins occur in plants
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where their function is not known. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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]
Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] 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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH]
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Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft Tissue Injuries: Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as "soft tissue injuries of the hand". [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural
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orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, 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] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Stabilization: The creation of a stable state. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and
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occur in the natural environment. [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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] 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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] 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] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfur Dioxide: A highly toxic, colorless, nonflammable gas. It is used as a pharmaceutical aid and antioxidant. It is also an environmental air pollutant. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] 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]
Surgical Wound Infection: Infection occurring at the site of a surgical incision. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH]
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Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] 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] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachykinins: A family of biologically active peptides sharing a common conserved Cterminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Tandem Repeat Sequences: Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (inverted tandem repeats). [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the
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skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [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] Thermoregulation: Heat regulation. [EU] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may
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take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Toothache: Pain in the adjacent areas of the teeth. [NIH] Topical: On the surface of the body. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in
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extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] 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] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] 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] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [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] 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
Dictionary 297
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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] 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] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] 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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]
Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH]
298 Bronchitis
Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH]
Dictionary 299
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Vulvovaginitis: Inflammation of the vulva and vagina, or of the vulvovaginal glands. [EU] War: Hostile conflict between organized groups of people. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH]
300 Bronchitis
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]
Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to 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] Zinc Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [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]
301
INDEX A Abdominal, 215, 239, 248, 259, 273, 275, 297 Abdominal Pain, 215, 248, 259, 297 Aberrant, 19, 142, 215 Acceptor, 215, 261, 272, 294, 296 Acetylcholine, 43, 215, 232, 270 Acetylcholinesterase, 43, 215 Acetylcysteine, 215 Acne, 25, 138, 157, 215, 259 Acne Vulgaris, 215, 259 Actin, 167, 215 Acyl, 159, 215 Acylation, 146, 215 Adaptability, 215, 230 Adaptation, 149, 215 Adenine, 215, 283 Adenocarcinoma, 215, 252 Adenosine, 163, 215, 276 Adipose Tissue, 216, 273 Adjustment, 125, 215, 216 Adjuvant, 148, 216, 248 Adoptive Transfer, 56, 216 Adrenal Cortex, 216, 236, 285 Adrenal Medulla, 143, 216, 243, 271 Adrenergic, 52, 130, 148, 188, 216, 223, 226, 243, 246, 276, 280 Adsorption, 48, 216 Adsorptive, 216 Adverse Effect, 8, 185, 216, 240, 259, 289 Aerobic, 216, 268, 282 Aerosol, 8, 9, 22, 98, 99, 132, 137, 138, 149, 157, 216 Aetiology, 82, 216 Afferent, 11, 216, 246, 276 Affinity, 11, 156, 216, 217, 223, 290 Agar, 141, 216, 237, 255, 277 Agonist, 10, 52, 143, 217, 246, 270, 276 Agoraphobia, 217, 276 Air Pollutants, 23, 217 Air Sacs, 151, 217, 218 Airway Obstruction, 8, 9, 108, 217 Airway Resistance, 143, 217 Alanine, 35, 41, 153, 217 Albumin, 217, 272, 277 Aldehydes, 43, 217 Algorithms, 217, 225 Alkaline, 217, 218, 228
Alkaloid, 217, 223, 270, 277 Allergen, 17, 51, 217, 239, 288 Allergic Rhinitis, 47, 136, 139, 140, 144, 160, 163, 165, 217, 228 Allo, 46, 217 Allogeneic, 19, 67, 217, 250 Allogeneic bone marrow transplantation, 67, 217 Allograft, 8, 19, 56, 165, 217 Alpha 1-Antichymotrypsin, 217, 288 Alpha 1-Antitrypsin, 13, 218, 288 Alpha 1-Antitrypsin Deficiency, 13, 218 Alpha Particles, 218, 283 Alternative medicine, 184, 218 Aluminum, 7, 218 Alveolar Process, 218, 285 Alveoli, 38, 151, 153, 218, 282, 298 Amaurosis, 162, 218 Amaurosis Fugax, 162, 218 Ambroxol, 74, 218 Ambulatory Care, 65, 218 Amine, 218, 253 Amino Acid Sequence, 41, 218, 221, 248, 288 Ammonia, 22, 218, 292, 297 Amoxicillin, 63, 71, 91, 219 Ampicillin, 219, 277 Amplification, 46, 219 Ampulla, 219, 232 Amyloid, 219, 231 Anaemia, 131, 132, 147, 219 Anaerobic, 219, 251 Anaesthesia, 219, 256 Anal, 27, 219, 243, 246, 261 Analgesic, 28, 219, 268 Analog, 137, 219, 277 Analogous, 144, 219, 278, 296 Analytes, 200, 219 Anaphylactic, 98, 219 Anaphylatoxins, 219, 234 Anaphylaxis, 219 Anaplasia, 219 Anatomical, 219, 239, 255, 287 Androgens, 216, 219, 236 Anemia, 220, 226, 228, 233 Anesthesia, 217, 220, 223, 242 Aneurysm, 220, 222, 298
302 Bronchitis
Angina, 80, 139, 161, 162, 163, 164, 220, 226, 281 Angina Pectoris, 80, 163, 164, 220, 226, 281 Angiogenesis, 12, 220, 263 Angiopathy, 220, 231 Angioplasty, 139, 140, 163, 164, 220, 223, 268 Angiotensinogen, 220, 285, 288 Animal model, 8, 11, 21, 23, 24, 27, 34, 39, 45, 47, 65, 220 Anions, 217, 220, 258, 280 Ankle, 176, 220 Annealing, 220, 279 Anorexia, 220, 248 Antagonism, 93, 160, 220 Antiallergic, 130, 220, 236 Antiarrhythmic, 220, 258 Antibacterial, 64, 143, 220, 229, 233, 247, 280, 290 Antibodies, 23, 33, 41, 43, 46, 221, 244, 251, 254, 255, 262, 266, 277 Antibody, 54, 153, 216, 221, 234, 251, 253, 255, 256, 258, 264, 266, 283, 288, 290, 300 Anticoagulant, 221, 281 Antigen-Antibody Complex, 221, 234 Antigen-presenting cell, 28, 221 Anti-infective, 221, 253 Anti-inflammatory, 28, 130, 137, 146, 149, 221, 222, 236, 239, 249 Anti-Inflammatory Agents, 137, 221, 222, 236 Antimicrobial, 25, 64, 68, 83, 84, 88, 92, 109, 221, 230, 232, 247 Antineoplastic, 221, 236, 247 Antioxidant, 53, 80, 100, 221, 272, 292 Antiplasmin, 221, 288 Antiseptic, 221, 229, 300 Antitussive, 144, 147, 221 Antiviral, 215, 221, 247, 274 Anus, 219, 221, 226, 258, 278 Aorta, 221, 222, 236, 240, 273 Aortic Aneurysm, 21, 222 Apnea, 222 Apnoea, 82, 91, 222 Apoptosis, 20, 43, 51, 56, 59, 61, 100, 222, 229 Appendicitis, 4, 222 Aqueous, 222, 224, 229, 237, 242, 253 Arachidonate 12-Lipoxygenase, 222, 261 Arachidonate 15-Lipoxygenase, 222, 261 Arachidonate Lipoxygenases, 222, 261 Arginine, 219, 222, 270, 296, 297
Aromatic, 222, 232, 276, 293 Arrestin, 50, 222 Arterial, 203, 222, 228, 231, 232, 254, 258, 273, 281, 293, 296 Arteries, 140, 164, 220, 221, 222, 226, 236, 258, 265, 268, 282 Arteriolar, 222, 227, 285 Arterioles, 222, 226, 228, 265, 268 Arteriovenous, 222, 231, 265 Articular, 222, 272 Ascites, 180, 222 Aspergillus, 67, 81, 87, 222 Aspiration, 77, 85, 222 Aspirin, 28, 222 Assay, 46, 223 Astringent, 223, 229, 300 Astrocytes, 50, 223 Asymptomatic, 81, 176, 223 Atelectasis, 67, 223 Atenolol, 80, 223 Atherectomy, 223, 242 Atopic, 102, 135, 136, 144, 223 Atrophy, 223, 244 Atropine, 223, 258 Attenuated, 132, 142, 223 Autoimmune disease, 136, 223, 267 Autologous, 46, 223 Autonomic, 176, 215, 223, 271, 275 Autonomic Nervous System, 223, 275 Autopsy, 51, 69, 223 Avian, 36, 60, 61, 62, 90, 100, 108, 123, 131, 132, 147, 151, 223 Azithromycin, 68, 73, 93, 94, 184, 188, 223 B Bacillus, 87, 223, 227 Back Pain, 140, 224 Bacteremia, 176, 224 Bacterial Infections, 47, 60, 137, 203, 224, 230, 261 Bacterial Physiology, 215, 224 Bactericidal, 224, 244 Bacteriophage, 224, 277, 296, 299 Bacteriostatic, 55, 224, 244 Bacterium, 224, 268 Bacteriuria, 176, 224 Basal Ganglia, 224, 231 Base, 32, 130, 215, 224, 237, 238, 244, 248, 259, 265, 293 Basement Membrane, 47, 224, 245, 260 Basophils, 50, 143, 224, 250, 260 Benign, 139, 224, 251, 269, 283 Benzene, 224, 253
Index 303
Beta-Thromboglobulin, 224, 257 Bilateral, 225, 244 Bile, 225, 247, 248, 259, 261 Bile Acids, 225, 248 Bile Pigments, 225, 259 Biliary, 225, 232 Bioassays, 24, 225 Bioavailability, 23, 153, 159, 225 Biochemical, 13, 23, 27, 29, 32, 33, 37, 43, 49, 52, 134, 218, 225, 227, 240, 250, 260, 272 Biogenesis, 14, 225 Biological Factors, 36, 225 Biological therapy, 225, 250 Biological Transport, 225, 239 Biomarkers, 23, 225 Biopsy, 90, 203, 225 Biopsy specimen, 90, 225 Biosynthesis, 36, 225, 276, 281, 288 Biotechnology, 60, 62, 173, 184, 195, 225 Biotransformation, 225 Biotype, 41, 226 Bisoprolol, 80, 226 Bladder, 23, 139, 226, 237, 256, 267, 281, 297 Bloating, 226, 256, 259 Blood Coagulation, 226, 228, 294 Blood Glucose, 170, 226, 252, 257 Blood pressure, 31, 144, 180, 226, 228, 229, 254, 266, 275, 282, 290 Blood Viscosity, 110, 226 Blood Volume, 110, 226 Blot, 41, 226 Body Fluids, 225, 226, 240, 290, 296 Body Mass Index, 92, 226 Bone Density, 185, 226 Bone Marrow, 39, 54, 67, 224, 226, 237, 250, 255, 262, 290, 291, 292 Bone Marrow Transplantation, 67, 226 Bone metastases, 226, 233 Bone Resorption, 162, 226 Bowel, 219, 226, 239, 256, 260, 275, 291, 297 Bowel Movement, 226, 239, 291 Brachytherapy, 227, 258, 283, 300 Bradykinin, 49, 227, 259, 270, 277 Branch, 46, 54, 211, 227, 241, 248, 255, 262, 274, 282, 290, 294 Breakdown, 135, 227, 239, 247 Broad-spectrum, 72, 75, 219, 227, 229, 230 Bronchi, 137, 154, 227, 244, 245, 296 Bronchial Hyperreactivity, 59, 227
Bronchiectasis, 15, 29, 35, 50, 52, 57, 73, 144, 152, 160, 166, 177, 180, 227 Bronchioles, 137, 154, 218, 227, 282 Bronchiolitis, 17, 19, 20, 35, 47, 90, 144, 165, 200, 201, 227 Bronchiolitis Obliterans, 19, 20, 35, 165, 227 Bronchiseptica, 55, 69, 227 Bronchoalveolar Lavage, 51, 91, 102, 227 Bronchoalveolar Lavage Fluid, 51, 91, 227 Bronchoconstriction, 11, 20, 26, 53, 227 Bronchodilator, 13, 44, 144, 227, 246 Bronchopulmonary, 11, 227 Bronchoscopy, 6, 84, 90, 203, 227 Bronchospasm, 58, 227 Bronchus, 227 Buccal, 228, 262 Budesonide, 88, 228 C Cachexia, 136, 228 Cadmium, 34, 228 Cadmium Poisoning, 228 Calcium, 23, 30, 228, 233, 234, 253, 258, 263, 268, 281, 289 Callus, 228, 259 Capillary, 227, 228, 282, 299 Capillary Permeability, 227, 228 Capsid, 133, 228, 271, 299 Captopril, 100, 228 Carbohydrate, 21, 154, 228, 236, 249, 250, 279 Carbon Dioxide, 151, 228, 238, 246, 247, 285, 298 Carcinogenesis, 23, 26, 228, 231 Carcinogenic, 43, 224, 228, 256, 271, 280 Carcinoma, 11, 228 Cardiac, 24, 31, 34, 125, 139, 163, 164, 220, 228, 242, 244, 254, 268, 286, 292 Cardiopulmonary, 26, 31, 125, 228 Cardioselective, 223, 226, 229, 280 Cardiotonic, 229, 276 Cardiovascular, 5, 12, 24, 31, 38, 80, 137, 143, 161, 163, 229, 293 Cardiovascular disease, 5, 31, 161, 229 Cardiovascular System, 143, 229 Carrier Proteins, 229, 277 Case report, 68, 94, 229, 246 Case series, 84, 229 Caspase, 61, 100, 229 Catarrh, 140, 229 Catechol, 162, 229 Catecholamines, 216, 229
304 Bronchitis
Cathepsins, 11, 229 Catheterization, 220, 229, 268 Cations, 229, 258 Causal, 229, 243, 288 Cause of Death, 4, 5, 42, 137, 145, 150, 229, 238 Cefaclor, 71, 229 Ceftazidime, 83, 229 Ceftriaxone, 74, 83, 229 Cefuroxime, 60, 71, 74, 82, 83, 230 Cell Adhesion, 24, 43, 230, 257 Cell Cycle, 59, 230 Cell Death, 43, 59, 222, 230, 249, 269 Cell Differentiation, 52, 230, 289 Cell Division, 224, 230, 250, 264, 266, 277, 280, 287 Cell membrane, 225, 229, 230, 238, 276 Cell proliferation, 37, 42, 59, 73, 141, 230, 257, 289 Cell Respiration, 230, 285 Cell Survival, 51, 59, 230, 250 Cell Transplantation, 230 Cellulose, 230, 277 Central Nervous System, 159, 215, 217, 223, 224, 230, 247, 249, 251, 260, 267, 270, 293 Central Nervous System Infections, 230, 251 Cephalexin, 229, 230 Cephaloridine, 229, 230 Cerebral, 162, 163, 164, 224, 230, 231, 235, 244, 290, 293, 296 Cerebral Hemorrhage, 163, 164, 230 Cerebral Infarction, 231 Cerebral Palsy, 231, 290 Cerebrospinal, 231, 289 Cerebrospinal fluid, 231, 289 Cerebrovascular, 229, 231 Cerebrum, 230, 231 Cervical, 4, 156, 231 Cervix, 231 Character, 220, 231, 238 Chemokines, 20, 24, 39, 50, 58, 141, 231 Chemoprevention, 28, 231 Chemopreventive, 28, 231 Chemotactic Factors, 231, 234, 270 Chemotaxis, 33, 63, 141, 231 Chemotherapy, 68, 71, 74, 75, 83, 88, 90, 91, 107, 109, 143, 173, 175, 231, 261 Chest Pain, 5, 203, 231 Chest wall, 107, 231, 286 Chlorine, 231, 254
Cholecystitis, 4, 232 Cholera, 57, 232, 288, 299 Cholestasis, 180, 232 Cholesterol, 155, 225, 232, 236, 261 Cholesterol Esters, 155, 232, 261 Choline, 43, 215, 232 Cholinergic, 10, 232, 270 Chromatin, 222, 232 Chromic, 8, 232 Chromium, 232 Chromosomal, 13, 219, 232, 277 Chromosome, 18, 32, 232, 251, 261, 287, 296 Chronic Disease, 18, 38, 169, 174, 180, 181, 228, 232 Chymopapain, 232, 273 Chymotrypsin, 11, 135, 156, 217, 232 Ciliary, 16, 30, 32, 55, 145, 149, 150, 232, 267 Ciprofloxacin, 48, 61, 88, 232 CIS, 36, 60, 138, 157, 232, 286 Clamp, 43, 232 Clarithromycin, 63, 65, 71, 77, 82, 84, 233 Claudication, 21, 233 Clavulanic Acid, 63, 233 Clear cell carcinoma, 233, 239 Cleave, 37, 233 Clinical trial, 7, 8, 74, 125, 127, 138, 158, 195, 233, 235, 237, 267, 281, 283, 284 Clitoral, 140, 164, 233 Clodronate, 86, 233 Cloning, 18, 24, 43, 225, 233 Coagulation, 166, 226, 233, 234, 252, 277, 294 Coal, 34, 171, 224, 233 Cobalt, 23, 233 Coculture, 29, 233 Codons, 131, 233, 248 Cofactor, 233, 281, 288, 294 Cohort Studies, 26, 28, 77, 233, 243 Colitis, 234, 259 Collagen, 224, 234, 245, 246, 248, 263, 278, 280 Collapse, 47, 155, 219, 227, 234, 289 Colloidal, 7, 217, 234, 241 Complement, 28, 219, 234, 235, 248, 257, 263, 277, 288 Complement 1, 234, 288 Complement 1 Inactivators, 234, 288 Complementary and alternative medicine, 105, 121, 234 Complementary medicine, 105, 235
Index 305
Complete remission, 235, 285 Computational Biology, 195, 235 Concomitant, 44, 59, 159, 235 Confounding, 28, 235 Congestion, 235, 238, 244 Congestive heart failure, 139, 235 Conjunctiva, 235, 256 Conjunctivitis, 144, 235 Connective Tissue, 38, 226, 234, 235, 246, 247, 248, 250, 262, 264, 275, 286, 287, 292, 293 Connective Tissue Cells, 235 Consciousness, 219, 235, 238, 240, 286, 293 Constipation, 235, 259 Constriction, 10, 235, 259, 299 Consumption, 76, 235, 248, 271, 272 Continuum, 19, 235 Contractility, 24, 235 Contraindications, ii, 235 Control group, 5, 235 Controlled study, 6, 75, 107, 235 Convulsions, 235, 241, 280 Coordination, 25, 236, 267 Cornea, 236, 298 Corneal Ulcer, 135, 236 Corneum, 236, 243, 254 Coronary, 21, 139, 140, 161, 162, 163, 164, 185, 220, 229, 236, 265, 268 Coronary Arteriosclerosis, 236, 268 Coronary Artery Bypass, 163, 164, 236 Coronary Circulation, 220, 236 Coronary heart disease, 21, 229, 236 Coronary Thrombosis, 236, 265, 268 Coronavirus, 36, 60, 61, 62, 100, 142, 152, 236 Corpus, 236, 274 Cortical, 236, 245 Corticosteroid, 27, 73, 86, 236 Cortisone, 236, 239 Cranial, 236, 244, 246, 251, 273, 275, 290, 298 Craniocerebral Trauma, 231, 236, 251, 295 Creatinine, 5, 237 Creatinine clearance, 5, 237 Critical Care, 39, 64, 69, 72, 76, 79, 80, 82, 92, 101, 237 Crossing-over, 237, 284 Cross-Sectional Studies, 237, 243 Cryptosporidiosis, 223, 237 Culture Media, 216, 237 Cultured cells, 100, 237 Curative, 32, 237, 294
Cutaneous, 237, 259, 262 Cyclic, 139, 163, 237, 250, 270, 276 Cyclosporine, 8, 165, 237 Cysteine, 11, 49, 61, 99, 101, 115, 119, 134, 215, 231, 232, 237, 240, 242, 292 Cystine, 237, 240 Cystitis, 16, 176, 237 Cytidine, 145, 237 Cytokine, 18, 20, 24, 27, 30, 33, 34, 53, 58, 91, 141, 237, 257, 274 Cytomegalovirus, 5, 196, 203, 237 Cytoplasm, 222, 224, 230, 237, 238, 243, 250, 287 Cytosine, 237, 238 Cytoskeleton, 24, 238, 257 Cytotoxic, 50, 62, 217, 238, 254, 255, 283, 289 Cytotoxicity, 153, 238 D Databases, Bibliographic, 195, 238 Death Certificates, 5, 238 Decarboxylation, 238, 253 Decision Making, 40, 77, 238 Decongestant, 134, 238, 276 Defense Mechanisms, 238, 257 Degenerative, 238, 252, 272, 286 Dehydration, 57, 232, 238 Deletion, 19, 54, 146, 222, 238 Dementia, 5, 139, 238 Denaturation, 238, 279 Dendrites, 238, 270 Dendritic, 238, 264 Density, 10, 12, 22, 226, 238, 261, 271 Dental Care, 177, 238 Dentists, 4, 238 Depolarization, 238, 289 Dermatitis, 7, 135, 136, 144, 163, 238, 241 Dermatology, 25, 239 DES, 143, 219, 239 Desensitization, 30, 43, 50, 239 Desquamation, 59, 239 Deuterium, 239, 253 Dexamethasone, 27, 239 Diabetes Mellitus, 4, 136, 239, 249, 252 Diagnostic procedure, 85, 129, 185, 239 Diaphragm, 239, 286 Diarrhea, 57, 152, 237, 239, 259 Diarrhoea, 239, 248 Diastolic, 239, 254 Diffusion, 106, 151, 225, 228, 239, 255, 256, 270
306 Bronchitis
Digestion, 225, 226, 239, 241, 256, 261, 291, 298 Digestive system, 127, 176, 185, 239, 267 Dihydrotestosterone, 239, 284 Dilatation, 220, 227, 239, 258, 280, 282, 298 Dilatation, Pathologic, 239, 298 Dilation, 140, 164, 180, 223, 227, 239, 298 Diploid, 239, 277 Direct, iii, 14, 20, 26, 29, 36, 38, 43, 48, 157, 187, 239, 284, 293 Disease Progression, 90, 239 Disinfectant, 240, 244 Dissociation, 216, 240 Distal, 137, 140, 164, 236, 240, 248, 282 Disulphide, 154, 240 Dithiothreitol, 73, 240 Domesticated, 142, 240, 250 Dominance, 78, 240 Dose-rate, 26, 240 Drip, 6, 240 Drug Interactions, 190, 240 Drug Tolerance, 240, 295 Drug Toxicity, 8, 240 Dry Eye Syndrome, 57, 240 Duct, 219, 229, 240, 245, 273, 287, 293 Ductus Arteriosus, 240 Duodenum, 225, 232, 240, 273, 291 Dura mater, 240, 264, 273 Dyes, 219, 224, 240 Dyskinesia, 32, 145, 149, 150, 240 Dysmenorrhea, 164, 241 Dysmenorrhoea, 139, 241 Dyspepsia, 241, 256 Dyspnea, 102, 111, 241, 282 E Eclampsia, 164, 224, 241, 280 Eczema, 175, 241 Edema, 7, 12, 58, 139, 231, 234, 241, 267, 268, 280 Effector, 29, 215, 234, 241, 270, 276 Elasticity, 43, 236, 241 Elastin, 234, 241, 245, 260 Electrocoagulation, 233, 241 Electrolyte, 236, 241, 265, 290 Electron microscope, 241, 269 Electrons, 221, 224, 241, 258, 269, 272, 283 Electrophoresis, 33, 241, 255 Electroplating, 229, 241 Embryo, 230, 241, 256, 278 Emergency Medicine, 65, 75, 86, 241 Emergency Treatment, 241 Emesis, 160, 241
Emollient, 241, 249, 265, 271 Empirical, 93, 242 Emulsions, 217, 242 Encapsulated, 14, 242 Endarterectomy, 163, 164, 220, 223, 242 Endemic, 151, 232, 242, 291 Endocarditis, 14, 242 Endocardium, 242, 297 Endocytosis, 45, 242 Endometrial, 242 Endometriosis, 166, 242 Endometrium, 242 Endopeptidases, 229, 242, 281, 288 Endoscopy, 5, 242 Endothelial cell, 12, 43, 56, 242, 257, 294, 297 Endothelium, 16, 139, 143, 163, 164, 242, 243, 270, 278, 297 Endothelium, Lymphatic, 242 Endothelium, Vascular, 242 Endothelium-derived, 139, 163, 164, 243, 270 Endotoxic, 162, 243 Endotoxin, 9, 17, 22, 31, 36, 45, 149, 243, 297 Enteropeptidase, 243, 296 Environmental Exposure, 31, 34, 243 Environmental Health, 26, 42, 76, 89, 125, 194, 196, 243 Environmental Microbiology, 22, 243 Enzymatic, 55, 146, 228, 234, 243, 253, 273, 279, 286 Enzyme Inhibitors, 243, 277 Eosinophil, 76, 243, 257 Eosinophilia, 20, 55, 69, 76, 243 Eosinophilic, 20, 27, 70, 71, 74, 75, 79, 91, 243 Epidemics, 26, 243 Epidemiologic Studies, 31, 53, 243 Epidemiological, 76, 243, 246 Epidermal, 37, 42, 243, 259, 264 Epidermal Growth Factor, 37, 42, 243 Epidermis, 236, 243, 254, 259, 280 Epigastric, 243, 273 Epinephrine, 216, 243, 271, 297 Epithelium, 11, 14, 16, 20, 29, 30, 32, 37, 38, 42, 45, 52, 55, 58, 59, 85, 133, 155, 224, 242, 244 Epitopes, 41, 60, 244 Erectile, 140, 244, 274 Erection, 140, 164, 244 Erythema, 7, 21, 244, 298
Index 307
Erythema Nodosum, 21, 244 Erythrocyte Volume, 226, 244 Erythrocytes, 41, 80, 100, 219, 220, 226, 244, 284, 288 Erythromycin, 223, 233, 244 Esophageal, 244, 248 Esophagitis, 43, 244, 248 Esophagus, 26, 43, 177, 202, 239, 244, 248, 251, 262, 276, 284, 291 Ethanol, 30, 244 Ethmoid, 244, 273 Eukaryotic Cells, 244, 255, 272 Excipients, 130, 244 Excitatory, 10, 245, 249 Excitatory Amino Acids, 10, 245 Exfoliation, 239, 245 Exhaustion, 220, 245 Exocrine, 245, 273 Exogenous, 11, 35, 49, 149, 216, 225, 228, 241, 245, 250, 288 Exotoxin, 10, 245 Expectorant, 134, 147, 245 Expiration, 108, 150, 155, 245, 285 Expiratory, 44, 108, 245 Extensor, 245, 282 External-beam radiation, 245, 258, 283, 300 Extracellular, 19, 37, 49, 135, 219, 223, 235, 242, 245, 246, 257, 263, 265, 290 Extracellular Matrix, 19, 37, 235, 245, 246, 257, 263 Extracellular Matrix Proteins, 245, 263 Extracellular Space, 245, 265 Extravasation, 143, 245 Extravascular, 54, 245 Extremity, 14, 176, 245 Exudate, 227, 245 F Facial, 245, 246, 273 Facial Nerve, 246, 273 Failure to Thrive, 180, 246 Family Planning, 195, 246 Fat, 180, 216, 220, 226, 236, 246, 261, 267, 286, 290, 292 Fatal Outcome, 246, 283 Fatigue, 203, 213, 246, 251 Fatty acids, 217, 246, 249, 261 Febrile, 5, 246 Fenoterol, 99, 246 Fetus, 246, 298 Fibrin, 221, 226, 246, 278, 294, 295 Fibrinogen, 31, 246, 277, 278, 294
Fibroblasts, 235, 246, 257, 266 Filarioidea, 246, 259 Fixation, 246, 288 Flatus, 247 Fleroxacin, 61, 109, 247 Fluorescence, 57, 247 Fold, 21, 141, 146, 247, 264, 272 Foramen, 247, 275 Forearm, 226, 247 Formulary, 25, 77, 247 Friction, 217, 247, 262 Fungi, 22, 156, 247, 265, 266, 300 G Gallbladder, 133, 215, 225, 232, 239, 247 Gallic Acid, 134, 147, 247 Gamma-interferon, 247, 257 Ganglia, 215, 247, 269, 275 Ganglioside, 41, 247 Gangrene, 176, 247 Gangrenous, 247, 288 Gas exchange, 15, 247, 282, 285, 286, 298 Gastric, 219, 243, 247, 248, 251, 253 Gastric Acid, 219, 247 Gastrin, 247, 253 Gastroenteritis, 5, 99, 101, 247 Gastroesophageal Reflux, 5, 6, 177, 248 Gastroesophageal Reflux Disease, 5, 177, 248 Gastrointestinal tract, 153, 166, 244, 248, 296 Gelatin, 237, 248, 249, 294 Gels, 154, 248 Gene Expression, 15, 30, 38, 45, 52, 76, 80, 133, 154, 248 General practitioner, 93, 248 Generator, 23, 248 Genetic Code, 248, 271 Genetic Engineering, 225, 233, 248 Genetic Markers, 22, 43, 248 Genetic testing, 248, 279 Genetics, 18, 21, 31, 35, 62, 77, 151, 240, 248, 255 Genital, 140, 164, 232, 233, 248, 297, 299 Genitourinary, 248, 293, 297 Genotype, 17, 18, 226, 249, 276 Giant Cells, 249, 287 Gland, 10, 15, 37, 175, 216, 236, 249, 262, 263, 273, 277, 281, 287, 291, 292, 293, 294 Glioma, 161, 249 Glomerular, 249, 285 Glomeruli, 249, 283 Glomerulonephritis, 135, 249
308 Bronchitis
Glomerulus, 249, 269 Glucocorticoid, 228, 239, 249 Glucose, 147, 170, 226, 230, 232, 239, 249, 252, 257, 284 Glucose Intolerance, 239, 249 Glucuronic Acid, 249, 252 Glutamic Acid, 249, 280 Glycerol, 155, 249, 276 Glycerophospholipids, 249, 276 Glycine, 153, 249, 288 Glycoprotein, 101, 106, 133, 161, 167, 217, 218, 221, 234, 246, 249, 250, 260, 267, 294, 296 Glycosidic, 155, 249, 269, 271 Glycosylation, 154, 250 Goblet Cells, 35, 137, 152, 153, 154, 250 Gonorrhea, 230, 250 Governing Board, 250, 279 Gp120, 250, 274 Graft, 5, 8, 20, 56, 136, 164, 165, 250, 253, 255, 268 Graft Rejection, 164, 165, 250, 255 Grafting, 141, 236, 250 Graft-versus-host disease, 250, 268 Gram-negative, 14, 17, 32, 227, 229, 230, 243, 250, 251, 282, 299 Gram-Negative Bacteria, 14, 17, 32, 243, 250 Gram-positive, 230, 250, 268, 291 Granulation Tissue, 227, 250 Granulocytes, 250, 260, 289, 300 Growth factors, 12, 141, 250 Growth Inhibitors, 141, 250 Guanylate Cyclase, 250, 270 Guinea Pigs, 54, 98, 250 Gyrase, 247, 251 H Habitat, 251, 268 Haematemesis, 241, 251 Haemophilus, 14, 29, 41, 64, 77, 82, 230, 251 Haemophilus influenzae, 14, 29, 41, 64, 77, 82, 251 Hair follicles, 251, 299 Half-Life, 49, 229, 251 Haploid, 251, 277 Haplotypes, 18, 251 Haptens, 216, 251 Headache, 140, 218, 251, 256 Headache Disorders, 251 Health Services, 14, 174, 251 Health Status, 4, 13, 93, 251
Healthy Worker Effect, 26, 251 Heart attack, 162, 229, 251 Heart failure, 251, 282 Heartbeat, 251, 292 Heartburn, 5, 251, 256 Hematopoiesis, 251, 257 Hematopoietic growth factors, 29, 251 Heme, 56, 149, 252, 272 Hemoglobin, 220, 244, 252, 272 Hemorrhage, 237, 241, 251, 252, 268, 292 Hemostasis, 161, 252, 257 Heparin, 45, 50, 99, 252, 278, 288 Hepatic, 139, 217, 252 Hepatitis, 180, 252 Hepatocellular, 180, 252 Hepatocellular carcinoma, 180, 252 Hepatocyte, 232, 252 Hereditary, 218, 234, 252, 286 Heredity, 215, 248, 252 Hernia, 4, 252 Herpes, 5, 133, 252 Herpes Zoster, 5, 252 Heterodimers, 252, 257 Heterogeneity, 94, 216, 252 Heterotrophic, 247, 252 Heterozygotes, 240, 252 Histamine, 160, 219, 253 Histidine, 135, 253 Hoarseness, 5, 177, 253, 260 Homeostasis, 49, 56, 149, 253 Homogeneous, 235, 253 Homologous, 133, 237, 252, 253, 267, 287, 288, 293, 296 Homozygotes, 240, 253 Hormonal, 140, 164, 223, 236, 253 Hormone, 52, 171, 217, 225, 236, 239, 243, 247, 253, 257, 264, 286, 289, 294 Host, 14, 17, 21, 27, 30, 41, 47, 49, 59, 131, 136, 147, 152, 224, 253, 254, 255, 266, 267, 298, 299 Humoral, 250, 253 Hybrid, 253 Hybridization, 24, 253 Hydration, 16, 145, 253 Hydrogen Peroxide, 149, 253, 261 Hydrolysis, 215, 226, 253, 260, 269, 276, 279, 281, 296 Hydroxybenzoic Acids, 134, 147, 253 Hyperaemia, 235, 253 Hyperbilirubinemia, 253, 259 Hypercalcemia, 233, 253 Hyperglycemia, 170, 253
Index 309
Hyperoxia, 149, 254 Hyperplasia, 15, 37, 38, 59, 137, 254 Hypersecretion, 34, 35, 37, 42, 45, 52, 133, 152, 254 Hypersensitivity, 9, 11, 217, 219, 239, 243, 254, 286, 288 Hypertension, 139, 148, 164, 180, 226, 229, 231, 251, 254, 280, 281, 295 Hypertension, Pulmonary, 139, 254 Hypertrophy, 15, 37, 137, 254 Hypochlorous Acid, 135, 254 Hypoglycemia, 170, 254 Hypothalamus, 223, 254, 277 Hypoventilation, 8, 254 Hypoxemia, 48, 254 Hypoxia, 254 I Ichthyosis, 144, 254 Id, 103, 111, 143, 200, 203, 204, 210, 212, 254 Idiopathic, 47, 148, 165, 254, 287 Immune function, 254, 255 Immune Sera, 254 Immune system, 33, 36, 221, 225, 254, 255, 262, 263, 267, 268, 298, 300 Immune-response, 33, 254 Immunity, 18, 33, 35, 100, 101, 161, 217, 254, 255, 296 Immunization, 51, 132, 216, 254, 255, 280, 288 Immunocompromised, 67, 255 Immunodeficiency, 98, 139, 203, 255 Immunodiffusion, 217, 255 Immunoelectrophoresis, 217, 221, 255 Immunogenetics, 35, 255 Immunogenic, 41, 255 Immunoglobulin, 16, 221, 255, 266 Immunohistochemistry, 39, 43, 58, 255 Immunologic, 176, 216, 218, 231, 254, 255, 274, 283 Immunology, 18, 20, 35, 38, 39, 47, 65, 70, 77, 90, 91, 100, 216, 255 Immunosuppressive, 8, 165, 249, 255, 293 Immunosuppressive Agents, 165, 255 Immunosuppressive therapy, 255 Immunotherapy, 20, 56, 216, 225, 239, 255 Impairment, 22, 34, 133, 232, 240, 255, 264, 280 Implant radiation, 255, 258, 283, 300 Impotence, 171, 172, 244, 255 In situ, 11, 43, 59, 255 In Situ Hybridization, 43, 59, 255
Incision, 256, 258, 292 Incompetence, 248, 256 Incontinence, 139, 140, 256 Indicative, 170, 256, 274, 298 Indigestion, 196, 256 Induction, 18, 26, 29, 45, 54, 55, 56, 59, 61, 100, 145, 149, 219, 256 Infarction, 231, 256, 258, 285 Infectious Bursal Disease Virus, 131, 132, 147, 256 Infiltration, 52, 249, 256, 260 Inflammatory bowel disease, 136, 160, 162, 256 Influenza, 140, 156, 176, 256 Ingestion, 30, 228, 256, 278 Inhalation, 8, 22, 23, 34, 45, 53, 56, 65, 80, 137, 177, 188, 216, 227, 256, 258, 278 Inhalation Exposure, 34, 53, 256 Initiation, 37, 47, 256, 296 Inlay, 256, 286 Inner ear, 230, 256 Inorganic, 22, 257, 267 Inositol, 10, 257 Inotropic, 223, 257 Insight, 12, 13, 19, 30, 33, 49, 54, 257 Instillation, 51, 137, 257 Insulator, 257, 267 Insulin, 6, 170, 257 Insulin-dependent diabetes mellitus, 257 Integrins, 29, 54, 257 Intercellular Adhesion Molecule-1, 29, 257 Intercellular Junctions, 12, 16, 257 Interleukin-4, 76, 80, 257 Interleukin-5, 76, 80, 257 Interleukin-8, 50, 257 Interleukins, 255, 257 Intermittent, 88, 240, 258 Internal radiation, 258, 283, 300 Interstitial, 47, 148, 227, 245, 258, 269, 285, 300 Intestines, 215, 247, 248, 258 Intracellular, 16, 30, 35, 36, 52, 53, 143, 163, 256, 257, 258, 264, 270, 289 Intracellular Membranes, 36, 258, 264 Intracranial Aneurysm, 231, 258 Intracranial Arteriosclerosis, 231, 258 Intraepithelial, 9, 45, 258 Intravascular, 258, 260 Intravenous, 165, 189, 196, 258 Intrinsic, 216, 224, 258 Invasive, 40, 41, 81, 254, 258, 272 Involuntary, 258, 268, 284
310 Bronchitis
Ion Channels, 223, 258, 270, 293 Ionizing, 218, 243, 258, 263, 283 Ions, 113, 167, 224, 234, 240, 241, 253, 258, 266, 281 Ipratropium, 99, 117, 188, 258 Irradiation, 23, 149, 258, 300 Irritable Bowel Syndrome, 139, 140, 259 Irritants, 51, 133, 259 Ischemia, 20, 24, 56, 162, 223, 247, 259, 268, 285 Isotretinoin, 138, 157, 259 Isozymes, 50, 77, 160, 259 Ivermectin, 99, 100, 259 J Jaundice, 180, 253, 259 Joint, 140, 162, 222, 232, 259, 272, 293 K Kallidin, 227, 259 Kb, 18, 194, 259 Keratin, 259 Keratinocytes, 43, 257, 259 Keratosis, 144, 259 Keto, 134, 259 Kidney Disease, 57, 127, 148, 176, 194, 259 Kidney stone, 259, 285, 297 Kinetic, 258, 260 L Labile, 234, 260 Laminin, 224, 245, 260 Large Intestine, 239, 258, 260, 284, 290 Laryngitis, 112, 156, 177, 260 Larynx, 148, 177, 202, 260, 296, 298 Latency, 26, 260 Latent, 40, 260, 280 Lavage, 24, 53, 58, 260 Laxative, 216, 260, 265 Lectin, 90, 260, 264 Lesion, 47, 143, 236, 260, 261, 289 Leucocyte, 243, 260 Leukemia, 50, 260, 261 Leukemic Infiltration, 260, 261 Leukocyte Elastase, 146, 260 Leukocytes, 29, 38, 46, 50, 58, 135, 143, 167, 224, 226, 231, 250, 257, 260, 266, 297 Leukostasis, 56, 260 Levofloxacin, 73, 82, 88, 96, 261 Library Services, 210, 261 Life cycle, 247, 261 Ligament, 261, 274, 281 Ligands, 16, 23, 39, 43, 257, 261 Linear Models, 26, 261 Linkage, 13, 18, 22, 25, 57, 77, 248, 261, 274
Lipid, 47, 53, 80, 100, 155, 228, 232, 242, 249, 257, 259, 261, 267, 272 Lipid Peroxidation, 53, 261, 272 Lipopolysaccharide, 32, 149, 250, 261 Lipoprotein, 250, 261, 299 Lipoxygenase, 77, 222, 261 Liver cancer, 180, 261 Localization, 22, 52, 123, 255, 261 Localized, 11, 14, 32, 135, 140, 164, 242, 246, 256, 260, 261, 268, 277, 298 Locomotion, 261, 277 Longitudinal study, 14, 61, 80, 261 Loop, 252, 262 Lower Esophageal Sphincter, 248, 262 Lubricants, 262, 275 Lubrication, 140, 164, 262 Lumbar, 224, 262 Lumen, 15, 154, 242, 262 Lung Transplantation, 8, 17, 20, 46, 56, 165, 262 Lung volume, 13, 262, 286 Lupus, 81, 162, 185, 262, 293 Lymph, 231, 242, 262, 287, 292 Lymph node, 231, 262, 287 Lymphadenitis, 262, 268 Lymphatic, 242, 256, 262, 264, 290, 291, 294 Lymphatic system, 262, 290, 291, 294 Lymphocyte, 8, 58, 221, 262, 263, 264, 266 Lymphocytic, 47, 260, 262 Lymphoid, 15, 221, 250, 254, 260, 262 Lymphoma, 203, 262 Lysine, 262, 296 Lysosome, 21, 262 Lyssavirus, 263, 283 Lytic, 263, 299 M Macrolides, 94, 263 Macrophage, 23, 33, 34, 39, 43, 263 Major Histocompatibility Complex, 251, 257, 263 Malignant, 50, 135, 141, 176, 215, 221, 261, 263, 269, 283, 287 Malignant tumor, 135, 263 Malnutrition, 217, 223, 228, 263 Mammary, 236, 263 Mandible, 218, 263, 285 Manifest, 17, 58, 263 Man-made, 229, 263 Mass Media, 40, 263 Mastitis, 263, 288 Matrix metalloproteinase, 39, 263
Index 311
Maxillary, 263, 273 Meat, 142, 263 Mechanical ventilation, 109, 263 Mechanoreceptors, 263, 286 Mediate, 33, 50, 54, 60, 144, 263 Mediator, 9, 20, 29, 79, 141, 163, 264, 278 Medical Records, 264, 286 MEDLINE, 195, 264 Meiosis, 264, 267, 293 Melanin, 264, 276, 297 Melanocytes, 141, 264 Melanoma, 50, 141, 264 Melanosomes, 264 Membrane Proteins, 36, 264 Memory, 6, 58, 136, 177, 220, 238, 264 Meninges, 229, 230, 236, 240, 264 Meningitis, 14, 196, 264 Menstruation, 241, 264 Mental Disorders, 127, 264, 280, 282 Mental Health, iv, 7, 127, 194, 197, 264, 271, 280, 282 Mental Retardation, 6, 264 Mesenchymal, 243, 264 Mesenteric, 264, 279 Meta-Analysis, 25, 265 Metabolic disorder, 179, 265 Metabolite, 218, 225, 265, 280 Metaplasia, 37, 38, 45, 51, 153, 265 Metastasis, 141, 263, 265 Metastatic, 141, 265, 287 Methionine, 135, 265, 292 MI, 214, 265 Microbe, 265, 295 Microbiology, 22, 47, 69, 88, 101, 215, 224, 265 Microcirculation, 265, 278 Microdialysis, 11, 265 Microorganism, 233, 265, 273, 299 Micro-organism, 250, 265, 288 Microscopy, 11, 14, 24, 38, 39, 41, 49, 52, 224, 265 Migration, 16, 24, 39, 54, 101, 257, 265 Milliliter, 226, 265 Mineral Oil, 26, 265 Mineralocorticoids, 216, 236, 265 Mitochondrial Swelling, 266, 269 Mitosis, 222, 266 Mitosporic Fungi, 222, 266 Modeling, 26, 266 Modification, 248, 266, 283 Molecular mass, 14, 266 Molecular Structure, 153, 266
Monitor, 23, 67, 71, 237, 266, 271 Monoclonal, 16, 41, 54, 258, 266, 283, 300 Monoclonal antibodies, 16, 41, 54, 266 Monocular, 19, 266 Monocyte, 16, 19, 43, 266 Monocyte Chemoattractant Protein-1, 19, 266 Mononuclear, 19, 78, 266, 297 Monophosphate, 139, 266 Morphogenesis, 15, 267 Morphological, 37, 38, 241, 264, 267 Morphology, 39, 267 Motility, 27, 30, 43, 139, 140, 267 Mucins, 42, 45, 76, 133, 145, 153, 167, 250, 267, 287 Mucociliary, 16, 30, 32, 49, 51, 72, 99, 133, 137, 145, 167, 218, 267, 289 Mucociliary Clearance, 16, 30, 32, 49, 51, 72, 99, 137, 145, 267 Mucolytic, 81, 215, 227, 267 Mucosa, 12, 38, 77, 262, 267, 269, 292 Mucositis, 267, 294 Multicenter study, 46, 267 Multiple Organ Failure, 135, 267 Multiple sclerosis, 136, 267 Multivalent, 132, 267 Mustard Gas, 259, 267 Mutagenesis, 49, 267 Mutagens, 267 Myalgia, 256, 267 Mycobacteriosis, 267, 268 Mycobacterium, 203, 223, 267, 268, 296 Mycobacterium avium, 203, 223, 268 Mycobacterium avium Complex, 203, 268 Mycophenolate mofetil, 165, 268 Mydriatic, 239, 268, 276 Myelin, 267, 268 Myocardial infarction, 161, 163, 164, 224, 236, 265, 268, 281 Myocardial Ischemia, 135, 220, 268 Myocardial Reperfusion, 268, 285 Myocardial Reperfusion Injury, 268, 285 Myocardium, 220, 265, 268 N N-acetyl, 99, 101, 119, 155, 215, 268 Naive, 29, 268 Nasal Cavity, 269, 273 Nasal Mucosa, 256, 269 Natural selection, 225, 269 Nausea, 218, 248, 256, 269, 297 NCI, 1, 127, 193, 232, 269
312 Bronchitis
Necrosis, 47, 222, 231, 236, 256, 265, 268, 269, 285, 287, 288 Need, 3, 5, 21, 27, 69, 136, 137, 156, 169, 175, 179, 185, 196, 203, 205, 216, 262, 263, 269, 295 Negative Staining, 14, 269 Neoplasm, 269, 287, 297 Neoplastic, 219, 261, 262, 269 Nephritis, 152, 164, 269 Nephropathy, 259, 269 Nephrosis, 152, 269 Nephrotic, 139, 269 Nerve, 216, 220, 238, 246, 264, 267, 269, 273, 276, 279, 286, 287, 291, 295, 296, 298 Nervous System, 10, 130, 148, 216, 223, 230, 263, 264, 269, 270, 275, 283, 293 Networks, 167, 269 Neural, 216, 219, 253, 263, 269, 286 Neuraminidase, 269, 273 Neurologic, 269, 296 Neuromuscular, 215, 270 Neuromuscular Junction, 215, 270 Neuronal, 43, 270 Neurons, 10, 238, 245, 247, 270, 283, 293 Neuropathy, 166, 176, 270 Neuropeptide, 143, 270 Neuropsychological Tests, 6, 270 Neurosis, 270, 276 Neurotransmitters, 245, 266, 270 Neutrons, 218, 258, 270, 283 Neutrophil, 9, 16, 17, 24, 37, 41, 42, 43, 44, 54, 63, 98, 135, 141, 156, 218, 257, 270 Neutrophil Activation, 141, 270 Neutrophil Infiltration, 43, 270 Nicotine, 43, 202, 270 Nitric Oxide, 30, 53, 55, 65, 139, 163, 164, 270 Nitrogen, 217, 218, 219, 245, 246, 266, 271 Norepinephrine, 216, 271 Nosocomial, 82, 271, 282 Nuclear, 63, 224, 233, 241, 244, 263, 269, 271 Nucleic acid, 24, 153, 228, 238, 248, 253, 255, 267, 271, 283 Nucleic Acid Hybridization, 253, 271 Nucleocapsid, 62, 271 Nucleus, 10, 30, 222, 223, 224, 232, 237, 239, 244, 264, 266, 270, 271, 280, 281, 291 Nutritional Status, 3, 271 O Occupational Exposure, 6, 13, 31, 43, 271 Occupational Health, 24, 34, 271
Ointments, 271, 300 Oligosaccharides, 154, 269, 271 Oncogenic, 257, 271 Opacity, 238, 271 Operon, 271, 285 Opportunistic Infections, 165, 271 Oral Health, 3, 175, 272 Organ Culture, 272, 295 Organ Transplantation, 135, 272 Organelles, 237, 264, 272 Orgasm, 140, 164, 272 Osteoarthritis, 46, 136, 272 Osteoporosis, 86, 101, 136, 272 Otitis, 14, 32, 41, 47, 145, 176, 272 Otitis Media, 14, 32, 41, 47, 145, 272 Outpatient, 25, 47, 73, 108, 272 Ovalbumin, 51, 272, 288 Ovary, 272, 278, 292 Overexpress, 11, 272 Oxidation, 53, 215, 221, 222, 226, 237, 240, 261, 272 Oxidative Stress, 37, 53, 149, 272 Oximetry, 203, 272 Oxygen Consumption, 272, 285 Oxygenase, 56, 149, 272 Oxygenation, 254, 273 P Pachymeningitis, 264, 273 Palliative, 137, 273, 294 Pancreas, 26, 143, 175, 215, 225, 232, 239, 257, 273, 291, 296 Pancreatic, 46, 133, 232, 248, 273 Pancreatic Ducts, 133, 273 Pancreatic Juice, 232, 248, 273 Panniculitis, 180, 273 Papain, 61, 100, 273 Paralysis, 43, 273, 290 Paramyxovirus, 59, 273 Paranasal Sinuses, 145, 150, 273, 289 Parasite, 259, 273 Parasitic, 99, 100, 101, 237, 273 Parotid, 175, 273, 287 Paroxysmal, 220, 251, 273 Partial remission, 273, 285 Particle, 8, 22, 23, 26, 34, 53, 65, 263, 273, 296 Patch, 43, 273 Patent ductus arteriosus, 81, 273 Pathogen, 21, 55, 131, 147, 156, 273 Pathogenesis, 13, 14, 18, 19, 20, 21, 27, 30, 32, 33, 34, 44, 45, 47, 55, 58, 135, 273
Index 313
Pathologic, 41, 45, 222, 225, 236, 253, 254, 260, 274, 282, 285 Pathologic Processes, 222, 274 Pathologies, 55, 131, 147, 274 Pathophysiology, 4, 10, 15, 27, 36, 38, 176, 274 Patient Education, 40, 202, 208, 210, 214, 274 Patient Satisfaction, 78, 274 Peak flow, 31, 274 Pedigree, 18, 22, 274 Pelvic, 242, 274, 281 Penicillin, 40, 219, 220, 274 Penis, 140, 164, 274 Pentoxifylline, 98, 274 Peptide, 16, 35, 141, 143, 146, 153, 155, 233, 242, 243, 259, 274, 279, 281 Peptide Chain Elongation, 233, 274 Peptide T, 35, 143, 274 Perception, 177, 274 Pericardium, 274, 293 Periodontal Attachment Loss, 4, 274 Periodontal disease, 4, 135, 274, 275 Periodontal Ligament, 274, 275 Periodontitis, 274, 275 Peripheral blood, 46, 78, 87, 275 Peripheral Nervous System, 143, 275, 292 Peripheral Vascular Disease, 139, 140, 148, 275 Periplasm, 14, 275 Peritoneal, 50, 54, 222, 275 Peritoneal Cavity, 54, 222, 275 Peritoneum, 275 Petroleum, 265, 275 PH, 57, 78, 90, 95, 226, 275 Pharmaceutical Preparations, 166, 230, 244, 248, 275 Pharmacists, 25, 275 Pharmacodynamic, 84, 275 Pharmacokinetic, 84, 275 Pharmacologic, 24, 53, 220, 251, 275, 295 Pharyngitis, 40, 58, 276 Pharynx, 248, 256, 269, 276, 298 Phenotype, 10, 15, 18, 19, 76, 276 Phenylalanine, 276, 297 Phenylephrine, 134, 276 Phobia, 159, 276 Phobic Disorders, 276 Phosphodiesterase, 135, 136, 139, 162, 274, 276 Phosphodiesterase Inhibitors, 139, 276 Phospholipases, 276, 289
Phospholipids, 155, 246, 257, 261, 276 Phosphorus, 228, 276 Phosphorylated, 161, 222, 276 Phosphorylation, 10, 30, 42, 50, 54, 276 Photocoagulation, 233, 276 Phototransduction, 222, 276 Physical Examination, 203, 276 Physical Medicine, 106, 180, 181, 277 Physical Therapy, 106, 109, 277 Physiologic, 9, 11, 23, 31, 53, 217, 225, 251, 264, 277, 284, 285 Physiology, 9, 24, 38, 49, 63, 277 Pigment, 264, 277 Pilot study, 196, 277 Piperidines, 159, 277 Pitch, 177, 277 Pituitary Gland, 143, 236, 277 Pivampicillin, 68, 277 Plant Growth Regulators, 250, 277 Plants, 7, 217, 223, 228, 232, 249, 260, 267, 271, 277, 278, 282, 288, 295 Plaque, 162, 220, 223, 277 Plasma cells, 221, 250, 277 Plasma protein, 146, 217, 242, 277, 281 Plasma Volume, 226, 266, 277 Plasmid, 131, 147, 277, 298 Plasmin, 221, 277, 278, 295, 297 Plasminogen, 45, 56, 166, 221, 277, 278, 288, 295, 297 Plasminogen Activators, 45, 166, 277, 278 Plasminogen Inactivators, 278, 288 Platelet Activation, 161, 278, 289 Platelet Aggregation, 164, 219, 270, 274, 278 Platelet Factor 4, 257, 278 Platelets, 143, 161, 222, 224, 270, 278, 294 Platyhelminths, 259, 278 Pleated, 141, 219, 259, 278 Pneumonectomy, 90, 278 Pneumonitis, 7, 228, 278 Poisoning, 228, 240, 248, 269, 278, 288 Pollen, 49, 278 Polymerase, 151, 278, 285 Polymerase Chain Reaction, 151, 278 Polymers, 134, 147, 154, 167, 279, 281 Polymorphic, 13, 279 Polymorphism, 17, 46, 151, 279 Polypeptide, 61, 62, 132, 153, 218, 234, 243, 246, 253, 277, 279, 281, 300 Polysaccharide, 166, 167, 221, 230, 279, 281 Port, 44, 279 Port-a-cath, 279
314 Bronchitis
Portal Vein, 180, 279 Posterior, 219, 224, 273, 279, 290 Postmenopausal, 272, 279 Postnatal, 279, 291 Postoperative, 267, 279 Postsynaptic, 279, 289, 293 Post-synaptic, 144, 279 Potentiates, 144, 279 Potentiating, 56, 166, 279 Potentiation, 279, 289 Practice Guidelines, 40, 197, 203, 279 Precancerous, 231, 279 Precipitating Factors, 4, 251, 280 Precursor, 220, 232, 241, 243, 271, 276, 278, 280, 281, 297 Predisposition, 13, 144, 280 Preeclampsia, 164, 280 Pre-eclamptic, 241, 280 Prevalence, 4, 13, 19, 28, 57, 70, 85, 86, 95, 99, 174, 175, 176, 243, 280 Preventive Medicine, 196, 209, 280 Prickle, 259, 280 Primary Prevention, 81, 280 Probe, 9, 265, 280 Probenecid, 71, 280 Prodrug, 46, 280 Progression, 13, 28, 36, 55, 137, 151, 220, 280 Progressive, 22, 44, 145, 165, 230, 236, 238, 240, 250, 267, 269, 272, 278, 280, 282, 285, 297 Proline, 153, 234, 280 Promoter, 11, 15, 17, 29, 131, 132, 280 Prophase, 267, 280, 293 Prophylaxis, 99, 153, 166, 280, 298 Propranolol, 223, 280 Prospective study, 70, 170, 261, 281 Prostate, 133, 161, 225, 281, 296 Protease, 13, 39, 42, 45, 49, 134, 135, 156, 166, 218, 278, 281, 295 Protease Inhibitors, 134, 156, 281 Protein C, 14, 50, 143, 155, 217, 218, 224, 259, 261, 281, 297, 299 Protein Conformation, 218, 259, 281 Protein Kinases, 30, 52, 281 Protein S, 24, 130, 148, 166, 173, 225, 233, 244, 248, 281, 287, 294 Proteinuria, 280, 281 Proteoglycans, 224, 245, 281 Proteolytic, 49, 61, 135, 218, 234, 243, 246, 273, 278, 281, 288, 295, 297 Prothrombin, 281, 294
Protocol, 8, 281 Protons, 218, 253, 258, 281, 283 Protozoa, 259, 265, 281 Proximal, 140, 164, 240, 269, 282 Pruritic, 241, 282 Pseudomonas, 41, 61, 98, 133, 229, 282 Pseudomonas aeruginosa, 41, 61, 98, 282 Psoriasis, 37, 135, 136, 144, 162, 163, 166, 267, 282 Psychiatry, 246, 282, 298 Psychotropic, 6, 282 Public Health, 21, 26, 27, 28, 31, 40, 48, 53, 80, 140, 164, 180, 181, 196, 197, 282 Public Policy, 195, 282 Publishing, 60, 169, 282 Pulmonary Alveoli, 254, 282 Pulmonary Artery, 226, 240, 273, 282 Pulmonary Circulation, 110, 254, 282 Pulmonary Embolism, 148, 163, 164, 282 Pulmonary Emphysema, 37, 126, 146, 162, 172, 174, 175, 180, 181, 218, 282 Pulmonary Fibrosis, 18, 23, 165, 282 Pulmonary hypertension, 100, 148, 282 Pulmonary Ventilation, 282, 286 Pulse, 266, 272, 282 Pupil, 236, 239, 268, 283 Purines, 283, 288 Purulent, 98, 283 Putrefaction, 247, 283 Pyelonephritis, 16, 176, 283 Q Quality of Life, 14, 44, 67, 95, 157, 180, 283, 292 R Rabies, 44, 263, 283 Rabies Virus, 44, 263, 283 Race, 4, 265, 283 Radiation, 22, 141, 220, 243, 245, 247, 258, 263, 283, 300 Radiation therapy, 245, 258, 283, 300 Radioactive, 251, 253, 255, 258, 263, 266, 267, 271, 283, 300 Radiolabeled, 258, 283, 300 Radiopharmaceutical, 248, 283 Radiotherapy, 227, 259, 283, 300 Randomized, 28, 44, 46, 47, 58, 63, 65, 66, 80, 82, 84, 88, 92, 241, 283, 284 Randomized Controlled Trials, 47, 284 Reabsorption, 280, 284 Reactivation, 176, 284 Reactive Oxygen Species, 24, 37, 53, 284 Reagent, 231, 240, 247, 284
Index 315
Recombinant, 15, 43, 131, 132, 153, 284, 298 Recombination, 123, 132, 248, 284 Reconstitution, 56, 284 Rectum, 154, 221, 226, 239, 247, 256, 260, 281, 284 Recurrence, 144, 231, 284 Red blood cells, 244, 273, 284 Reductase, 133, 284 Refer, 1, 228, 234, 246, 247, 252, 261, 262, 268, 270, 271, 284, 290 Reflex, 11, 284, 286 Reflux, 5, 6, 67, 248, 284 Refraction, 284, 290 Refractory, 8, 165, 241, 284 Regeneration, 38, 284 Regimen, 8, 241, 284 Regurgitation, 248, 251, 285 Relapse, 76, 285 Remission, 9, 145, 284, 285 Renal failure, 57, 139, 285 Renal tubular, 280, 285 Renin, 163, 164, 220, 228, 285 Renin-Angiotensin System, 228, 285 Reperfusion, 20, 56, 135, 162, 268, 285 Reperfusion Injury, 20, 135, 162, 285 Repressor, 30, 271, 285 Resorption, 159, 284, 285 Respirable, 31, 34, 285 Respiration, 82, 88, 99, 100, 107, 108, 144, 171, 222, 228, 266, 285, 286 Respirator, 263, 285, 298 Respiratory distress syndrome, 41, 135, 146, 148, 155, 285 Respiratory failure, 67, 165, 285, 298 Respiratory Mechanics, 24, 286 Respiratory Mucosa, 14, 29, 58, 286 Respiratory Physiology, 69, 70, 76, 82, 85, 86, 90, 92, 95, 108, 286, 298 Respiratory syncytial virus, 26, 58, 59, 286 Respiratory System, 177, 201, 217, 267, 286 Restoration, 39, 268, 277, 284, 285, 286, 300 Resuscitation, 241, 286 Retina, 276, 286, 287, 298 Retinal, 222, 266, 276, 286 Retinoblastoma, 59, 286 Retinoid, 138, 158, 286 Retinol, 138, 158, 286 Retinopathy, 166, 276, 286 Retrospective, 3, 28, 286 Retrospective study, 3, 286 Rheology, 274, 286
Rheumatism, 286 Rheumatoid, 37, 46, 50, 136, 146, 166, 286 Rheumatoid arthritis, 37, 46, 50, 136, 146, 166, 286 Rhinitis, 32, 79, 91, 130, 143, 160, 177, 227, 258, 287, 288 Ribose, 215, 237, 287 Ribosome, 287, 296 Rigidity, 277, 287 Risk factor, 13, 17, 31, 83, 85, 165, 180, 196, 243, 281, 287 Risk patient, 83, 287 Rod, 117, 223, 224, 232, 251, 282, 287 Rural Population, 174, 175, 287 S Saline, 44, 227, 287 Saliva, 283, 287 Salivary, 237, 239, 246, 287, 292 Salivary glands, 237, 239, 246, 287 Saphenous, 236, 287 Saphenous Vein, 236, 287 Sarcoidosis, 21, 287 Sarcoma, 203, 287 Schizophrenia, 138, 158, 287 Sclerosis, 258, 267, 287 Screening, 6, 44, 180, 233, 287 Sebaceous, 259, 287, 299 Sebaceous gland, 259, 287, 299 Secondary tumor, 265, 287 Secretory, 9, 35, 36, 45, 46, 153, 156, 267, 287, 293 Segregation, 22, 224, 284, 287 Sella, 277, 288 Semen, 281, 288 Semisynthetic, 219, 229, 230, 233, 259, 288 Senile, 110, 272, 288 Sensitization, 26, 288 Sensor, 10, 56, 288 Sepsis, 5, 17, 136, 148, 288 Septic, 135, 136, 149, 163, 288 Septicaemia, 288 Septicemia, 14, 288 Sequence Homology, 274, 288 Sequencing, 43, 133, 279, 288 Sequester, 45, 288 Serine, 11, 37, 44, 50, 134, 135, 146, 153, 232, 242, 288, 295, 296 Serine Endopeptidases, 242, 288 Serine Proteinase Inhibitors, 288 Serotypes, 151, 288 Serous, 242, 288 Serpins, 11, 50, 288
316 Bronchitis
Serum, 5, 17, 27, 31, 42, 90, 102, 144, 216, 217, 219, 234, 254, 266, 284, 288, 289, 296 Shedding, 239, 289 Shock, 78, 98, 135, 136, 149, 162, 163, 164, 219, 289, 296 Shunt, 5, 289 Side effect, 16, 137, 144, 187, 216, 225, 289, 292, 295 Signal Transduction, 10, 24, 30, 257, 289 Signs and Symptoms, 44, 176, 285, 289 Sil, 46, 289 Sinusitis, 14, 21, 32, 41, 47, 58, 72, 145, 150, 160, 172, 173, 176, 177, 289 Skeletal, 219, 232, 289 Skeleton, 215, 259, 289 Skull, 237, 289, 294 Sleep apnea, 177, 184, 289 Small cell lung cancer, 161, 289 Small intestine, 240, 253, 258, 290, 296 Smooth muscle, 10, 24, 140, 163, 164, 219, 227, 235, 253, 285, 290, 292 Social Environment, 283, 290 Sodium, 49, 149, 266, 276, 284, 290, 292 Soft tissue, 140, 226, 289, 290 Soft Tissue Injuries, 140, 290 Solid tumor, 220, 290 Solvent, 224, 244, 249, 290 Somatic, 253, 264, 266, 275, 290, 298 Spastic, 98, 105, 110, 259, 290 Spasticity, 290 Specialist, 205, 239, 290 Specificity, 41, 45, 216, 222, 242, 260, 288, 290 Spectrum, 25, 93, 180, 247, 290 Sperm, 219, 232, 278, 290 Sphenoid, 273, 288, 290 Sphincter, 260, 290 Spinal cord, 223, 230, 231, 232, 240, 264, 269, 270, 273, 275, 284, 291 Spinal Nerves, 275, 291 Spinous, 243, 259, 291 Spirometry, 13, 44, 200, 291 Spleen, 148, 237, 260, 262, 287, 291 Splenic Vein, 279, 291 Sporadic, 286, 291 Sputum, 17, 44, 64, 73, 78, 79, 98, 145, 157, 166, 167, 203, 291 Stabilization, 12, 291 Statistically significant, 5, 291 Steel, 232, 291 Stem cell transplantation, 87, 291 Stem Cells, 15, 217, 250, 291
Steroids, 47, 79, 236, 249, 291 Stimulant, 253, 259, 291 Stimulus, 227, 235, 257, 258, 260, 276, 284, 291, 294 Stomach, 26, 177, 215, 239, 244, 247, 248, 253, 258, 260, 262, 269, 275, 276, 284, 290, 291 Stool, 256, 259, 260, 291 Strand, 278, 291 Streptococcal, 176, 291 Streptococcus, 291 Stress, 37, 52, 53, 56, 149, 223, 248, 259, 269, 272, 280, 286, 292, 298 Stroke, 6, 21, 127, 139, 161, 163, 164, 169, 194, 229, 292 Stromal, 39, 242, 292 Stromal Cells, 39, 292 Subacute, 256, 289, 292 Subarachnoid, 251, 292 Subclinical, 256, 292 Subcutaneous, 180, 241, 247, 273, 292 Submaxillary, 243, 292 Subspecies, 290, 292 Substance P, 11, 159, 244, 265, 284, 287, 292 Substrate, 35, 139, 149, 163, 164, 243, 269, 292 Sudden death, 162, 292 Sulfur, 9, 23, 73, 99, 245, 265, 292 Sulfur Dioxide, 23, 73, 99, 292 Superoxide, 56, 292 Supplementation, 109, 292 Supportive care, 196, 292 Suppression, 8, 27, 236, 292 Surfactant, 155, 292 Surgical Wound Infection, 176, 292 Sweat, 49, 175, 292, 293 Sweat Glands, 49, 292, 293 Symphysis, 281, 293 Symptomatic, 22, 134, 144, 147, 227, 293 Symptomatic treatment, 144, 293 Synaptic, 270, 289, 293 Synaptic Transmission, 270, 293 Syncope, 72, 293 Systemic disease, 14, 254, 288, 293 Systemic lupus erythematosus, 81, 293 Systolic, 254, 293 T Tachycardia, 224, 293 Tachykinins, 160, 293 Tachypnea, 224, 293 Tacrolimus, 165, 293
Index 317
Tandem Repeat Sequences, 154, 293 Tear Gases, 259, 293 Temporal, 9, 45, 251, 293 Teratogenic, 259, 294 Terminator, 131, 294 Testosterone, 284, 294 Tetracycline, 25, 39, 294 Therapeutics, 25, 63, 64, 65, 66, 71, 74, 82, 84, 90, 105, 110, 190, 294 Thermal, 240, 270, 279, 294 Thermoregulation, 110, 294 Thoracic, 52, 82, 88, 99, 107, 108, 224, 239, 294 Threonine, 153, 274, 288, 294 Threshold, 254, 294 Thrombin, 135, 246, 278, 281, 294 Thrombocytes, 278, 294 Thrombolytic, 278, 294 Thrombomodulin, 281, 294 Thrombosis, 56, 224, 257, 258, 281, 292, 294 Thrombus, 56, 161, 162, 236, 256, 268, 278, 294 Thymidine, 133, 294 Thymidine Kinase, 133, 294 Thymus, 120, 255, 262, 294 Thyroid, 294, 297 Thyroxine, 217, 276, 288, 294 Tinnitus, 272, 294 Tissue Culture, 35, 57, 295 Tissue Plasminogen Activator, 94, 166, 295 Tolerance, 149, 215, 249, 295 Tomography, 61, 63, 109, 226, 295 Tonic, 10, 229, 295 Tooth Preparation, 215, 295 Toothache, 140, 295 Topical, 58, 100, 223, 244, 253, 259, 273, 295, 300 Toxaemia, 280, 295 Toxic, iv, 26, 53, 156, 162, 165, 223, 224, 238, 243, 245, 254, 270, 292, 295 Toxicity, 8, 9, 27, 34, 35, 43, 165, 240, 295 Toxicokinetics, 295 Toxicology, 23, 65, 73, 98, 196, 295 Toxins, 221, 249, 256, 266, 288, 295 Toxoplasmosis, 223, 295 Trace element, 232, 233, 295 Trachea, 154, 227, 245, 260, 276, 294, 296 Traction, 232, 296 Tractus, 10, 296 Transcription Factors, 15, 29, 296
Transduction, 10, 289, 296 Transfection, 225, 296 Transfer Factor, 255, 296 Transferases, 250, 296 Transient Ischemic Attacks, 162, 296 Translation, 47, 244, 296 Translocate, 34, 296 Translocation, 14, 233, 244, 296 Transmitter, 215, 223, 245, 258, 264, 271, 296 Transplantation, 8, 18, 20, 39, 56, 165, 255, 263, 296 Trauma, 244, 269, 296 Triad, 135, 296 Trypsin, 135, 156, 218, 232, 243, 296 Tuberculosis, 136, 153, 175, 176, 203, 235, 262, 267, 268, 296 Tumor marker, 218, 225, 296 Tumor Necrosis Factor, 136, 162, 296 Tumour, 136, 297 Tunica Intima, 242, 297 Tyrosine, 10, 12, 42, 229, 297 U Ulcerative colitis, 16, 93, 136, 160, 256, 297 Unconscious, 238, 254, 297 Uracil, 297 Urea, 292, 297 Uremia, 285, 297 Ureters, 260, 297 Urethra, 274, 281, 297 Uric, 164, 283, 297 Uricosuric, 280, 297 Uridine Triphosphate, 137, 297 Urinary, 5, 16, 61, 109, 224, 230, 232, 237, 248, 256, 282, 295, 297 Urinary Plasminogen Activator, 295, 297 Urinary tract, 5, 16, 61, 109, 224, 230, 282, 297 Urinary tract infection, 5, 61, 109, 224, 282, 297 Urine, 170, 224, 226, 237, 243, 256, 259, 281, 297 Urogenital, 151, 248, 250, 297 Urokinase, 166, 278, 297 Urticaria, 130, 219, 298 Uterus, 140, 164, 231, 236, 242, 264, 298 Uveitis, 222, 298 V Vaccination, 70, 77, 99, 131, 147, 151, 152, 298 Vaccine, 14, 21, 131, 132, 142, 147, 188, 216, 281, 298
318 Bronchitis
Vacuoles, 242, 272, 298 Vagal, 10, 298 Vagina, 140, 164, 231, 239, 264, 298, 299 Vaginal, 140, 164, 262, 298, 299 Vagus Nerve, 298 Vascular endothelial growth factor, 12, 298 Vasculitis, 44, 298 Vasoactive, 50, 139, 144, 163, 164, 298 Vasodilation, 140, 164, 298 Vasodilator, 227, 253, 268, 298 VE, 76, 162, 298 Vector, 131, 132, 296, 298 Vein, 220, 222, 258, 271, 273, 279, 287, 291, 298 Venous, 140, 151, 164, 222, 224, 231, 281, 298 Venous blood, 151, 231, 298 Ventilation, 23, 298 Ventilator, 89, 263, 285, 298 Venules, 12, 226, 228, 242, 265, 299 Vertigo, 218, 272, 299 Vesicular, 252, 299 Veterinary Medicine, 100, 101, 195, 299 Vibrio, 232, 299 Vibrio cholerae, 232, 299 Viral, 27, 33, 47, 58, 59, 133, 137, 165, 203, 215, 228, 236, 249, 256, 271, 283, 296, 299 Virion, 271, 299 Virulence, 21, 223, 295, 299 Virulent, 152, 299 Viscera, 290, 299
Viscosity, 42, 215, 226, 286, 299 Vitamin A, 138, 157, 257, 286, 299 Vitro, 9, 11, 14, 18, 23, 28, 29, 30, 32, 35, 37, 39, 43, 46, 53, 54, 59, 60, 61, 146, 149, 218, 226, 252, 255, 256, 278, 293, 295, 299 Vivo, 10, 11, 15, 27, 28, 29, 30, 33, 35, 39, 40, 42, 46, 52, 53, 54, 56, 60, 62, 131, 147, 149, 217, 252, 255, 256, 265, 267, 293, 299 Vulgaris, 115, 120, 299 Vulva, 299 Vulvovaginitis, 176, 299 W War, 76, 267, 299 Wart, 259, 299 Weight Gain, 246, 299 Wheezing, 26, 58, 109, 214, 299 White blood cell, 161, 221, 260, 262, 263, 266, 267, 270, 277, 300 Womb, 298, 300 Wound Healing, 148, 185, 257, 263, 300 X Xenograft, 220, 300 X-ray, 23, 71, 141, 203, 214, 226, 247, 258, 263, 271, 283, 300 X-ray therapy, 259, 300 Y Yeasts, 247, 276, 300 Z Zinc Oxide, 34, 300 Zoonoses, 283, 300 Zymogen, 232, 281, 300
Index 319
320 Bronchitis
