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

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Whooping Cough: 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: 0-597-84244-2 1. Whooping Cough-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on whooping cough. 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 WHOOPING COUGH ................................................................................. 3 Overview........................................................................................................................................ 3 Federally Funded Research on Whooping Cough .......................................................................... 3 E-Journals: PubMed Central ......................................................................................................... 9 The National Library of Medicine: PubMed ................................................................................ 22 CHAPTER 2. NUTRITION AND WHOOPING COUGH ....................................................................... 59 Overview...................................................................................................................................... 59 Finding Nutrition Studies on Whooping Cough ......................................................................... 59 Federal Resources on Nutrition ................................................................................................... 62 Additional Web Resources ........................................................................................................... 62 CHAPTER 3. ALTERNATIVE MEDICINE AND WHOOPING COUGH ................................................. 65 Overview...................................................................................................................................... 65 National Center for Complementary and Alternative Medicine.................................................. 65 Additional Web Resources ........................................................................................................... 68 General References ....................................................................................................................... 71 CHAPTER 4. DISSERTATIONS ON WHOOPING COUGH ................................................................... 73 Overview...................................................................................................................................... 73 Dissertations on Whooping Cough .............................................................................................. 73 Keeping Current .......................................................................................................................... 73 CHAPTER 5. PATENTS ON WHOOPING COUGH .............................................................................. 75 Overview...................................................................................................................................... 75 Patents on Whooping Cough ....................................................................................................... 75 Patent Applications on Whooping Cough.................................................................................... 95 Keeping Current ........................................................................................................................ 102 CHAPTER 6. BOOKS ON WHOOPING COUGH ............................................................................... 105 Overview.................................................................................................................................... 105 Book Summaries: Online Booksellers......................................................................................... 105 The National Library of Medicine Book Index ........................................................................... 106 Chapters on Whooping Cough ................................................................................................... 107 CHAPTER 7. MULTIMEDIA ON WHOOPING COUGH ..................................................................... 109 Overview.................................................................................................................................... 109 Bibliography: Multimedia on Whooping Cough ........................................................................ 109 CHAPTER 8. PERIODICALS AND NEWS ON WHOOPING COUGH .................................................. 111 Overview.................................................................................................................................... 111 News Services and Press Releases.............................................................................................. 111 Academic Periodicals covering Whooping Cough...................................................................... 115 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 117 Overview.................................................................................................................................... 117 U.S. Pharmacopeia..................................................................................................................... 117 Commercial Databases ............................................................................................................... 118 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 121 Overview.................................................................................................................................... 121 NIH Guidelines.......................................................................................................................... 121 NIH Databases........................................................................................................................... 123 Other Commercial Databases..................................................................................................... 125 APPENDIX B. PATIENT RESOURCES ............................................................................................... 127 Overview.................................................................................................................................... 127 Patient Guideline Sources.......................................................................................................... 127 Finding Associations.................................................................................................................. 131 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 133

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Overview.................................................................................................................................... 133 Preparation................................................................................................................................. 133 Finding a Local Medical Library................................................................................................ 133 Medical Libraries in the U.S. and Canada ................................................................................. 133 ONLINE GLOSSARIES................................................................................................................ 139 Online Dictionary Directories ................................................................................................... 141 WHOOPING COUGH DICTIONARY ...................................................................................... 143 INDEX .............................................................................................................................................. 179

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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 whooping cough 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 whooping cough, 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 whooping cough, 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 whooping cough. 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 whooping cough, 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 whooping cough. 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 WHOOPING COUGH Overview In this chapter, we will show you how to locate peer-reviewed references and studies on whooping cough.

Federally Funded Research on Whooping Cough The U.S. Government supports a variety of research studies relating to whooping cough. 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 whooping cough. 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 whooping cough. The following is typical of the type of information found when searching the CRISP database for whooping cough: •

Project Title: RECEPTORS

BORDETELLA

PERTUSSIS

AND

MONOCYTE

INTEGRIN

Principal Investigator & Institution: Relman, David A.; Assistant Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-MAR-1997; Project End 28-FEB-2002

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

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Summary: B. pertussis, the causative agent of whooping cough, is estimated to cause 600,000 deaths annually on a worldwide basis. Adherence and intoxication are the key elements of the interactions between B. pertussis and the human host. Filamentous hemagglutinin (FHA) is the dominant adhesin for this organism and a component of most acellular pertussis vaccines. It mediates attachment to a variety of host cells, including monocytes and macrophages. Recognition of FHA by leukocytes involves at least two integrin receptors: the complement 3 receptor (CR3) and the leukocyte response integrin (LRI). Recent data indicate that FHA induces signaling events in monocytes through LRI that enhance FHA recognition by CR3, and that FHA is necessary for B. pertussis inhibition of monocyte-dependent T- cell proliferative responses to antigen. Thus, the interactions between FHA and leukocyte integrins are proposed to be significant for two reasons: 1) FHA-mediated attachment of B. pertussis to monocytes may facilitate bacterial colonization, as well as modify host cellular immune responses; and 2) FHA can be used to study the binding and signaling capabilities of leukocyte integrins. The broad, long-term objectives of this application are to understand the mechanisms and implications of bacterial-integrin interactions. The more immediate goals of this proposal are to characterize FHA as a ligand for CR3 and LRI, to examine signaling molecules associated with FHA receptor ligation, and to examine the consequences of these interactions for B. pertussis pathogenesis. The specific aims of this proposal are: 1) To map the FHA domain(s) recognized by the complement receptor CR3. 2) To characterize signaling mechanisms associated with FHA-induced upregulated CR3 binding activity. 3) To examine the effect of B. pertussis binding on the topological distribution of monocyte integrin receptors and associated signaling molecules. 4) To examine B. pertussis inhibition of antigen-dependent T- cell proliferation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHALLENGE IMMUNOLOGY

WITH

B

PERTUSSIS--PATHOGENESIS

&

Principal Investigator & Institution: Yeh, Sylvia H.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Bordetella pertussis is the etiology of whooping cough which remains a significant cause of morbidity, particularly in young children. Despite successful childhood vaccination programs, outbreaks still occur in schools, medical institutions, and in communities both nationally and worldwide. This disease is underdiagnosed and grossly underreported, but the CDC records approximately 6,000 to 8,000 cases of pertussis each year with the highest incidence of disease in young children, the age group in whom disease is most severe. Several studies suggest that adolescents and adults are the reservoir of infection and source of transmission to young infants. Since B. pertussis is a pathogen only to humans, interrupting infection and transmission between individuals by improved vaccination and treatment may improve disease control lead to disease eradication. The goal of this proposal is to develop a safe human challenge model for detailed study of B. pertussis infection in healthy adults to elucidate the important pathogenic, clinical, epidemiological and immunologic aspects of B. pertussis infection. To date, most of our understanding of B. pertussis pathogenesis have relied on animal models, which are inadequate for application to human disease. With a human model, we will be able to 1) study the pathogenesis of B. pertussis in humans and evaluate the initial host inflammatory and immune responses following challenge, 2) evaluate susceptibility, incubation period and early clinical

Studies

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manifestations of B. pertussis, 3) characterize and expand our understanding of immunologic determinants of susceptibility and protection, 4) define mechanisms for long- term immunity to B. pertussis and 4) evaluate vaccine efficacy for the prevention of B. pertussis infection. Such information has not and probably cannot be derived from laboratory animals or other clinical trials and are crucially important to devise immunization strategies for improved pertussis control. Human challenge models are invaluable in the study of enteric infections, malaria, influenza and other respiratory infections. These models have proven useful to study the sequence of infection and disease, vaccine efficacy, antibiotic efficacy, and immune mechanisms involved with disease pathogenesis and protection. We hope to greatly refine the understanding of B. pertussis and develop improved means for diagnosis and prevention of disease in all age groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COORDINATION CHEMISTRY OF MICROBIAL ION TRANSPORT Principal Investigator & Institution: Raymond, Kenneth N.; Professor; Chemistry; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 01-APR-1976; Project End 31-MAY-2004 Summary: Iron is essential - yet toxic both in deficiency and excess. Increasingly the medical literature show that iron plays a key role in areas of human health. The focus of this research project is the essential role iron plays in bacterial growth, and hence the role of iron in human disease caused by bacteria or fungi. The goals are to characterize the mechanisms of siderophore-mediated iron uptake and to understand the role of siderophores in bacterial disease. Previous progress in this on-going project have involved the characterization of several siderophores from human pathogens, the quantitative determination and explanation of the stability or ferric siderophore complexes, the preparation and in vivo use of siderophore analogs, the characterization of the role stereochemistry at the metal center plays in the siderophore recognition and transport process and other aspects of siderophore coordination chemistry. The focus of this proposal now turns in a more microbiological direction. We will study the role of amonabactin in the virulence of Aeromonas hydrophyla, a human pathogen. The ability of this sideophore to remove iron from transferrin will probed and the gene it encodes for an enzyme in the synthesis of amonabactin, amoA, will be isolated to determined the importance of amonabactin in Aeromonas pathogenicity. Recognition and transport of ferric amonabactin will be probed using both four natural siderophores and synthetic analogs. The amonabactin receptor protein will be characterized. The siderophore for the organism that causes whooping cough in humans will be investigated with regard to its kinetic ability to remove iron, and its role in iron uptake will be probed. The latter stages of iron uptake into E.coli. mediated by enterobactin will be probed and the enterobactin esterase will be isolated and characterized. Collaborative studies on siderophores will include their biogeochemistry, marine biochemistry and the characterization of new siderophores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HOST-PATHOGEN INTERACTIONS IN THE MAMMALIAN AIRWAY Principal Investigator & Institution: Diamond, Gill; Associate Professor; Biochem and Molecular Biology; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007

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Whooping Cough

Summary: (provided by applicant): Epithelial cells lining the mammalian trachea form a crucial site in the host defense against airborne microbial pathogens, releasing numerous antimicrobial factors. Deficiencies in these defenses may result in recurrent airway infections. One of these defense mechanisms is the inducible production of betadefensins, a class of homologous antibiotic peptides highly abundant in mammalian epithelial cells. The genes encoding beta-defensins are expressed at high levels in the respiratory epithelium, and are induced by bacterial products and inflammatory mediators. Preliminary and published data support the hypothesis that some pathogenic strains of bacteria can evade the innate immune system in the airway by inhibiting beta-defensin gene expression, which can in turn diminish the antimicrobial defense of the airway. The mechanisms by which the specific bacterial virulence factors allow evasion of the first lines of host defense to colonize the airway are not yet defined. Elucidation of these mechanisms will aid in the development of therapeutic strategies for airway infections. The long-range goal of our research is to better understand the dynamic host defense systems in the airway. In this proposal we focus on the interactions of the airway pathogen, Bordetella bronchiseptica with its target cells in the respiratory epithelium. B. bronchiseptica is associated with respiratory infections in animals, and is closely related to B. pertussis, the causative agent of whooping cough in humans. We hypothesize that airway epithelial cells respond to bacteria by recognition of molecular patterns by specific receptors, resulting in the activation of NF-kappaB and induction of beta-defensin gene expression in order to prevent colonization. Pathogenic strains of B. bronchiseptica can prevent the increased production of antimicrobial peptides by interfering with the upregulation of the antimicrobial peptide genes through a type III secretion factor which interferes with the innate immune response. To test these hypotheses, the following aims are proposed: 1. Define the interaction of B. bronchiseptica with airway epithelial cells and the resultant induction of an innate immune response. 2. Define the mechanism of inhibition of innate immune induction by virulent B. bronchiseptica. The objective of these studies is to define how the airway epithelium responds to this model pathogen by the initiation of a host defense response. The second aim will determine how the bacterium circumvents this response utilizing proteomics to identify the bacterial factor responsible for this action, as well as a comprehensive characterization of the interaction of this factor and the defense response. The information will serve as a foundation for the development of novel therapies designed to work in the respiratory tract. This would include strategies to modulate the endogenous antimicrobial peptide expression to prevent serious bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IRON ACQISITION IN BORDETELLA PERTUSSIS Principal Investigator & Institution: Armstrong, Sandra K.; Microbiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 01-AUG-1991; Project End 30-NOV-2008 Summary: (provided by applicant): Bordetella pertussis is the bacterial agent that colonizes the human respiratory epithelium to cause whooping cough. To obtain nutritional iron, B. pertussis produces the siderophore alcaligin and also expresses activities required for utilization of host heme compounds as well as certain non-native siderophores, including the potent siderophore enterobactin. These three iron-retrieval systems have distinct positive transcriptional regulators that respond to the cognate iron source for maximal expression of the genes required for its utilization. The ability of Bordetella cells to selectively express relevant scavenging systems for available iron

Studies

7

sources may be important for effective adaptation and multiplication in the host environment. These studies will evaluate the humoral immune response of infected hosts to Bordetella iron system receptors and assess the in vivo importance of each of the three iron uptake systems in animal models of infection. Mechanistic features of siderophore signaling and transcriptional activation will be delineated for the alcaligin siderophore system and the enterobactin siderophore utilization system. The importance of the ability to transcriptionally respond to the appropriate iron source in vivo will be evaluated using Bordetella mutants producing novel hybrid regulators with reversed inducer and target gene specificities. A cell surface signaling phenomenon uniquely involved in regulation of the Bordetella host heme-iron utilization system will be investigated, and interacting signaling and regulatory protein domains will be defined. Spatiotemporal analysis of in vivo expression of the three iron systems will determine which systems are operational in the animal host and assess whether the systems are differentially expressed in certain tissue sites or during distinct stages of infection. Because B. pertussis is an obligate human pathogen with no known environmental or nonhuman animal reservoirs, it represents an ideal model organism for analysis of the host-parasite relationship and the physical, chemical and innate biological conditions that impact on the growth of bacteria in a host environment. This project will provide a better understanding of Bordetella pertussis pathogenic mechanisms and the infection process, as well as host immune responses involved in clearance and protection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PERTUSSIS TOXIN TRAFFICKING AND PROCESSING IN CELLS Principal Investigator & Institution: Carbonetti, Nicholas H.; Associate Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by the applicant):The short-term goal of this project is to understand the trafficking and activation of pertussis toxin (PT) within mammalian cells. Bordetella pertussis colonizes the human respiratory tract and causes the disease pertussis (whooping cough). Several systemic symptoms accompany this disease, even though B. pertussis is not thought to invade beyond the respiratory tract. Instead these symptoms are thought to be due to the action of PT, an exotoxin produced by B. pertussis. PT is an ADP ribosyltransferase that modifies several heterotrimeric G proteins, causing a wide range of effects on signaling in mammalian cells. How PT is transported within mammalian cells to arrive at its target proteins in an active form is largely unknown. In addition, how PT is transported from the respiratory tract to systemic sites is completely unknown. Understanding the mechanisms utilized by this complex toxin to achieve these effects will provide key information on the cell biology of PT and will help to provide a groundwork for studies to elucidate the role of this toxin in B. pertussis infection and disease. In addition, this information may allow development of therapeutics to combat the effects of the toxin and may also allow improvement of existing pertussis vaccines that include PT or development of novel vaccine molecules using PT as a intracellular delivery vector. We have preliminary data indicating that (i) PT may undergo retrograde intracellular trafficking through the Golgi apparatus and endoplasmic reticulum (ER) en route to its cytosolic target proteins, (ii) that proteolytic processing of the active Si subunit of cell-associated PT occurs and may be important for its activity, and (iii) that there is apparent transcytosis of active PT across intact polarized epithelial cells in culture. Therefore the specific aims of this

8

Whooping Cough

proposal are to investigate the trafficking, processing and transcytosis of PT in mammalian cells and the key features of this toxin that mediate these events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEVENTH INTERNATIONAL SYMPOSIUM ON PERTUSSIS Principal Investigator & Institution: Hewlett, Erik L.; Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-SEP-2003 Summary: (provided by applicant): Whooping cough remains a significant health problem worldwide causing nearly half a million deaths a year. This disease has been controlled, but not eliminated, by vaccination in the U.S., but areas for vaccine improvement have been identified. The Seventh International Symposium on Pertussis: Genome, Pathogenesis and Immunity will be held 18th thru 22nd of September, 2002, in Cambridge England. Targeted participants include researchers in the field of pertussis with a special emphasis on basic mechanisms of Pathogenesis and immune responses to Bordetella pertussis but will be open to any interested party. Anticipated attendance is 200 to 300 scientists, clinicians, vaccine maufacturers, and public health and regulatory officials. The goals of the meeting are to present cutting-edge research and promote synthesis of new ideas. Topics to be covered include: Updated information on known and potential virulence factors (adhesions and toxins), Regulation of virulence factor expression, Information from the Bordetella genomes, Microarray analysis of host gene expression, Lessons from epidemiologic studies and clinical trials, Immunologic responses, and other investigations of pathogensis in humans. In the last session, we will attempt to develop a consolidated model of pertusis pathogenesis. To encourage participation we will use an interactive poster format. Posters with a diagrammatic outline of the problems under discussion will be available throughout the meeting for participants to write on, offering both insights or questions they hope will be addressed. Experts in the area will summarize the poster and draw overall conclusions. This meeting will lead to a greater scientific understanding of the biology of this organism, and the promise for developing a more effective means to control this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TYPE III SECRETION IN BORDETELLA PATHOGENESIS Principal Investigator & Institution: Yuk, Ming H.; Assistant Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The type III secretion system of Bordetella bronchiseptica is chosen as a model system for studying bacterial-host interactions at the molecular level. B. bronchiseptica is a specialized respiratory pathogen closely related to B. pertussis (which causes whooping cough in humans). However, B. bronchiseptica naturally infects many laboratory animals, which allow us to study bacterial-host interactions in the context of natural infections. We have discovered a type III secretion system in B. bronchiseptica. Type III secretion systems are found in several pathogenic Gram-negative bacteria and can deliver proteins directly into the host cytoplasm or plasma membrane upon contact of the bacteria with the host cell. We have identified 22 linked genes in the B. bronchiseptica genome encoding proteins for a type III secretion system. By comparing the in vitro phenotypes of the wild type bacteria with a bscN deletion strain (that is defective in type III secretion) in their interactions with cultured cell lines, we deduced that type III secreted factors have a variety of effects on host cells.

Studies

9

These include: induction of cytotoxicity, inhibition of activation of the transcription factor NF-kB by the aberrant aggregation of this factor in the cytoplasm, and activation of the ERK MAP kinase pathway. In vivo studies showed that type III secretion is required for persistent colonization in the trachea of rats and mice and the downmodulation of anti-Bordetella antibody production. Based on these observations, we hypothesize that type III secreted factors from B. bronchiseptica play immunomodulatory roles for the bacteria to attain persistent, chronic colonization. The objective of this study is to identify the specific effector proteins secreted by the type III secretion system in B. bronchiseptica and determine how they alter host cellular processes and immune responses. We shall identify type III secreted proteins from B. bronchiseptica by both biochemical and genomic approaches, and use in vitro infection models to determine the mechanisms by which the effector protein(s) inhibit NF-kB activation and activate the MAP kinase pathways. We shall also use the mouse infection model to determine the importance of down-regulation of humoral immunity in allowing persistent colonization of the bacteria and how type III secreted virulence proteins interact with host immune cell functions. By identifying the bacterial effector proteins and examining how they interact with host cells, we shall determine the molecular basis for pathogenesis and down-regulation of immune processes. 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 “whooping cough” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for whooping cough in the PubMed Central database: •

A Murine Model in Which Protection Correlates with Pertussis Vaccine Efficacy in Children Reveals Complementary Roles for Humoral and Cell-Mediated Immunity in Protection against Bordetella pertussis. by Mills KH, Ryan M, Ryan E, Mahon BP.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107945

•

A Regulatory Role for Interleukin 4 in Differential Inflammatory Responses in the Lung following Infection of Mice Primed with Th1- or Th2-Inducing Pertussis Vaccines. by McGuirk P, Mills KH.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97292

•

Acute Bordetella pertussis infection in an adult. by Smith S, Tilton RC.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228812

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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Adhesion of Bordetella pertussis to Eukaryotic Cells Requires a Time- Dependent Export and Maturation of Filamentous Hemagglutinin. by Arico B, Nuti S, Scarlato V, Rappuoli R.; 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47531

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Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres. by Shahin R, Leef M, Eldridge J, Hudson M, Gilley R.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173134

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Analysis of a repetitive DNA sequence from Bordetella pertussis and its application to the diagnosis of pertussis using the polymerase chain reaction. by Glare EM, Paton JC, Premier RR, Lawrence AJ, Nisbet IT.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268090

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Analysis of Bordetella pertussis isolates from an epidemic by pulsed-field gel electrophoresis. by Beall B, Cassiday PK, Sanden GN.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228648

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Analysis of BvgA Activation of the Pertactin Gene Promoter in Bordetella pertussis. by Kinnear SM, Boucher PE, Stibitz S, Carbonetti NH.; 1999 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94027

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Analysis with a Combination of Macrorestriction Endonucleases Reveals a High Degree of Polymorphism among Bordetella pertussis Isolates in Eastern France. by Prevost G, Freitas FI, Stoessel P, Meunier O, Haubensack M, Monteil H, Scheftel JM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88650

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Antibacterial Agents and Release of Periplasmic Pertussis Toxin from Bordetella pertussis. by Craig-Mylius KA, Weiss AA.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89879

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Antigenic Analysis of Bordetella pertussis Filamentous Hemagglutinin with Phage Display Libraries and Rabbit Anti-Filamentous Hemagglutinin Polyclonal Antibodies. by Wilson DR, Siebers A, Finlay BB.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108604

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Antimicrobial susceptibilities of Bordetella species isolated in a Multicenter Pertussis Surveillance Project. by Kurzynski TA, Boehm DM, Rott-Petri JA, Schell RF, Allison PE.; 1988 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172115

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Antimicrobial Susceptibility Testing of Clinical Isolates of Bordetella pertussis from Northern California: Report from the SENTRY Antimicrobial Surveillance Program. by Gordon KA, Fusco J, Biedenbach DJ, Pfaller MA, Jones RN.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90876

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Bordetella parapertussis Infection in Children: Epidemiology, Clinical Symptoms, and Molecular Characteristics of Isolates. by Mastrantonio P, Stefanelli P, Giuliano M, Rojas YH, Ciofi degli Atti M, Anemona A, Tozzi AE.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104677

Studies

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Bordetella pertussis Autoregulates Pertussis Toxin Production through the Metabolism of Cysteine. by Bogdan JA, Nazario-Larrieu J, Sarwar J, Alexander P, Blake MS.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100060

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Bordetella pertussis binds the human complement regulator C4BP: role of filamentous hemagglutinin. by Berggard K, Johnsson E, Mooi FR, Lindahl G.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175517

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Bordetella pertussis Isolates with a Heterogeneous Phenotype for Erythromycin Resistance. by Wilson KE, Cassiday PK, Popovic T, Sanden GN.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120648

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Bordetella pertussis TonB, a Bvg-Independent Virulence Determinant. by Pradel E, Guiso N, Menozzi FD, Locht C.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97367

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Bordetella pertussis Tracheal Cytotoxin and Other Muramyl Peptides: Distinct Structure-Activity Relationships for Respiratory Epithelial Cytopathology. by Luker KE, Collier JL, Kolodziej EW, Marshall GR, Goldman WE.; 1993 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46087

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Bordetella pertussis versus non-L. pneumophila Legionella spp.: a continuing diagnostic challenge. by Ng V, Weir L, York MK, Hadley WK.; 1992 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270658

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Bordetella pertussis Virulence Factors Affect Phagocytosis by Human Neutrophils. by Weingart CL, Weiss AA.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97341

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Cell-Mediated Immune Responses in Four-Year-Old Children after Primary Immunization with Acellular Pertussis Vaccines. by Ausiello CM, Lande R, Urbani F, la Sala A, Stefanelli P, Salmaso S, Mastrantonio P, Cassone A.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96703

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Characterization of antibody inhibiting adherence of Bordetella pertussis to human respiratory epithelial cells. by Tuomanen EI, Zapiain LA, Galvan P, Hewlett EL.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271278

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Characterization of Human Bactericidal Antibodies to Bordetella pertussis. by Weiss AA, Mobberley PS, Fernandez RC, Mink CM.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96476

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Characterization of the bvgR Locus of Bordetella pertussis. by Merkel TJ, Barros C, Stibitz S.; 1998 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107078

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Comparison of blood-free medium (cyclodextrin solid medium) with Bordet-Gengou medium for clinical isolation of Bordetella pertussis. by Aoyama T, Murase Y, Iwata T, Imaizumi A, Suzuki Y, Sato Y.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268790

12

Whooping Cough

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Comparison of Five Commercial Enzyme-Linked Immunosorbent Assays for Detection of Antibodies to Bordetella pertussis. by Kosters K, Riffelmann M, Dohrn B, von Konig CH.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95889

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Comparison of modified Bordet-Gengou and modified Regan-Lowe media for the isolation of Bordetella pertussis and Bordetella parapertussis. by Kurzynski TA, Boehm DM, Rott-Petri JA, Schell RF, Allison PE.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266968

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Comparison of nasopharyngeal aspirates with swabs for culture of Bordetella pertussis. by Hallander HO, Reizenstein E, Renemar B, Rasmuson G, Mardin L, Olin P.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262619

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Comparison of PCR, Culture, and Direct Fluorescent-Antibody Testing for Detection of Bordetella pertussis. by Loeffelholz MJ, Thompson CJ, Long KS, Gilchrist MJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85400

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Comparison of polymerase chain reaction with culture and enzyme immunoassay for diagnosis of pertussis. by He Q, Mertsola J, Soini H, Skurnik M, Ruuskanen O, Viljanen MK.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262834

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Comparison of polymerase chain reaction, culture, and western immunoblot serology for diagnosis of Bordetella pertussis infection. by Grimprel E, Begue P, Anjak I, Betsou F, Guiso N.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266003

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Comparison of throat and nasopharyngeal swab specimens for culture diagnosis of Bordetella pertussis infection. by Marcon MJ, Hamoudi AC, Cannon HJ, Hribar MM.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269146

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Construction of Bordetella pertussis strains that overproduce genetically inactivated pertussis toxin. by Zealey GR, Loosmore SM, Yacoob RK, Cockle SA, Herbert AB, Miller LD, Mackay NJ, Klein MH.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195193

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Contribution of Regulation by the bvg Locus to Respiratory Infection of Mice by Bordetella pertussis. by Merkel TJ, Stibitz S, Keith JM, Leef M, Shahin R.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108527

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Cytokine mRNA Expression and Proliferative Responses Induced by Pertussis Toxin, Filamentous Hemagglutinin, and Pertactin of Bordetella pertussis in the Peripheral Blood Mononuclear Cells of Infected and Immunized Schoolchildren and Adults. by He Q, Minh NN, Edelman K, Viljanen MK, Arvilommi H, Mertsola J.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108420

Studies

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Delayed immunisation and risk of pertussis in infants: unmatched case-control study. by Grant CC, Roberts M, Scragg R, Stewart J, Lennon D, Kivell D, Ford R, Menzies R.; 2003 Apr 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153471

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Delivery of Multiple Epitopes by Recombinant Detoxified Adenylate Cyclase of Bordetella pertussis Induces Protective Antiviral Immunity. by Fayolle C, Osickova A, Osicka R, Henry T, Rojas MJ, Saron MF, Sebo P, Leclerc C.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114968

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Detection of Bordetella pertussis by rapid-cycle PCR and colorimetric microwell hybridization. by Buck GE.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229024

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Detection of Bordetella pertussis in clinical specimens by PCR and a microtiter platebased DNA hybridization assay. by Nelson S, Matlow A, McDowell C, Roscoe M, Karmali M, Penn L, Dyster L.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229522

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Development of a rapid diagnostic test for pertussis: direct detection of pertussis toxin in respiratory secretions. by Friedman RL, Paulaitis S, McMillan JW.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267059

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Diagnosis of Community-Acquired Pertussis Infection: Comparison of Both Culture and Fluorescent-Antibody Assays with PCR Detection Using Electrophoresis or Dot Blot Hybridization. by Lingappa JR, Lawrence W, West-Keefe S, Gautom R, Cookson BT.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120624

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Differences in coughing and other responses to intrabronchial infection with Bordetella pertussis among strains of rats. by Hall E, Parton R, Wardlaw AC.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175676

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Differential Regulation of Bvg-Activated Virulence Factors Plays a Role in Bordetella pertussis Pathogenicity. by Kinnear SM, Marques RR, Carbonetti NH.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98121

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Efficacy of enzyme-linked immunosorbent assay for rapid diagnosis of Bordetella pertussis infection. by Lawrence AJ, Paton JC.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269420

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Eighty-Kilodalton N-Terminal Moiety of Bordetella pertussis Filamentous Hemagglutinin: Adherence, Immunogenicity, and Protective Role. by Alonso S, Reveneau N, Pethe K, Locht C.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128203

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Enzyme-linked immunosorbent assay for detection of pertussis immunoglobulin A in nasopharyngeal secretions as an indicator of recent infection. by Goodman YE, Wort AJ, Jackson FL.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=273779

14

Whooping Cough

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Epithelial Autotoxicity of Nitric Oxide: Role in the Respiratory Cytopathology of Pertussis. by Heiss LN, Lancaster JR Jr, Corbett JA, Goldman WE.; 1994 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42928

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Evaluation and validation of a monoclonal immunofluorescent reagent for direct detection of Bordetella pertussis. by McNicol P, Giercke SM, Gray M, Martin D, Brodeur B, Peppler MS, Williams T, Hammond G.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228597

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Evaluation of an Immunoglobulin G Enzyme-Linked Immunosorbent Assay for Pertussis Toxin and Filamentous Hemagglutinin in Diagnosis of Pertussis in Senegal. by Simondon F, Iteman I, Preziosi MP, Yam A, Guiso N.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121348

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Evaluation of culture, immunofluorescence, and serology for the diagnosis of pertussis. by Halperin SA, Bortolussi R, Wort AJ.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267411

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Evaluation of PCR for Diagnosis of Bordetella pertussis and Bordetella parapertussis Infections. by Lind-Brandberg L, Welinder-Olsson C, Lagergard T, Taranger J, Trollfors B, Zackrisson G.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104608

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Evaluation of serologic assays for diagnosis of whooping cough. by Granstrom G, Wretlind B, Salenstedt CR, Granstrom M.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266723

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Genital Antibody Responses in Mice after Intranasal Infection with an Attenuated Candidate Vector Strain of Bordetella pertussis. by Mielcarek N, Nordstrom I, Menozzi FD, Locht C, Holmgren J.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97167

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Genomic Plasticity in Natural Populations of Bordetella pertussis. by Stibitz S, Yang MS.; 1999 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94064

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Genotypic Variation in the Bordetella pertussis Virulence Factors Pertactin and Pertussis Toxin in Historical and Recent Clinical Isolates in the United Kingdom. by Fry NK, Neal S, Harrison TG, Miller E, Matthews R, George RC.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98665

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Humoral and Cellular Immune Responses in Mice Immunized with Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Producing a Pertussis Toxin-Tetanus Toxin Hybrid Protein. by Abomoelak B, Huygen K, Kremer L, Turneer M, Locht C.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96858

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Identification and Characterization of Heparin Binding Regions of the Fim2 Subunit of Bordetella pertussis. by Geuijen CA, Willems RJ, Hoogerhout P, Puijk WC, Meloen RH, Mooi FR.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108189

Studies

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Identification and Cloning of waaF (rfaF) from Bordetella pertussis and Use To Generate Mutants of Bordetella spp. with Deep Rough Lipopolysaccharide. by Allen AG, Isobe T, Maskell DJ.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106845

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Identification of AlcR, an AraC-Type Regulator of Alcaligin Siderophore Synthesis in Bordetella bronchiseptica and Bordetella pertussis. by Pradel E, Guiso N, Locht C.; 1998 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106966

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Identification of Bordetella pertussis infection by shared-primer PCR. by Li Z, Jansen DL, Finn TM, Halperin SA, Kasina A, O'Connor SP, Aoyama T, Manclark CR, Brennan MJ.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263124

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Identification of two bvg-repressed surface proteins of Bordetella pertussis. by Stenson TH, Peppler MS.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173531

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Immunoblot analysis of humoral immune responses following infection with Bordetella pertussis or immunization with diphtheria-tetanus-pertussis vaccine. by Redd SC, Rumschlag HS, Biellik RJ, Sanden GN, Reimer CB, Cohen ML.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266612

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Immunogenicity and Protective Efficacy of Neonatal Vaccination against Bordetella pertussis in a Murine Model: Evidence for Early Control of Pertussis. by Roduit C, Bozzotti P, Mielcarek N, Lambert PH, del Giudice G, Locht C, Siegrist CA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128115

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Immunoglobulin A antibodies to pertussis toxin and filamentous hemagglutinin in saliva from patients with pertussis. by Zackrisson G, Lagergard T, Trollfors B, Krantz I.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267977

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Immunoglobulin A-Mediated Protection against Bordetella pertussis Infection. by Hellwig SM, van Spriel AB, Schellekens JF, Mooi FR, van de Winkel JG.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98573

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Immunomagnetic separation and solid-phase detection of Bordetella pertussis. by Stark M, Reizenstein E, Uhlen M, Lundeberg J.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228892

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Impact of Nasopharyngeal Swab Types on Detection of Bordetella pertussis by PCR and Culture. by Cloud JL, Hymas W, Carroll KC.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130882

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Importance of culture in laboratory diagnosis of Bordetella pertussis infections. by Gilligan PH, Fisher MC.; 1984 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271468

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Whooping Cough

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In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to four fluoroquinolones (levofloxacin, d-ofloxacin, ofloxacin, and ciprofloxacin), cefpirome, and meropenem. by Hoppe JE, Rahimi-Galougahi E, Seibert G.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163206

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In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to seven fluoroquinolones. by Hoppe JE, Simon CG.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172042

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In vitro susceptibility of Bordetella parapertussis to various antimicrobial agents. by Watanabe M, Haraguchi Y.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284266

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Inhibition of PCR-based assay for Bordetella pertussis by using calcium alginate fiber and aluminum shaft components of a nasopharyngeal swab. by Wadowsky RM, Laus S, Libert T, States SJ, Ehrlich GD.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267180

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Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells. by Mahon BP, Ryan MS, Griffin F, Mills KH.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174522

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Intracellular Delivery of a Cytolytic T-Lymphocyte Epitope Peptide by Pertussis Toxin to Major Histocompatibility Complex Class I without Involvement of the Cytosolic Class I Antigen Processing Pathway. by Carbonetti NH, Irish TJ, Chen CH, O'Connell CB, Hadley GA, McNamara U, Tuskan RG, Lewis GK.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96361

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Investigation of Role of Nitric Oxide in Protection from Bordetella pertussis Respiratory Challenge. by Canthaboo C, Xing D, Wei XQ, Corbel MJ.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127720

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IS481 and IS1002 of Bordetella pertussis Create a 6-Base-Pair Duplication upon Insertion at a Consensus Target Site. by Stibitz S.; 1998 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107526

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Issues Associated with and Recommendations for Using PCR To Detect Outbreaks of Pertussis. by Lievano FA, Reynolds MA, Waring AL, Ackelsberg J, Bisgard KM, Sanden GN, Guris D, Golaz A, Bopp DJ, Limberger RJ, Smith PF.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120629

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Laboratory diagnosis of pertussis: state of the art in 1997. by Muller FM, Hoppe JE, Wirsing von Konig CH.; 1997 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=229988

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Long-term human serum antibody responses after immunization with whole-cell pertussis vaccine in France. by Grimprel E, Begue P, Anjak I, Njamkepo E, Francois P, Guiso N.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170254

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Long-Term Pertussis-Specific Immunity after Primary Vaccination with a Combined Diphtheria, Tetanus, Tricomponent Acellular Pertussis, and Hepatitis B Vaccine in Comparison with That after Natural Infection. by Esposito S, Agliardi T, Giammanco A, Faldella G, Cascio A, Bosis S, Friscia O, Clerici M, Principi N.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98527

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Major outbreak of pertussis in northern Alberta, Canada: analysis of discrepant direct fluorescent-antibody and culture results by using polymerase chain reaction methodology. by Ewanowich CA, Chui LW, Paranchych MG, Peppler MS, Marusyk RG, Albritton WL.; 1993 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265620

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Mucosal Immunization with a Genetically Engineered Pertussis Toxin S1 FragmentCholera Toxin Subunit B Chimeric Protein. by Lee SF, Halperin SA, Salloum DF, MacMillan A, Morris A.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152103

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Multilocus Sequence Typing of Bordetella pertussis Based on Surface Protein Genes. by van Loo IH, Heuvelman KJ, King AJ, Mooi FR.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130760

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Multiplex LightCycler PCR Assay for Detection and Differentiation of Bordetella pertussis and Bordetella parapertussis in Nasopharyngeal Specimens. by Sloan LM, Hopkins MK, Mitchell PS, Vetter EA, Rosenblatt JE, Harmsen WS, Cockerill FR, Patel R.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120124

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Multiplex PCR-based assay for detection of Bordetella pertussis in nasopharyngeal swab specimens. by Wadowsky RM, Michaels RH, Libert T, Kingsley LA, Ehrlich GD.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229378

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Mutants of Escherichia coli Heat-Labile Toxin Act as Effective Mucosal Adjuvants for Nasal Delivery of an Acellular Pertussis Vaccine: Differential Effects of the Nontoxic AB Complex and Enzyme Activity on Th1 and Th2 Cells. by Ryan EJ, McNeela E, Murphy GA, Stewart H, O'hagan D, Pizza M, Rappuoli R, Mills KH.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97029

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Mutations Affecting the [alpha] Subunit of Bordetella pertussis RNA Polymerase Suppress Growth Inhibition Conferred by Short C-Terminal Deletions of the Response Regulator BvgA. by Stibitz S.; 1998 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107192

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Mutations in the S1 Subunit of Pertussis Toxin That Affect Secretion. by Craig-Mylius KA, Stenson TH, Weiss AA.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97279

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Neither the Bvg[minus sign] Phase nor the vrg6 Locus of Bordetella pertussis Is Required for Respiratory Infection in Mice. by Martinez de Tejada G, Cotter PA, Heininger U, Camilli A, Akerley BJ, Mekalanos JJ, Miller JF.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108267

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Nested Duplex PCR To Detect Bordetella pertussis and Bordetella parapertussis and Its Application in Diagnosis of Pertussis in Nonmetropolitan Southeast Queensland, Australia. by Farrell DJ, Daggard G, Mukkur TK.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84487

18

Whooping Cough

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Orally administered microencapsulated Bordetella pertussis fimbriae protect mice from B. pertussis respiratory infection. by Jones DH, McBride BW, Thornton C, O'Hagan DT, Robinson A, Farrar GH.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173791

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Pertussis control in Canada. by Halperin SA.; 2003 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155940

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Pertussis immunisation. by Berger A.; 2003 Apr 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153472

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Pertussis in adults. by Hoey J.; 2003 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143554

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Pertussis outbreak in Austin and Travis County, Texas, 1975. by Field LH, Parker CD.; 1977 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=274724

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Polymorphism in the Pertussis Toxin Promoter Region Affecting the DNA-Based Diagnosis of Bordetella Infection. by Nygren M, Reizenstein E, Ronaghi M, Lundeberg J.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86018

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Polymorphism of Bordetella pertussis Isolates Circulating for the Last 10 Years in France, Where a Single Effective Whole-Cell Vaccine Has Been Used for More than 30 Years. by Weber C, Boursaux-Eude C, Coralie G, Caro V, Guiso N.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88555

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Pregenomic Comparative Analysis between Bordetella bronchiseptica RB50 and Bordetella pertussis Tohama I in Murine Models of Respiratory Tract Infection. by Harvill ET, Cotter PA, Miller JF.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97000

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Preparation of filamentous hemagglutinin from Bordetella pertussis and assay for serum antibodies to filamentous hemagglutinin and pertussis toxin for clinical and public health laboratories. by Wong KH, Skelton SK.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267130

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Protective Effects of Pertussis Immunoglobulin (P-IGIV) in the Aerosol Challenge Model. by Bruss JB, Siber GR.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95709

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Protective Immunogenicity of Two Synthetic Peptides Selected From the Amino Acid Sequence of Bordetella pertussis Toxin Subunit S1. by Askelof P, Rodmalm K, Wrangsell G, Larsson U, Svenson SB, Cowell JL, Unden A, Bartfai T.; 1990 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53472

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Quantitative Priming with Inactivated Pertussis Toxoid Vaccine in the Aerosol Challenge Model. by Bruss JB, Siber GR.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128194

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Rapid detection of Bordetella pertussis by a monoclonal antibody-based colony blot assay. by Gustafsson B, Askelof P.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267385

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Rapid diagnosis of pertussis in young infants: comparison of culture, PCR, and infant's and mother's serology. by Grimprel E, Njamkepo E, Begue P, Guiso N.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170648

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Rapid-Cycle PCR Method To Detect Bordetella pertussis That Fulfills All Consensus Recommendations for Use of PCR in Diagnosis of Pertussis. by Farrell DJ, McKeon M, Daggard G, Loeffelholz MJ, Thompson CJ, Mukkur TK.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87627

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Real-Time LightCycler PCR for Detection and Discrimination of Bordetella pertussis and Bordetella parapertussis. by Kosters K, Reischl U, Schmetz J, Riffelmann M, Wirsing von Konig CH.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130942

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Reciprocal Protective Immunity against Bordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection. by Watanabe M, Nagai M.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100078

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Recombinant Mycobacterium bovis BCG Expressing Pertussis Toxin Subunit S1 Induces Protection against an Intracerebral Challenge with Live Bordetella pertussis in Mice. by Nascimento IP, Dias WO, Mazzantini RP, Miyaji EN, Gamberini M, Quintilio W, Gebara VC, Cardoso DF, Ho PL, Raw I, Winter N, Gicquel B, Rappuoli R, Leite LC.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101688

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Recovery of Bordetella holmesii from Patients with Pertussis-Like Symptoms: Use of Pulsed-Field Gel Electrophoresis To Characterize Circulating Strains. by Mazengia E, Silva EA, Peppe JA, Timperi R, George H.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86794

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Role of Adenylate Cyclase-Hemolysin in Alveolar Macrophage Apoptosis during Bordetella pertussis Infection In Vivo. by Gueirard P, Druilhe A, Pretolani M, Guiso N.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108109

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Role of Adhesins and Toxins in Invasion of Human Tracheal Epithelial Cells by Bordetella pertussis. by Bassinet L, Gueirard P, Maitre B, Housset B, Gounon P, Guiso N.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97369

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Role of ADP-Ribosyltransferase Activity of Pertussis Toxin in Toxin-Adhesin Redundancy with Filamentous Hemagglutinin during Bordetella pertussis Infection. by Alonso S, Pethe K, Mielcarek N, Raze D, Locht C.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98732

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Role of Antibodies against Bordetella pertussis Virulence Factors in Adherence of Bordetella pertussis and Bordetella parapertussis to Human Bronchial Epithelial cells. by van den Berg BM, Beekhuizen H, Mooi FR, van Furth R.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96428

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Role of gamma interferon in natural clearance of Bordetella pertussis infection. by Barbic J, Leef MF, Burns DL, Shahin RD.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175707

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Role of Systemic and Mucosal Immune Responses in Reciprocal Protection against Bordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection. by Watanabe M, Nagai M.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145389

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Role of the Bordetella pertussis minor fimbrial subunit, FimD, in colonization of the mouse respiratory tract. by Geuijen CA, Willems RJ, Bongaerts M, Top J, Gielen H, Mooi FR.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175606

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Serum Immunoglobulin G Antibody Responses to Bordetella pertussis Lipooligosaccharide and B. parapertussis Lipopolysaccharide in Children with Pertussis and Parapertussis. by Trollfors B, Lagergard T, Taranger J, Bergfors E, Schneerson R, Robbins JB.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96188

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Simple, speedy, sensitive, and specific serodiagnosis of pertussis by using a particle agglutination test. by Aoyama T, Kato T, Takeuchi Y, Kato K, Morokuma K, Hirai T.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229857

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Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough. by Granstrom G, Askelof P, Granstrom M.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266476

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Specificity and Sensitivity of High Levels of Immunoglobulin G Antibodies against Pertussis Toxin in a Single Serum Sample for Diagnosis of Infection with Bordetella pertussis. by de Melker HE, Versteegh FG, Conyn-van Spaendonck MA, Elvers LH, Berbers GA, van der Zee A, Schellekens JF.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86208

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Speedy, Sensitive, and Specific Diagnosis of Pertussis by Using Serum and the Sensitized-Particle Test. by Arya SC.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124870

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Stable expression of pertussis toxin in Bordetella bronchiseptica under the control of a tightly regulated promoter. by Suarez A, Staendner LH, Rohde M, Piatti G, Timmis KN, Guzman CA.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168309

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Subclass compositions of immunoglobulin G to pertussis toxin in patients with whooping cough, in healthy individuals, and in recipients of a pertussis toxoid vaccine. by Zackrisson G, Lagergard T, Trollfors B.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267616

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Suppression of Platelet Aggregation by Bordetella pertussis Adenylate Cyclase Toxin. by Iwaki M, Kamachi K, Heveker N, Konda T.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96579

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Targeted Mutations that Ablate Either the Adenylate Cyclase or Hemolysin Function of the Bifunctional cyaA Toxin of Bordetella pertussis Abolish Virulence. by Gross MK, Au DC, Smith AL, Storm DR.; 1992 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49195

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The transcriptional responses of respiratory epithelial cells to Bordetella pertussis reveal host defensive and pathogen counter-defensive strategies. by Belcher CE, Drenkow J, Kehoe B, Gingeras TR, McNamara N, Lemjabbar H, Basbaum C, Relman DA.; 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17664

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Use of a Chinese hamster ovary cell cytotoxicity assay for the rapid diagnosis of pertussis. by Halperin SA, Bortolussi R, Kasina A, Wort AJ.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269532

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Use of Pertussis Toxin Encoded by ptx Genes from Bordetella bronchiseptica To Model the Effects of Antigenic Drift of Pertussis Toxin on Antibody Neutralization. by Hausman SZ, Burns DL.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97675

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Use of pulsed-field gel electrophoresis for epidemiological study of Bordetella pertussis in a whooping cough outbreak. by de Moissac YR, Ronald SL, Peppler MS.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263043

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Use of supplemented Stainer-Scholte broth for the isolation of Bordetella pertussis from clinical material. by von Koenig CH, Tacken A, Finger H.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266945

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Vaccination with Bordetella pertussis-Pulsed Autologous or Heterologous Dendritic Cells Induces a Mucosal Antibody Response In Vivo and Protects against Infection. by George-Chandy A, Mielcarek N, Nordstrom I, Holmgren J, Eriksson K.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98478

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Validation of nested Bordetella PCR in pertussis vaccine trial. by Reizenstein E, Lindberg L, Mollby R, Hallander HO.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228897

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Whole-Cell but Not Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-Induced Interleukin-1[beta] in a New Murine Model for Analysis of Neuronal Side Effects of Vaccination. by Donnelly S, Loscher CE, Lynch MA, Mills KH.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98454

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

A clinical validation of Bordetella pertussis and Bordetella parapertussis polymerase chain reaction: comparison with culture and serology using samples from patients with suspected whooping cough from a highly immunized population. Author(s): van der Zee A, Agterberg C, Peeters M, Mooi F, Schellekens J. Source: The Journal of Infectious Diseases. 1996 July; 174(1): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8656019&dopt=Abstract

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A model basis for the control of whooping cough. Author(s): Knox EG, Shannon HS. Source: International Journal of Epidemiology. 1986 December; 15(4): 544-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3818164&dopt=Abstract

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A new diagnostic method for whooping cough. Author(s): Peller P, Dickelhuber I. Source: Chemioterapia. 1987 June; 6(2 Suppl): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2908242&dopt=Abstract

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A search for subclinical infection during a small outbreak of whooping cough: implications for clinical diagnosis. Author(s): Jenkinson D, Pepper JD. Source: J R Coll Gen Pract. 1986 December; 36(293): 547-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3668903&dopt=Abstract

6

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

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A serological study of whooping cough. Author(s): Chavan AS, Sant MV. Source: Indian J Pediatr. 1970 July; 37(270): 321-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4320830&dopt=Abstract

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A study of the incidence and mortality of measles and whooping cough in Glasgow from 1855, with reference to birth rates, death rates and death rates of children under one year. Author(s): Wilson TS. Source: Health Bull (Edinb). 1971 October; 29(4): 206-13. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4940067&dopt=Abstract

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ABC of 1 to 7: whooping cough. Author(s): Miller DL, Ross EM. Source: British Medical Journal (Clinical Research Ed.). 1982 June 19; 284(6332): 1874. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6805740&dopt=Abstract

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ABC of 1 to 7: whooping cough. Author(s): Valman HB. Source: British Medical Journal (Clinical Research Ed.). 1982 March 20; 284(6319): 886-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6802339&dopt=Abstract

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Acellular vaccines for preventing whooping cough in children. Author(s): Tinnion ON, Hanlon M. Source: Cochrane Database Syst Rev. 2000; (2): Cd001478. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796648&dopt=Abstract

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Altitude treatment for whooping cough. Author(s): Hall D. Source: Bmj (Clinical Research Ed.). 1991 July 6; 303(6793): 58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1859970&dopt=Abstract

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Altitude treatment for whooping cough. Author(s): Casey PA. Source: Bmj (Clinical Research Ed.). 1991 May 18; 302(6786): 1212. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2043838&dopt=Abstract

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An attempt to correlate whooping cough frequency rates with proportion of vaccinated in a child population. Author(s): Zakharova MS, Novikova OM, Yermakov SP, Sukhov YV. Source: J Hyg Epidemiol Microbiol Immunol. 1977; 21(2): 128-35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=562366&dopt=Abstract

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An evaluation of whooping cough vaccination in Oxford. Author(s): Warin JF. Source: R Soc Health J. 1968 January; 88(1): 21-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5653435&dopt=Abstract

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An outbreak of whooping cough in a highly vaccinated urban community. Author(s): Strebel P, Hussey G, Metcalf C, Smith D, Hanslo D, Simpson J. Source: Journal of Tropical Pediatrics. 1991 March; 37(2): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2027168&dopt=Abstract

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Analysis of antibody profiles in children with whooping cough. Author(s): Novotny P, Macaulay ME, Hart TC, Skvaril F. Source: Dev Biol Stand. 1991; 73: 267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1778318&dopt=Abstract

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Analysis of the cases of typhoid, diphtheria, tetanus, whooping cough and poliomyelitis in Pondicherry hospitals in 1967. Author(s): Datta SP. Source: Indian Journal of Medical Sciences. 1968 December; 22(12): 872-6 Passim. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5714553&dopt=Abstract

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Antibiotics for whooping cough. Author(s): Jenkinson D. Source: British Medical Journal. 1980 March 22; 280(6217): 864. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7370699&dopt=Abstract

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Antibodies to filamentous hemagglutinin of Bordetella pertussis and protection against whooping cough in schoolchildren. Author(s): He Q, Viljanen MK, Olander RM, Bogaerts H, De Grave D, Ruuskanen O, Mertsola J. Source: The Journal of Infectious Diseases. 1994 September; 170(3): 705-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8077734&dopt=Abstract

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Antibody against whooping cough in normal population. Author(s): Saran G, Angra SS, Balasubrahmanyan M. Source: The Indian Journal of Medical Research. 1979 July; 70: 5-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=227785&dopt=Abstract

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Antibody responses after vaccination and disease against leukocytosis promoting factor, filamentous hemagglutinin, lipopolysaccharide and a protein binding to complement-fixing antibodies induced during whooping cough. Author(s): Winsnes R, Lonnes T, Mogster B, Berdal BP. Source: Dev Biol Stand. 1985; 61: 353-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2872124&dopt=Abstract

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Antigens in whooping cough vaccine and antibody levels induced by vaccination of children. Author(s): Ashworth LA, Robinson A, Irons LI, Morgan CP, Isaacs D. Source: Lancet. 1983 October 15; 2(8355): 878-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6137697&dopt=Abstract

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Antimicrobial therapy in whooping cough. Author(s): Henry RL, Dorman DC, Skinner JA, Mellis CM. Source: The Medical Journal of Australia. 1981 July 11; 2(1): 27-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6268953&dopt=Abstract

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Application of pulsed field gel electrophoresis to the 1993 epidemic of whooping cough in the UK. Author(s): Syedabubakar SN, Matthews RC, Preston NW, Owen D, Hillier V. Source: Epidemiology and Infection. 1995 August; 115(1): 101-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641824&dopt=Abstract

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Asthma and whooping cough. Author(s): Williams WO. Source: J R Coll Gen Pract. 1986 December; 36(293): 574. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3668912&dopt=Abstract

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Attack rates of notified whooping cough in immunised and unimmunised children. Author(s): Noah ND. Source: British Medical Journal. 1976 January 17; 1(6002): 128-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1247742&dopt=Abstract

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Binding of murine antibodies against whole-cell pertussis vaccine or filamentous haemagglutinin by Bordetella pertussis from patients with whooping cough. Author(s): van den Berg BM, Beekhuizen H, Van Furth R, Mooi FR. Source: Scandinavian Journal of Immunology. 2000 May; 51(5): 530-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10792847&dopt=Abstract

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Bordetella pertussis adenylate cyclase activity in nasopharyngeal aspirates for rapid diagnosis of whooping cough in relation to culture and serology. Author(s): Eriksson M, Granstrom G, Wretlind B, Granstrom M, Askelof P. Source: Scandinavian Journal of Infectious Diseases. 1991; 23(6): 731-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1815336&dopt=Abstract

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Bordetella pertussis isolation in general practice: 1977-79 whooping cough epidemic in West Glamorgan. Author(s): Kwantes W, Joynson DH, Williams WO. Source: J Hyg (Lond). 1983 April; 90(2): 149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6300227&dopt=Abstract

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Bordetella pertussis serotypes in a whooping cough outbreak. Author(s): Aftandelians RV, Connor JD. Source: American Journal of Epidemiology. 1974 May; 99(5): 343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4363474&dopt=Abstract

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Can whooping cough be eradicated? Author(s): Kendrick PL. Source: The Journal of Infectious Diseases. 1975 December; 132(6): 707-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1202113&dopt=Abstract

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Cerebellar ataxia following whooping cough. Author(s): Setta F, Baecke M, Jacquy J, Hildebrand J, Monseu G, Manto MU. Source: Clinical Neurology and Neurosurgery. 1999 March; 101(1): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350207&dopt=Abstract

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Clinical course of whooping cough in children younger than six months. Author(s): Trollfors B. Source: Acta Paediatr Scand. 1979 May; 68(3): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=443033&dopt=Abstract

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Clinical forum. 12. Whooping cough. Author(s): Pinchen C. Source: Nurs Mirror. 1982 December 8; 155(23): 24-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6296799&dopt=Abstract

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Clinical study of complications of whooping cough in hospitalized cases. Author(s): Singh RN, Chaudhary SP, Moondra P. Source: Indian Pediatrics. 1977 January; 14(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=863493&dopt=Abstract

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Contra-indications to measles and whooping cough vaccination: reality and mythology. Author(s): Nicoll A. Source: The Practitioner. 1986 June; 230(1416): 593-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3748978&dopt=Abstract

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Control of whooping cough in New Zealand; slow progress. Author(s): Lennon D, Reid S, Holdaway D, Thomas M. Source: N Z Med J. 1995 December 8; 108(1013): 495-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8532232&dopt=Abstract

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Controlling a whooping cough outbreak. Author(s): Peddie B. Source: Nurs N Z. 1998 August; 4(7): 14-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10586720&dopt=Abstract

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Cough syncope: a complication of adult whooping cough. Author(s): Jenkins P, Clarke SW. Source: Br J Dis Chest. 1981 July; 75(3): 311-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7295525&dopt=Abstract

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Could it be whooping cough? Author(s): Sturmberg JP, Watt P. Source: Aust Fam Physician. 1999 February; 28(2): 129-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10048250&dopt=Abstract

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Counterimmunoelectrophoresis in the diagnosis of whooping cough. Author(s): Boreland PC, Gillespie SH. Source: Journal of Clinical Pathology. 1984 August; 37(8): 950-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6088591&dopt=Abstract

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Decision making for routine measles/MMR and whooping cough immunisation. Author(s): Nicoll A, Jenkinson D. Source: Bmj (Clinical Research Ed.). 1988 August 6; 297(6645): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3408985&dopt=Abstract

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Development of the pertussis vaccination programme in England and Wales and its effects on whooping cough morbidity and mortality. Author(s): Griffith AH. Source: Dev Biol Stand. 1979; 43: 91-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=520689&dopt=Abstract

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Diagnosis of whooping cough: a new era with rapid molecular diagnostics. Author(s): Cimolai N, Trombley C, O'Neill D. Source: Pediatric Emergency Care. 1996 April; 12(2): 91-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8859915&dopt=Abstract

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Diagnosis of whooping cough--a comparison of culture, immunofluorescence and serology with ELISA. Author(s): Hakansson S, Sundin CG, Granstrom M, Gastrin B. Source: Scandinavian Journal of Infectious Diseases. 1984; 16(3): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6149614&dopt=Abstract

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Dutch whooping cough epidemic puzzles scientists. Author(s): Sheldon T. Source: Bmj (Clinical Research Ed.). 1998 January 10; 316(7125): 92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9462310&dopt=Abstract

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Effect of pneumonia and whooping cough in childhood on adult lung function. Author(s): Johnston ID, Strachan DP, Anderson HR. Source: The New England Journal of Medicine. 1998 February 26; 338(9): 581-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475765&dopt=Abstract

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Effect of vaccination on severity and dissemination of whooping cough. Author(s): Grob PR, Crowder MJ, Robbins JF. Source: British Medical Journal (Clinical Research Ed.). 1981 June 13; 282(6280): 1925-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6263402&dopt=Abstract

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Effect of whooping cough in infancy on subsequent lung function and bronchial reactivity. Author(s): Johnston ID, Bland JM, Ingram D, Anderson HR, Warner JO, Lambert HP. Source: Am Rev Respir Dis. 1986 August; 134(2): 270-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3740653&dopt=Abstract

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Epitope mapping the Fim2 and Fim3 proteins of Bordetella pertussis with sera from patients infected with or vaccinated against whooping cough. Author(s): Williamson P, Matthews R. Source: Fems Immunology and Medical Microbiology. 1996 February; 13(2): 169-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8731026&dopt=Abstract

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Estimating incidence of whooping cough over time: a cross-sectional recall study of four Swedish birth cohorts. Author(s): Krantz I, Taranger J, Trollfors B. Source: International Journal of Epidemiology. 1989 December; 18(4): 959-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2621033&dopt=Abstract

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Evaluation of betamethasone and isoniazid along with chloramphenicol in the management of whooping cough. Author(s): Chandra H, Rao CS, Karan S, Mathur YC. Source: Indian Pediatrics. 1972 February; 9(2): 70-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5034795&dopt=Abstract

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Evaluation of serologic assays for diagnosis of whooping cough. Author(s): Granstrom G, Wretlind B, Salenstedt CR, Granstrom M. Source: Journal of Clinical Microbiology. 1988 September; 26(9): 1818-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2903178&dopt=Abstract

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Failure to vaccinate against whooping cough. Author(s): Stevens D, Baker R, Hands S. Source: Archives of Disease in Childhood. 1986 April; 61(4): 382-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3707190&dopt=Abstract

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Folk cures for whooping cough. Author(s): Yates E. Source: Nurs Mirror. 1978 January 26; 146(4): 18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=341092&dopt=Abstract

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Genetic studies of the molecular basis of whooping cough. Author(s): Weiss AA, Hewlett EL, Myers GA, Falkow S. Source: Dev Biol Stand. 1985; 61: 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2872097&dopt=Abstract

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Haemophilus influenzae infections and whooping cough. Author(s): Moxon ER, Rappuoli R. Source: Lancet. 1990 June 2; 335(8701): 1324-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1971388&dopt=Abstract

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High admission rate of infants and young children with whooping cough: clinical aspects and preventive implications. Author(s): Forsyth K, Farmer K, Lennon DR. Source: Aust Paediatr J. 1984 May; 20(2): 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6466223&dopt=Abstract

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History of whooping cough in nonvaccinated Swedish children, related to serum antibodies to pertussis toxin and filamentous hemagglutinin. Author(s): Zackrisson G, Taranger J, Trollfors B. Source: The Journal of Pediatrics. 1990 February; 116(2): 190-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2299488&dopt=Abstract

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Hospital admissions for whooping cough in the Oxford Region, 1974-9. Author(s): Goldacre MJ, Harris RI. Source: British Medical Journal (Clinical Research Ed.). 1981 January 10; 282(6258): 106-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6779891&dopt=Abstract

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How common is whooping cough in a nonvaccinating country? Author(s): Isacson J, Trollfors B, Taranger J, Zackrisson G, Lagergard T. Source: The Pediatric Infectious Disease Journal. 1993 April; 12(4): 284-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8483621&dopt=Abstract

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Immunisation against diphtheria, tetanus and whooping cough in childhood. Author(s): Hickling S. Source: N Z Med J. 1966 June; 65(406): 357-62. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5222031&dopt=Abstract

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Immunization against diphtheria, pertussis (whooping cough) and tetanus in Canada: the benefits from the use of adsorbed vaccine. Author(s): Cameron J. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1982 November-December; 73(6): 404-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7159854&dopt=Abstract

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Immunization against whooping cough in Salford: a spatial analysis. Author(s): Gatrell AC. Source: Social Science & Medicine (1982). 1986; 23(10): 1027-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3823970&dopt=Abstract

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Immunization against whooping cough: a neuropathological review. Author(s): Corsellis JA, Janota I, Marshall AK. Source: Neuropathology and Applied Neurobiology. 1983 July-August; 9(4): 261-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6621799&dopt=Abstract

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Immunizing against whooping cough. Author(s): Conkle C. Source: J Ark Med Soc. 1990 November; 87(6): 236-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2150961&dopt=Abstract

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Immunoglobulin E response to pertussis toxin in whooping cough and after immunization with a whole-cell and an acellular pertussis vaccine. Author(s): Hedenskog S, Bjorksten B, Blennow M, Granstrom G, Granstrom M. Source: Int Arch Allergy Appl Immunol. 1989; 89(2-3): 156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2759713&dopt=Abstract

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Impact of whooping cough on patients and their families. Author(s): Birnie D, Benham S, Bhopal RS. Source: British Medical Journal (Clinical Research Ed.). 1985 August 3; 291(6491): 349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3926191&dopt=Abstract

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Impact of whooping cough on patients and their families. Author(s): Johnston ID, Hill M, Anderson HR, Lambert HP. Source: British Medical Journal (Clinical Research Ed.). 1985 June 1; 290(6482): 1636-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3924201&dopt=Abstract

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Improved serodiagnosis of whooping cough caused by Bordetella pertussis by determination of IgG anti-LPF antibody levels. Author(s): Nagel J, de Graaf S, Schijf-Evers D. Source: Dev Biol Stand. 1985; 61: 325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2872120&dopt=Abstract

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Infantile spasms and early immunization against whooping cough. Danish survey from 1970 to 1975. Author(s): Melchior JC. Source: Archives of Disease in Childhood. 1977 February; 52(2): 134-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=836065&dopt=Abstract

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Infection and disease in a group of South Indian families. 8. The incidence and severity of whooping cough. Author(s): Ashabai PV, John TJ, Jayabal P. Source: Indian Pediatrics. 1969 October; 6(10): 645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5383647&dopt=Abstract

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Intensity of exposure and severity of whooping cough. Author(s): Nielsen NM, Hedegaard K, Aaby P. Source: The Journal of Infection. 2001 October; 43(3): 177-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798255&dopt=Abstract

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Internal variation in the uptake of whooping cough immunisation within a Health Authority. Author(s): Janes H. Source: Public Health. 1992 September; 106(5): 367-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1410221&dopt=Abstract

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Interpretation of the contraindications to whooping cough vaccination. Author(s): Hull D. Source: British Medical Journal (Clinical Research Ed.). 1981 November 7; 283(6301): 1231-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6797524&dopt=Abstract

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Investigation into reactions to whooping cough vaccine. Author(s): Bellman MH. Source: Health Visit. 1976 July; 49(7): 215-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8409&dopt=Abstract

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Judge “not satisfied” that whooping cough vaccine causes permanent brain damage. Author(s): Dyer C. Source: British Medical Journal (Clinical Research Ed.). 1988 April 23; 296(6630): 1189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3132253&dopt=Abstract

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Layman's guide to common complaints. 5. Whooping cough. Author(s): Librach I. Source: Nurs Mirror. 1979 August 23; 149(8): 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=257635&dopt=Abstract

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Letter: Immunisation against whooping cough. Author(s): Preston NW. Source: British Medical Journal. 1976 March 27; 1(6012): 770-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1260324&dopt=Abstract

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Letter: Immunisation against whooping cough. Author(s): Stewart GT. Source: British Medical Journal. 1976 March 6; 1(6009): 583. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1260289&dopt=Abstract

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Letter: Immunisation against whooping cough. Author(s): Fox R. Source: British Medical Journal. 1976 February 21; 1(6007): 458-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1252796&dopt=Abstract

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Letter: Immunisation against whooping cough. Author(s): Stewart GT. Source: British Medical Journal. 1976 January 31; 1(6004): 283. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1247822&dopt=Abstract

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Letter: Immunisation against whooping cough. Author(s): Stewart GT. Source: British Medical Journal. 1976 January 10; 1(6001): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1244951&dopt=Abstract

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Letter: Protective activity of whooping-cough convalescent serum and serum-IgA level in mice infected with Bordetella pertussis. Author(s): Pittman M. Source: Lancet. 1976 July 17; 2(7977): 156. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=59233&dopt=Abstract

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Letter: Vaccination against whooping cough. Author(s): Dodge JS. Source: British Medical Journal. 1974 December 28; 4(5947): 768. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4441884&dopt=Abstract

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Limitations of erythromycin in whooping cough. Author(s): Henry R, Dorman D, Skinner J, Mellis C. Source: The Medical Journal of Australia. 1981 July 25; 2(2): 108-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6272070&dopt=Abstract

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Long term respiratory sequelae of whooping cough in a nationally representative sample. Author(s): Britten N, Wadsworth J. Source: British Medical Journal (Clinical Research Ed.). 1986 February 15; 292(6518): 4414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3081115&dopt=Abstract

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Long-term sequelae of whooping cough. Author(s): Williams WO. Source: Journal of the Royal Society of Medicine. 1985 September; 78(9): 707-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4045900&dopt=Abstract

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Lung function in adolescents after uncomplicated whooping cough in childhood. Author(s): Teculescu DB, Aubry C, Pham QT, Locuty J, Deschamps JP, Manciaux M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1989 September; 2(8): 733-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2806496&dopt=Abstract

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Medicine and the media--vaccination against whooping cough. Author(s): Griffith AH. Source: J Biol Stand. 1981 October; 9(4): 475-82. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7033225&dopt=Abstract

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Methods for isolation of Bordetella pertussis from patients with whooping cough. Author(s): Hoppe JE. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1988 October; 7(5): 616-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2461860&dopt=Abstract

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Monitoring infants with whooping cough. Author(s): Day SA. Source: Nurs Times. 1979 March 15; 75(11): Suppl 2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=254081&dopt=Abstract

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Morbidity in whooping cough and measles. Author(s): Conway SP, Phillips RR. Source: Archives of Disease in Childhood. 1989 October; 64(10): 1442-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2817928&dopt=Abstract

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Myths and facts.about whooping cough. Author(s): Munson BL. Source: Nursing. 2002 December; 32(12): 83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512501&dopt=Abstract

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Nasal continuous positive airway pressure in the treatment of whooping cough. Author(s): Theilade D. Source: Anaesthesia. 1979 November-December; 34(10): 1028-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=395852&dopt=Abstract

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Natural course of 500 consecutive cases of whooping cough: a general practice population study. Author(s): Jenkinson D. Source: Bmj (Clinical Research Ed.). 1995 February 4; 310(6975): 299-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7866173&dopt=Abstract

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Neonatal whooping cough treated by a mechanical respirator. Use of Engstrom ventilators in long-term treatment. Author(s): Park-Ross AG. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1966 June 11; 40(21): 495-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5220706&dopt=Abstract

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Neurological complications of whooping cough. Author(s): Rao GR, Sundar PS. Source: Indian Pediatrics. 1972 April; 9(4): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4642606&dopt=Abstract

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Neutralizing antibodies to pertussis toxin in whooping cough. Author(s): Granstrom M, Granstrom G, Gillenius P, Askelof P. Source: The Journal of Infectious Diseases. 1985 April; 151(4): 646-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2857752&dopt=Abstract

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New clues to whooping cough pathology. Author(s): Strauss E. Source: Science. 1999 August 6; 285(5429): 811, 813. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454926&dopt=Abstract

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No respiratory sequelae from whooping cough. Author(s): Davies DP. Source: British Medical Journal (Clinical Research Ed.). 1985 September 21; 291(6498): 826-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3929959&dopt=Abstract

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No respiratory sequelae from whooping cough. Author(s): Agerholm M. Source: British Medical Journal (Clinical Research Ed.). 1985 August 10; 291(6492): 409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3926215&dopt=Abstract

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Occasional sporadic cases of whooping cough-like syndrome associated with adenoviral infection: contrast with epidemic whooping cough caused by Bordetella pertussis. Author(s): Kendrick PL. Source: Health Lab Sci. 1971 October; 8(4): 194-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4329891&dopt=Abstract

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On the aetiology of whooping cough. Author(s): Lewis FA, Gust ID, Bennett NM. Source: J Hyg (Lond). 1973 March; 71(1): 139-44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4348453&dopt=Abstract

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Outbreak of whooping cough in general practice. Author(s): Jenkinson D. Source: British Medical Journal. 1978 August 19; 2(6136): 577-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=698598&dopt=Abstract

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Partial remission of nephrotic syndrome during whooping cough. Author(s): Linne T, Wasserman J. Source: Acta Paediatr Scand. 1987 July; 76(4): 667-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3630685&dopt=Abstract

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Pertussis (whooping cough) toxin and Bordetella pertussis whole-cell antibody levels in a healthy New Zealand population. Author(s): Lau RC. Source: N Z Med J. 1989 October 25; 102(878): 560-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2554227&dopt=Abstract

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Pertussis (whooping cough). The GP view. Author(s): Muecke DS. Source: Aust Fam Physician. 1982 March; 11(3): 189-91, 193. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7073627&dopt=Abstract

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Pertussis (whooping cough). The specialist view. Author(s): Beare TH. Source: Aust Fam Physician. 1982 March; 11(3): 194-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7073628&dopt=Abstract

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Pertussis agglutinins and complement fixing antibodies in whooping cough. Author(s): Agarwal KC, Ray M, Chitkara NL. Source: Prog Drug Res. 1975; 19: 178-88. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1219882&dopt=Abstract

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Pertussis antibodies in whooping cough. Author(s): Agarwal KC, Ray M, Chitkara NL, Walia BN. Source: The Indian Journal of Medical Research. 1975 April; 63(4): 533-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=175002&dopt=Abstract

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Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis. Author(s): Pittman M. Source: Reviews of Infectious Diseases. 1979 May-June; 1(3): 401-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=233166&dopt=Abstract

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Pertussis vaccination and pseudo whooping cough. Author(s): Stott NC, Davis RH. Source: British Medical Journal (Clinical Research Ed.). 1981 June 6; 282(6279): 1871. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6786658&dopt=Abstract

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Pertussis vaccine and whooping cough as risk factors in acute neurological illness and death in young children. Author(s): Miller D, Wadsworth J, Diamond J, Ross E. Source: Dev Biol Stand. 1985; 61: 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3879684&dopt=Abstract

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Preferential increase of a T-cell subset as a cause of lymphocytosis in children with whooping cough. Author(s): De Martino M, Rossi ME, Muccioli AT, Ulivelli A, Vierucci A. Source: Boll Ist Sieroter Milan. 1984; 63(5): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6335661&dopt=Abstract

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Progress towards the development of new vaccines against whooping cough. Author(s): Rappuoli R, Podda A, Pizza M, Covacci A, Bartoloni A, de Magistris MT, Nencioni L. Source: Vaccine. 1992; 10(14): 1027-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1471424&dopt=Abstract

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Progress with a recombinant whooping cough vaccine: a review. Author(s): Burnette WN, Mar VL, Whiteley DW, Bartley TD. Source: Journal of the Royal Society of Medicine. 1992 May; 85(5): 285-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1433093&dopt=Abstract

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Prolonged hospital stay for whooping cough: the need for prevention. Author(s): Harker P, Hall E. Source: Public Health. 1982 July; 96(4): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7134373&dopt=Abstract

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Quantitation of circulating T and B lymphocytes in children with whooping cough. Author(s): Bernales R, Eastman J, Kaplan J. Source: Pediatric Research. 1976 December; 10(12): 965-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1087001&dopt=Abstract

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Rapid diagnosis of whooping cough using monoclonal antibody. Author(s): Boreland PC, Gillespie SH, Ashworth LA. Source: Journal of Clinical Pathology. 1988 May; 41(5): 573-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2898488&dopt=Abstract

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Re: “Whooping cough and whooping cough vaccine: the risks and benefits debate”. Author(s): Stewart GT. Source: American Journal of Epidemiology. 1984 January; 119(1): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6691330&dopt=Abstract

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Reactions to whooping cough vaccine. Author(s): Stephenson JB. Source: British Medical Journal. 1979 October 13; 2(6195): 933. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=519234&dopt=Abstract

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Reactions to whooping cough vaccine. Author(s): Brown PE. Source: British Medical Journal. 1979 October 13; 2(6195): 932-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=519232&dopt=Abstract

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Reactions to whooping cough vaccine. Author(s): Robertson JS. Source: British Medical Journal. 1979 September 22; 2(6192): 735. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=509090&dopt=Abstract

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Reading attainment and physical development after whooping cough. Author(s): Johnston ID, Anderson HR, Lambert HP, Patel S. Source: Journal of Epidemiology and Community Health. 1985 December; 39(4): 314-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4086962&dopt=Abstract

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Recognising whooping cough. Author(s): Preston NW. Source: British Medical Journal (Clinical Research Ed.). 1986 March 29; 292(6524): 901-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2870757&dopt=Abstract

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Recognising whooping cough. Author(s): Marcovitch H. Source: British Medical Journal (Clinical Research Ed.). 1986 February 8; 292(6517): 3601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3080169&dopt=Abstract

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Relation between vaccination and notification rates for whooping cough in England and Wales. Author(s): Pollard R. Source: Lancet. 1980 May 31; 1(8179): 1180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6103996&dopt=Abstract

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Respiratory sequelae and lung function after whooping cough in infancy. Author(s): Krantz I, Bjure J, Claesson I, Eriksson B, Sixt R, Trollfors B. Source: Archives of Disease in Childhood. 1990 June; 65(6): 569-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2378512&dopt=Abstract

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Respiratory sequelae of whooping cough. Author(s): Johnston ID, Bland JM, Anderson HR, Lambert HP. Source: British Medical Journal (Clinical Research Ed.). 1985 August 17; 291(6493): 482-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3926244&dopt=Abstract

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Return of whooping cough. Author(s): Church M. Source: British Medical Journal. 1979 January 20; 1(6157): 195. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=421012&dopt=Abstract

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Salbutamol in the treatment of whooping cough. Author(s): Mertsola J, Viljanen MK, Ruuskanen O. Source: Scandinavian Journal of Infectious Diseases. 1986; 18(6): 593-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3810052&dopt=Abstract

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Serious consequences of whooping cough in asthmatic child. Author(s): Thomson AH, Simpson H. Source: Journal of the Royal Society of Medicine. 1986 January; 79(1): 59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3944825&dopt=Abstract

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Serologic diagnosis of whooping cough by an enzyme-linked immunosorbent assay using fimbrial hemagglutinin as antigen. Author(s): Granstrom M, Granstrom G, Lindfors A, Askelof P. Source: The Journal of Infectious Diseases. 1982 December; 146(6): 741-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6128367&dopt=Abstract

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Serologic diagnosis of whooping cough by enzyme-linked immunosorbent assay. Author(s): Conway SP, Balfour AH, Ross H. Source: The Pediatric Infectious Disease Journal. 1988 August; 7(8): 570-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2902556&dopt=Abstract

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Serological correlates in whooping cough. Author(s): Granstrom M, Granstrom G. Source: Vaccine. 1993; 11(4): 445-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8470429&dopt=Abstract

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Serological diagnosis of whooping cough. Author(s): Finger H, Wirsing von Koenig CH. Source: Dev Biol Stand. 1985; 61: 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2872121&dopt=Abstract

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Serological types of whooping cough bacteria and their connection with immunity in vaccinated children. Author(s): Demina AA, Devyatkina NP, Voloshina LZ, Larina LI, Semina NA, Venglinskaya EA, Kostyukova KP. Source: J Hyg Epidemiol Microbiol Immunol. 1973 March; 17(3): 304-15. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4355335&dopt=Abstract

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Serum protein fractionogram in whooping cough. Author(s): Mansharamani RK. Source: Indian Pediatrics. 1966 March; 3(3): 104-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5932761&dopt=Abstract

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Severity of notified whooping cough. Author(s): Miller CL, Fletcher WB. Source: British Medical Journal. 1976 January 17; 1(6002): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1247740&dopt=Abstract

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Severity of whooping cough in England before and after the decline in pertussis immunisation. Author(s): Pollock TM, Miller E, Lobb J. Source: Archives of Disease in Childhood. 1984 February; 59(2): 162-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6322706&dopt=Abstract

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Smiles about rickets, gloom over whooping cough. Author(s): Badminton RM. Source: British Medical Journal (Clinical Research Ed.). 1982 April 24; 284(6324): 1264. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6803932&dopt=Abstract

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Smiles about rickets, gloom over whooping cough. Author(s): Stephens WP. Source: British Medical Journal (Clinical Research Ed.). 1982 February 27; 284(6316): 6601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6802277&dopt=Abstract

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Specific IgE-antibodies to Bordetella pertussis antigens during whooping cough. Author(s): Wirsing von Koenig CH, Finger H. Source: Lancet. 1989 April 1; 1(8640): 728. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2564540&dopt=Abstract

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Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough. Author(s): Granstrom G, Askelof P, Granstrom M. Source: Journal of Clinical Microbiology. 1988 May; 26(5): 869-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2898484&dopt=Abstract

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Specific immunoglobulin for treatment of whooping cough. Author(s): Granstrom M, Olinder-Nielsen AM, Holmblad P, Mark A, Hanngren K. Source: Lancet. 1991 November 16; 338(8777): 1230-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1682643&dopt=Abstract

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Studies of bacterial disease in West Malaysian Orang Asli (Aborigines): an epidemic of whooping cough. Author(s): Haug NL, Anandan J, Ragan E, Lim TW. Source: Med J Malaya. 1969 March; 23(3): 192-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4240073&dopt=Abstract

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Studies on immunization against whooping cough. Author(s): Andreescu V, Caffe I, Marion M, Ivan I. Source: Arch Roum Pathol Exp Microbiol. 1978 July-December; 37(3-4): 295-302. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=757661&dopt=Abstract

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Subclass compositions of immunoglobulin G to pertussis toxin in patients with whooping cough, in healthy individuals, and in recipients of a pertussis toxoid vaccine. Author(s): Zackrisson G, Lagergard T, Trollfors B. Source: Journal of Clinical Microbiology. 1989 July; 27(7): 1567-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2768444&dopt=Abstract

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Sudden infant death and prevalence of whooping cough in the Swedish and Norwegian communities. Author(s): Lindgren C, Milerad J, Lagercrantz H. Source: European Journal of Pediatrics. 1997 May; 156(5): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9177988&dopt=Abstract

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Surveillance of whooping cough in Czechoslovakia. 3. A method of microtitration of antibodies to B. pertussis by means of three type antigens. Author(s): Maixnerova M, Burianova-Vysoka B, Burian V, Stransky V. Source: J Hyg Epidemiol Microbiol Immunol. 1972; 16(4): 457-66. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4674093&dopt=Abstract

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Surveillance of whooping cough in Czechoslovakia. II. Incidence of antigenic types of B. pertussis in Czechoslovakia in the years 1966-1970. Author(s): Maixnerova M, Burianova-Vysoka B, Stransky V. Source: J Hyg Epidemiol Microbiol Immunol. 1972; 16(3): 267-72. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4342922&dopt=Abstract

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Surveillance of whooping cough should continue. Author(s): Matthews RC, Preston NW, Holden DJ. Source: Bmj (Clinical Research Ed.). 2002 October 19; 325(7369): 904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386054&dopt=Abstract

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Symposium on pertussis immunization, in honor of Dr. Pearl L. Kendrick in her eightieth year: current diagnostic procedures in whooping cough. Author(s): Holwerda J. Source: Health Lab Sci. 1971 October; 8(4): 206-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4329893&dopt=Abstract

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Tetany of the newly born complicated by whooping cough. Author(s): Hayes M. Source: Nurs Mirror Midwives J. 1965 December 10; 121(153): 351-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5174810&dopt=Abstract

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The 1985 national immunisation survey: diphtheria, tetanus, and pertussis (whooping cough) Author(s): Lau RC, Bettelheim KA, Patel AC. Source: N Z Med J. 1988 November 23; 101(858): 797-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3194078&dopt=Abstract

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The cellular immune response to Bordetella pertussis in two children with whooping cough. Author(s): Hafler JP, Pohl-Koppe A. Source: European Journal of Medical Research. 1998 November 17; 3(11): 523-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9810032&dopt=Abstract

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The chest radiograph in whooping cough. Author(s): Bellamy EA, Johnston ID, Wilson AG. Source: Clinical Radiology. 1987 January; 38(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3816065&dopt=Abstract

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The effects of population density and malnutrition on the dynamics of whooping cough. Author(s): Duncan CJ, Duncan SR, Scott S. Source: Epidemiology and Infection. 1998 October; 121(2): 325-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825783&dopt=Abstract

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The general practice management of whooping cough. Author(s): Elliott RB. Source: Drugs. 1977 September; 14(3): 220-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=902614&dopt=Abstract

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The laboratory diagnosis of whooping cough by fluorescent antibody and by culture methods. Author(s): Chalvardjian N. Source: Can Med Assoc J. 1966 August 6; 95(6): 263-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4288082&dopt=Abstract

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The law tries to decide whether whooping cough vaccine causes brain damage: Professor Gordon Stewart gives evidence. Author(s): Stewart GT. Source: British Medical Journal (Clinical Research Ed.). 1986 July 19; 293(6540): 203-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3089449&dopt=Abstract

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The melanophore aggregating response of isolated fish scales: a very rapid and sensitive diagnosis of whooping cough. Author(s): Karlsson JO, Andersson RG, Askelof P, Elwing H, Granstrom M, Grundstrom N, Lundstrom I, Ohman L. Source: Fems Microbiology Letters. 1991 August 1; 66(2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1936946&dopt=Abstract

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The modern face of whooping cough. Author(s): Jenkinson D. Source: The Practitioner. 1995 October; 239(1555): 620-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7494793&dopt=Abstract

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The potency of whooping cough (pertussis) vaccines in Canada. Author(s): Cameron J. Source: J Biol Stand. 1980; 8(4): 297-302. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7204415&dopt=Abstract

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The recurrence of whooping cough: possible implications for assessment of vaccine efficacy. Author(s): Fine PE, Clarkson JA. Source: Lancet. 1982 March 20; 1(8273): 666-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6121976&dopt=Abstract

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The serological diagnosis of whooping cough. Author(s): Macaulay ME. Source: J Hyg (Lond). 1979 August; 83(1): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=222838&dopt=Abstract

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The severity of whooping cough in hospitalised children--is it declining? Author(s): Johnston ID, Anderson HR, Lambert HP. Source: J Hyg (Lond). 1985 April; 94(2): 151-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3989282&dopt=Abstract

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The use of parenteral feeding in whooping cough. Author(s): Sarnaik AP, Pensler L, Gregg RH. Source: Clinical Pediatrics. 1978 May; 17(5): 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=417890&dopt=Abstract

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The whooping cough controversy. To immunize or not to immunize? Author(s): Eastman M. Source: Am Pharm. 1979 January; 19(1): 16-20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=758751&dopt=Abstract

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The whooping cough syndrome: A continuing pediatric problem. Author(s): Islur J, Anglin CS, Middleton PJ. Source: Clinical Pediatrics. 1975 February; 14(2): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=46190&dopt=Abstract

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To the etiology of whooping cough syndrome. Part I: Bacteriological examinations. Author(s): Karenova L, Maixnerova M, Nekolova E. Source: J Hyg Epidemiol Microbiol Immunol. 1984; 28(3): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6092457&dopt=Abstract

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Towards third-generation whooping cough vaccines. Author(s): Rappuoli R, Pizza M, Podda A, De Magistris MT, Nencioni L. Source: Trends in Biotechnology. 1991 July; 9(7): 232-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1370047&dopt=Abstract

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Treatment of whooping cough. Author(s): Dianese G. Source: Lancet. 1982 November 27; 2(8309): 1224. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6128532&dopt=Abstract

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Treatment of whooping cough. Author(s): Barrie H. Source: Lancet. 1982 October 9; 2(8302): 830-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6126706&dopt=Abstract

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Treatment of whooping cough: the facts. Author(s): Broomhall J, Herxheimer A. Source: Archives of Disease in Childhood. 1984 February; 59(2): 185-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6367671&dopt=Abstract

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Trimethoprim and sulphamethoxazole in whooping cough. Author(s): Mahadik NK. Source: Indian Pediatrics. 1977 February; 14(2): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=407156&dopt=Abstract

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Undernotification of whooping cough. Author(s): Evans MR. Source: Bmj (Clinical Research Ed.). 1995 May 20; 310(6990): 1331. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7773065&dopt=Abstract

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Use of pulsed-field gel electrophoresis for epidemiological study of Bordetella pertussis in a whooping cough outbreak. Author(s): de Moissac YR, Ronald SL, Peppler MS. Source: Journal of Clinical Microbiology. 1994 February; 32(2): 398-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8150949&dopt=Abstract

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Vaccination against whooping cough. Author(s): Geffen T. Source: Health Trends. 1981 May; 13(2): 44-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10256496&dopt=Abstract

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Vaccination and notification rates for whooping cough. Author(s): Stewart GT. Source: Lancet. 1980 June 14; 1(8181): 1299. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6104097&dopt=Abstract

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Ventilatory support for children with whooping cough. Experience with children admitted to a paediatric intensive care unit. Author(s): Lewis M, Bush GH. Source: Anaesthesia. 1980 October; 35(10): 979-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7004252&dopt=Abstract

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Whooping cough - viral or bacterial disease? Author(s): Nelson JD. Source: The New England Journal of Medicine. 1970 August 20; 283(8): 428-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4317122&dopt=Abstract

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Whooping cough admissions into the Lagos University Teaching Hospital November 1962 to October 1965. Author(s): Audu IS. Source: West Afr Med J. 1966 August; 15(4): 138-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5916287&dopt=Abstract

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Whooping cough after stopping pertussis immunisation. Author(s): Brown PE. Source: British Medical Journal. 1979 August 18; 2(6187): 444. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=486986&dopt=Abstract

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Whooping cough after stopping pertussis immunisation. Author(s): Jenkinson D. Source: British Medical Journal. 1979 July 21; 2(6183): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=466355&dopt=Abstract

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Whooping cough after stopping pertussis immunisation. Author(s): Ditchburn RK. Source: British Medical Journal. 1979 June 16; 1(6178): 1601-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=466141&dopt=Abstract

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Whooping cough and anaesthesia. Author(s): Sandstrom K, Nilsson K. Source: Paediatric Anaesthesia. 1995; 5(1): 76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8521316&dopt=Abstract

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Whooping cough and Parkinson's disease. The Europarkinson Preparatory Activity Research Group. Author(s): de Pedro-Cuesta J, Gudmundsson G, Abraira V, Gudmundsson G, Love A, Tulinius H, Veiga J, Almazan J, Petersen IJ. Source: International Journal of Epidemiology. 1996 December; 25(6): 1301-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9027539&dopt=Abstract

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Whooping cough and pertussis vaccination. Author(s): Stewart GT. Source: British Medical Journal (Clinical Research Ed.). 1984 January 21; 288(6412): 232-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6419866&dopt=Abstract

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Whooping cough and pertussis vaccine. Author(s): Stewart GJ. Source: British Medical Journal (Clinical Research Ed.). 1983 November 12; 287(6403): 1470. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6416462&dopt=Abstract

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Whooping cough and pertussis vaccine. Author(s): Stewart GT. Source: British Medical Journal (Clinical Research Ed.). 1983 July 23; 287(6387): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6409280&dopt=Abstract

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Whooping cough and pertussis vaccine: a comparison of risks and benefits in Britain during the period 1968-83. Author(s): Stewart GT. Source: Dev Biol Stand. 1985; 61: 395-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3835080&dopt=Abstract

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Whooping cough and raised intracranial pressure. Author(s): Forsyth K. Source: Pediatr Infect Dis. 1984 July-August; 3(4): 369-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6473142&dopt=Abstract

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Whooping cough and unrecognised postperinatal mortality. Author(s): Nicoll A, Gardner A. Source: Archives of Disease in Childhood. 1988 January; 63(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3126714&dopt=Abstract

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Whooping cough and whooping cough vaccine: the risks and benefits debate. Author(s): Miller DL, Alderslade R, Ross EM. Source: Epidemiologic Reviews. 1982; 4: 1-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6128242&dopt=Abstract

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Whooping cough antibody. Author(s): Lau R. Source: N Z Med J. 1989 March 8; 102(863): 113. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2538785&dopt=Abstract

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Whooping cough associated with Bordetella parapertussis in a human immunodeficiency virus-infected child. Author(s): Nordmann P, Francois B, Menozzi FD, Commare MC, Barois A. Source: The Pediatric Infectious Disease Journal. 1992 March; 11(3): 248. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1565547&dopt=Abstract

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Whooping cough caused by Bordetella pertussis and Bordetella parapertussis in an immunized population. Author(s): He Q, Viljanen MK, Arvilommi H, Aittanen B, Mertsola J. Source: Jama : the Journal of the American Medical Association. 1998 August 19; 280(7): 635-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9718056&dopt=Abstract

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Whooping cough diagnosis: a clinical evaluation of complementing culture and immunofluorescence with enzyme-linked immunosorbent assay of pertussis immunoglobulin A in nasopharyngeal secretions. Author(s): Campbell PB, Masters PL, Rohwedder E. Source: Journal of Medical Microbiology. 1988 December; 27(4): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2904501&dopt=Abstract

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Whooping cough epidemics in London, 1701-1812: infection dynamics, seasonal forcing and the effects of malnutrition. Author(s): Duncan CJ, Duncan SR, Scott S. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 1996 April 22; 263(1369): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8637925&dopt=Abstract

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Whooping cough immunisation for children with cerebral irritation or damage in the neonatal period. Author(s): Elliman D. Source: British Medical Journal (Clinical Research Ed.). 1986 December 13; 293(6561): 1569. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3099964&dopt=Abstract

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Whooping cough immunisation for children with cerebral irritation or damage in the neonatal period. Author(s): Lingam S, Miller CL, Pateman J. Source: British Medical Journal (Clinical Research Ed.). 1986 November 8; 293(6556): 1237. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3096445&dopt=Abstract

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Whooping cough immunity. Author(s): Thomas MG. Source: N Z Med J. 1989 January 25; 102(860): 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2536476&dopt=Abstract

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Whooping cough immunization in France and Britain: discussion paper. Author(s): Ross EM, Edouard L. Source: Journal of the Royal Society of Medicine. 1983 May; 76(5): 374-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6864704&dopt=Abstract

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Whooping cough immunization. Author(s): Hamilton DG. Source: The Medical Journal of Australia. 1979 December 15; 2(12): 651. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=395431&dopt=Abstract

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Whooping cough immunization. Author(s): Cameron J. Source: British Medical Journal. 1970 January 10; 1(688): 109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5411433&dopt=Abstract

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Whooping cough in a remote area of Mexico. Author(s): Schlenker TL. Source: Wis Med J. 1988 June; 87(6): 14-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3400254&dopt=Abstract

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Whooping cough in adults. Author(s): Williams WO. Source: British Medical Journal (Clinical Research Ed.). 1981 October 24; 283(6299): 1122. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6794786&dopt=Abstract

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Whooping cough in adults. Author(s): Trollfors B, Rabo E. Source: British Medical Journal (Clinical Research Ed.). 1981 September 12; 283(6293): 696-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6793129&dopt=Abstract

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Whooping cough in Fiji. Author(s): Pollard R. Source: Lancet. 1983 June 18; 1(8338): 1381. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6134156&dopt=Abstract

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Whooping cough in Finland 1920-1978. Statistical and epidemiological studies. Author(s): Huovila R. Source: Acta Paediatr Scand Suppl. 1982; 298: 1-29. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6305107&dopt=Abstract

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Whooping cough in Glasgow 1969-80. Author(s): Walker E, Pinkerton IW, Love WC, Chaudhuri AK, Datta JB. Source: The Journal of Infection. 1981 June; 3(2): 150-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6309971&dopt=Abstract

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Whooping cough in Hertfordshire. Author(s): Church MA. Source: Lancet. 1979 October 20; 2(8147): 857-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=90957&dopt=Abstract

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Whooping cough in Hertfordshire. Author(s): Stewart GT. Source: Lancet. 1979 September 1; 2(8140): 473-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=89535&dopt=Abstract

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Whooping cough in infancy. Author(s): Allen W, Barnes CC. Source: The Western Journal of Medicine. 1992 December; 157(6): 681-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1475964&dopt=Abstract

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Whooping cough in infancy. Author(s): O'Grady R, Dolan T. Source: The American Journal of Nursing. 1976 January; 76(1): 114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=174428&dopt=Abstract

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Whooping cough in late pregnancy. Author(s): Granstrom G, Granstrom M, Sterner G. Source: Scand J Infect Dis Suppl. 1990; 71: 27-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2287912&dopt=Abstract

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Whooping cough in Melbourne. Author(s): Bennett NM. Source: The Medical Journal of Australia. 1973 September 8; 2(10): 481-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4356272&dopt=Abstract

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Whooping cough in northern Israel. Author(s): Shmilovitz M, Preston NW, Zaltser H, Cahana A. Source: Isr J Med Sci. 1972 December; 8(12): 1936-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4347731&dopt=Abstract

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Whooping cough in nursery school children. Author(s): Roberts A, Williams WO. Source: J R Coll Gen Pract. 1981 August; 31(229): 470-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7328524&dopt=Abstract

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Whooping cough in relation to other childhood infections in 1977-9 in the United Kingdom. Author(s): Stewart GT. Source: Journal of Epidemiology and Community Health. 1981 June; 35(2): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7299339&dopt=Abstract

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Whooping cough in Scotland--the next epidemic. Author(s): Christie P, O'Brien S. Source: Health Bull (Edinb). 1997 September; 55(5): 292-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769107&dopt=Abstract

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Whooping cough in Shetland. Author(s): Stewart GT. Source: British Medical Journal. 1979 May 19; 1(6174): 1352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=445062&dopt=Abstract

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Whooping cough in spite of immunization. Author(s): Mathias RG. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1978 March-April; 69(2): 130-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=657067&dopt=Abstract

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Whooping cough in Stuttgart. Author(s): Enders G, Rapp I, Biber M, Preston NW, Carter EJ. Source: Lancet. 1988 May 14; 1(8594): 1113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2896947&dopt=Abstract

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Whooping cough in Sudanese children. Author(s): Abdalla BA, Salih MA, Yousif EA, Omer MI. Source: East Afr Med J. 1998 June; 75(6): 353-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803620&dopt=Abstract

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Whooping cough in the United Kingdom 1977-8. Author(s): Stewart GT. Source: British Medical Journal. 1980 August 9; 281(6237): 451-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7427308&dopt=Abstract

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Whooping cough in the United States and Britain. Author(s): Stewart GT. Source: The New England Journal of Medicine. 1983 February 24; 308(8): 464-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6823264&dopt=Abstract

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Whooping cough in Uganda. Author(s): Bwibo NO. Source: Scandinavian Journal of Infectious Diseases. 1971; 3(1): 41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5099426&dopt=Abstract

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Whooping cough in Wear Valley 1983 and 1984: a case control study. Author(s): Pugh EJ, Henson E. Source: Public Health. 1986 January; 100(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3749433&dopt=Abstract

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Whooping cough in West Germany. Author(s): Hoppe JE, Preston NW. Source: Lancet. 1985 October 5; 2(8458): 776. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2864505&dopt=Abstract

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Whooping cough in West London. Author(s): Cunningham D. Source: Lancet. 1983 January 1; 1(8314-5): 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6129397&dopt=Abstract

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Whooping cough infection. Author(s): Cook IF. Source: Aust Fam Physician. 1999 June; 28(6): 540. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399383&dopt=Abstract

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Whooping cough infection. Author(s): Skalla J. Source: Aust Fam Physician. 1999 June; 28(6): 539; Discussion 539-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399382&dopt=Abstract

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Whooping cough makes global comeback. Author(s): Das P. Source: The Lancet Infectious Diseases. 2002 June; 2(6): 322. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144890&dopt=Abstract

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Whooping cough morbidity--a continuing problem. Author(s): Ryan C. Source: Ir Med J. 1980 February; 73(2): 79-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7364559&dopt=Abstract

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Whooping cough surveillance in the north west of England. Author(s): Devine MJ, Bellis MA, Tocque K, Syed Q. Source: Commun Dis Public Health. 1998 June; 1(2): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9644126&dopt=Abstract

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Whooping cough vaccination. Author(s): Grist NR. Source: British Medical Journal. 1977 February 26; 1(6060): 573. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=843811&dopt=Abstract

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Whooping cough vaccination. A worrying decision for parents. Author(s): Harding CM, Bolden KJ. Source: The Practitioner. 1983 February; 227(1376): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6866920&dopt=Abstract

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Whooping cough vaccination: a review of the controversy since the 1981 DHSS report. Author(s): Harding CM. Source: Child: Care, Health and Development. 1983 September-October; 9(5): 257-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6357527&dopt=Abstract

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Whooping cough vaccination: some reasons for non-completion. Author(s): Clarke SJ. Source: Journal of Advanced Nursing. 1980 May; 5(3): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6900639&dopt=Abstract

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Whooping cough vaccination: the case presented by the British national press. Author(s): Harding CM. Source: Child: Care, Health and Development. 1985 January-February; 11(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3995690&dopt=Abstract

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Whooping cough vaccine at birth. Author(s): Abayomi I, Woodland M, Morley D. Source: J Trop Pediatr Environ Child Health. 1973 September; 19(1): 3-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4490499&dopt=Abstract

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Whooping cough vaccine efficacy. Author(s): Preston NW. Source: Lancet. 1982 April 10; 1(8276): 860. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6122091&dopt=Abstract

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Whooping cough vaccine in perspective. Author(s): Miller D, Ross E. Source: Nurs Times. 1981 May 28; 77(22): 937-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6909818&dopt=Abstract

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Whooping cough vaccine on trial again. Author(s): Dyer C. Source: British Medical Journal (Clinical Research Ed.). 1987 October 24; 295(6605): 10534. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3120869&dopt=Abstract

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Whooping cough vaccine research revs up. Author(s): Sun M. Source: Science. 1985 March 8; 227(4691): 1184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2858128&dopt=Abstract

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Whooping cough vaccine. Author(s): Mercer H. Source: Journal of Paediatrics and Child Health. 1990 February; 26(1): 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2331423&dopt=Abstract

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Whooping cough vaccines: where next? Author(s): Elliman D. Source: Child: Care, Health and Development. 1998 July; 24(4): 259-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9693854&dopt=Abstract

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Whooping cough. Author(s): Parry WH. Source: Nurs Times. 1965 November 12; 61(46): 1534-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5839332&dopt=Abstract

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Whooping cough. Author(s): Radbill SX. Source: Am J Dis Child. 1986 June; 140(6): 506-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3706224&dopt=Abstract

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Whooping cough. Author(s): Jenkinson D, Pepper JD. Source: The Practitioner. 1982 September; 226(1371): 1479-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7145809&dopt=Abstract

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Whooping cough. Author(s): Ash D. Source: The Medical Journal of Australia. 1982 May 1; 1(9): 369-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7087872&dopt=Abstract

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Whooping cough. Author(s): Jenkinson D. Source: British Medical Journal. 1978 September 23; 2(6141): 896. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=213156&dopt=Abstract

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Whooping cough. Author(s): Capstick I. Source: British Medical Journal. 1978 May 6; 1(6121): 1214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=638698&dopt=Abstract

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Whooping cough. Author(s): Harper JR. Source: Nurs Times. 1976 December 23-30; 72(51): 1996-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1012952&dopt=Abstract

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Whooping cough. Author(s): Jamieson WM. Source: British Medical Journal. 1973 January 27; 1(5847): 223-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4346857&dopt=Abstract

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Whooping cough. Duty of care. Author(s): Martin A. Source: Nurs Times. 1977 August 11; 73(32): Suppl 20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=909837&dopt=Abstract

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Whooping cough: a shot in the dark. Author(s): Miller DL, Ross EM. Source: British Medical Journal (Clinical Research Ed.). 1983 June 4; 286(6380): 1817-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6407577&dopt=Abstract

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Whooping cough: an answer? Author(s): Marion G. Source: Can Med Assoc J. 1981 April 1; 124(7): 854. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7214285&dopt=Abstract

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Whooping cough: Christchurch 1982. Author(s): Bourchier D, Abbott GD, Fieldes KJ. Source: N Z Med J. 1983 September 14; 96(739): 671-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6577336&dopt=Abstract

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Whooping cough: diagnosis, prevalence and prevention. Author(s): Hansman DJ. Source: The Medical Journal of Australia. 1987 May 18; 146(10): 511-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3574175&dopt=Abstract

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Whooping cough: how the west was won. Author(s): Gelbart M. Source: Nurs Times. 1999 October 6-12; 95(40): 52-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10745844&dopt=Abstract

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Whooping cough: infection and disease. Author(s): Cameron J. Source: Lancet. 1982 June 5; 1(8284): 1301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6123036&dopt=Abstract

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Whooping cough: the facts parents have not been told. Author(s): Gillie O. Source: Sunday Times. 1977 March 6; : 6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11648825&dopt=Abstract

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Whooping cough: time to exercise control; let off lightly. Author(s): Valley L. Source: Nurs Mirror. 1982 November 17; 155(20): 44-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6924323&dopt=Abstract

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Whooping cough: what proportion of cases is notified in an epidemic. Author(s): Crombie DL. Source: British Medical Journal (Clinical Research Ed.). 1983 September 10; 287(6394): 760-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6412813&dopt=Abstract

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Whooping cough: what proportion of cases is notified in an epidemic? Author(s): Jenkinson D. Source: British Medical Journal (Clinical Research Ed.). 1983 July 16; 287(6386): 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6409245&dopt=Abstract

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Whooping cough? Author(s): Adey AB. Source: Can Med Assoc J. 1980 June 7; 122(11): 1238. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7388720&dopt=Abstract

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Whooping cough--a continuing problem. Author(s): Crowcroft NS, Britto J. Source: Bmj (Clinical Research Ed.). 2002 June 29; 324(7353): 1537-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089076&dopt=Abstract

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Whooping cough--a neglected disease in southern Africa. Author(s): Ramkissoon A, Coovadia HM, Loening WE. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1989 June 17; 75(12): 560-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2727853&dopt=Abstract

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Whooping cough--a study of severity in hospital cases. Author(s): Robinson DA, Mandal BK, Ironside AG, Dunbar EM. Source: Archives of Disease in Childhood. 1981 September; 56(9): 687-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7294871&dopt=Abstract

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Whooping cough--aspects of pathogenesis and treatment. Author(s): Trollfors B. Source: Acta Otolaryngol Suppl. 1984; 407: 33-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6093425&dopt=Abstract

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Whooping cough--the forgotten cough. Author(s): Phelan PO. Source: The Medical Journal of Australia. 1978 December 16; 2(13): 587. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=732654&dopt=Abstract

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Whooping cough--Waterford Population Survey. Author(s): O'Boyle M. Source: Ir Med J. 1980 February; 73(2): 76-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7364558&dopt=Abstract

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CHAPTER 2. NUTRITION AND WHOOPING COUGH Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and whooping cough.

Finding Nutrition Studies on Whooping Cough 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 “whooping cough” (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 “whooping cough” (or a synonym): •

“Sucrose analgesia” and diphtheria-tetanus-pertussis immunizations at 2 and 4 months. Author(s): Department of Pediatrics, McGill University, Montreal, Canada. Source: Barr, R G Young, S N Wright, J H Cassidy, K L Hendricks, L Bedard, Y Yaremko, J Leduc, D Treherne, S J-Dev-Behav-Pediatr. 1995 August; 16(4): 220-5 0196-206X

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Adjuvant and protective properties of native and recombinant Bordetella pertussis adenylate cyclase toxin preparations in mice. Author(s): Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Glasgow University, UK. Source: Hormozi, K Parton, R Coote, J FEMS-Immunol-Med-Microbiol. 1999 April; 23(4): 273-82 0928-8244

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ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis. Author(s): Department of Medical Microbiology, Stanford University, CA 94305. Source: Black, W J Munoz, J J Peacock, M G Schad, P A Cowell, J L Burchall, J J Lim, M Kent, A Steinman, L Falkow, S Science. 1988 April 29; 240(4852): 656-9 0036-8075

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Alteration of intracellular cAMP levels and beating rates of cultured chick cardiac cells by Bordetella pertussis adenylate cyclase. Source: Selfe, S Hunter, D D Shattuck, R L Nathanson, N M Storm, D R Mol-Pharmacol. 1987 May; 31(5): 529-34 0026-895X

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Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses. Author(s): Laboratory of Immunology, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. [email protected] Source: Mascart, F Verscheure, V Malfroot, A Hainaut, M Pierard, D Temerman, S Peltier, A Debrie, A S Levy, J Del Giudice, G Locht, C J-Immunol. 2003 February 1; 170(3): 1504-9 0022-1767

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Coupling of muscarinic m1, m2 and m3 acetylcholine receptors, expressed in Chinese hamster ovary cells, to pertussis toxin-sensitive/insensitive guanine nucleotidebinding proteins. Author(s): Department of Cell Physiology and Pharmacology, University of Leicester, UK. Source: Burford, N T Tobin, A B Nahorski, S R Eur-J-Pharmacol. 1995 April 28; 289(2): 343-51 0014-2999

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Discrimination of Bordetella parapertussis and Bordetella pertussis organisms from clinical isolates by PCR using biotin-labelled oligonucleotide probes. Author(s): Kinderklinik Universitatsklinikum, Aachen, Germany. [email protected] Source: Muller, F M Heininger, U Schnitzler, N Kockelkorn, P Cloot, O Lorenz, C Haase, G Mol-Cell-Probes. 1998 August; 12(4): 213-7 0890-8508

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Evaluation of antibodies elicited by immunization with pertussis toxin. Author(s): Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033. Source: Kaslow, H R Schlotterbeck, J D Gotto, J Dev-Biol-Stand. 1991; 73143-50 0301-5149

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Heparin-inhibitable lectin activity of the filamentous hemagglutinin adhesin of Bordetella pertussis. Author(s): Laboratoire de Microbiologie Genetique et Moleculaire INSERM CJF 9109, Institut Pasteur, Lille, France. Source: Menozzi, F D Mutombo, R Renauld, G Gantiez, C Hannah, J H Leininger, E Brennan, M J Locht, C Infect-Immun. 1994 March; 62(3): 769-78 0019-9567

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Induction of abnormal respiratory sounds by capsaicin in rats previously infected with Bordetella pertussis. Author(s): Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, UK. [email protected] Source: Parton, R Hall, E Wardlaw, A C FEMS-Immunol-Med-Microbiol. 1998 February; 20(2): 139-44 0928-8244

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Receptor analogs and monoclonal antibodies that inhibit adherence of Bordetella pertussis to human ciliated respiratory epithelial cells. Author(s): Laboratory of Microbiology, Rockefeller University, New York, New York 10021. Source: Tuomanen, E Towbin, H Rosenfelder, G Braun, D Larson, G Hansson, G C Hill, R J-Exp-Med. 1988 July 1; 168(1): 267-77 0022-1007

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Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethylL-arginine in mice intranasally infected. Author(s): Division of Infectious Diseases, Regional Hospital, Varese, Italy. [email protected] Source: Torre, D Speranza, F Pugliese, A Fassina, G Osculati, A Perversi, L Banfi, M G Airoldi, M Mediators-Inflamm. 1999; 8(1): 25-9 0962-9351

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Role of the adrenal medulla in stress-induced hyperinsulinaemia in normal mice and in mice infected with Bordetella pertussis or treated with pertussis toxin. Author(s): Department of Physiology and Pharmacology, University of Strathclyde, Glasgow. Source: Sidey, F M Dean, H G Furman, B L J-Endocrinol. 1988 July; 118(1): 135-40 00220795

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Stimulation of mucosal and systemic antibody responses against Bordetella pertussis filamentous haemagglutinin and recombinant pertussis toxin after nasal administration with chitosan in mice. Author(s): Danbiosyst UK Ltd, Albert Einstein Centre, Highfields Science Park, Nottingham, UK. Source: Jabbal Gill, I Fisher, A N Rappuoli, R Davis, S S Illum, L Vaccine. 1998 December; 16(20): 2039-46 0264-410X

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Surface-associated filamentous hemagglutinin induces autoagglutination of Bordetella pertussis. Author(s): Laboratoire de Microbiologie Genetique et Moleculaire, INSERM CJF 9109, Institut Pasteur, Lille, France. Source: Menozzi, F D Boucher, P E Riveau, G Gantiez, C Locht, C Infect-Immun. 1994 October; 62(10): 4261-9 0019-9567

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The interaction of Ca2+ with the calmodulin-sensitive adenylate cyclase from Bordetella pertussis. Author(s): Department of Pharmacology, School of Medicine, University of Washington, Seattle 98122. Source: Masure, H R Oldenburg, D J Donovan, M G Shattuck, R L Storm, D R J-BiolChem. 1988 May 15; 263(14): 6933-40 0021-9258

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Whooping cough and Parkinson's disease. The Europarkinson Preparatory Activity Research Group. Author(s): Department of Applied Epidemiology, National Care for Epidemiology, Carlos III Institute of Health, Madrid, Spain. Source: de Pedro Cuesta, J Gudmundsson, G Abraira, V Gudmundsson, G Love, A Tulinius, H Veiga, J Almazan, J Petersen, I J Int-J-Epidemiol. 1996 December; 25(6): 130111 0300-5771

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/

Nutrition

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND WHOOPING COUGH Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to whooping cough. 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 whooping cough 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 “whooping cough” (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 whooping cough: •

“Antiwhooping cough potentialities of the flesh of an Indian bird Acridotherus tristis”. Author(s): Rathore HS, Swarup. Source: Indian Journal of Medical Sciences. 1978 March-April; 32(3-4): 40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=569641&dopt=Abstract

•

25 years on--an update on topics selected from the first volume of the Journal. Author(s): Duerden BI. Source: Journal of Medical Microbiology. 1994 September; 41(3): 149-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8064834&dopt=Abstract

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A comparative clinical investigation of chloramphenicol and osteopathic manipulative. Author(s): KURSCHNER OM. Source: J Am Osteopath Assoc. 1958 May; 57(9): 559-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13538778&dopt=Abstract

•

A survey for thirty years' clinical application of cupping. Author(s): Cui J, Zhang GQ. Source: J Tradit Chin Med. 1989 June; 9(2): 151-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2674552&dopt=Abstract

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Current health scenario in rural India. Author(s): Patil AV, Somasundaram KV, Goyal RC. Source: The Australian Journal of Rural Health. 2002 April; 10(2): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047509&dopt=Abstract

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Folk cures for whooping cough. Author(s): Yates E. Source: Nurs Mirror. 1978 January 26; 146(4): 18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=341092&dopt=Abstract

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Folk medicine in Dundee. Author(s): HONEYMAN AM. Source: Medical History. 1960 October; 4: 350. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13715658&dopt=Abstract

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Healing potential of Datura alba on burn wounds in albino rats. Author(s): Priya KS, Gnanamani A, Radhakrishnan N, Babu M. Source: Journal of Ethnopharmacology. 2002 December; 83(3): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426086&dopt=Abstract

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Health care in Africa. Author(s): Brown MS. Source: The Nurse Practitioner. 1984 July; 9(7): 38-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6462542&dopt=Abstract

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Indigenous healers in the North West Province: a survey of their clinical activities in health care in the rural areas. Author(s): Shai-Mahoko SN. Source: Curationis. 1996 December; 19(4): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283340&dopt=Abstract

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Individual and community risks of measles and pertussis associated with personal exemptions to immunization. Author(s): Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE. Source: Jama : the Journal of the American Medical Association. 2000 December 27; 284(24): 3145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135778&dopt=Abstract

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Infectious diseases in the 21st century. Author(s): Kumate J. Source: Archives of Medical Research. 1997 Summer; 28(2): 155-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9204602&dopt=Abstract

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Local massage after vaccination enhances the immunogenicity of diphtheria-tetanuspertussis vaccine. Author(s): Hsu CY, Huang LM, Lee CY, Lin TY, Lee PI, Chen JM. Source: The Pediatric Infectious Disease Journal. 1995 July; 14(7): 567-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7567283&dopt=Abstract

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Maternity care in the Sudd, southern Sudan. Author(s): Bouchier VA. Source: Trop Doct. 1984 January; 14(1): 32-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6729962&dopt=Abstract

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Mothers' management of childhood diseases in Yorubaland: the influence of cultural beliefs. Author(s): Feyisetan BJ, Asa S, Ebigbola JA. Source: Health Transit Rev. 1997 October; 7(2): 221-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10176379&dopt=Abstract

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Pertussis outbreaks in groups claiming religious exemptions to vaccinations. Author(s): Etkind P, Lett SM, Macdonald PD, Silva E, Peppe J. Source: Am J Dis Child. 1992 February; 146(2): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1733146&dopt=Abstract

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Response of parents to five killer diseases among children in a Yoruba community, Nigeria. Author(s): Adetunji JA. Source: Social Science & Medicine (1982). 1991; 32(12): 1379-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1871609&dopt=Abstract

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The Butajira Rural Health Project in Ethiopia: mothers' perceptions and practices in the care of children with acute respiratory infections. Author(s): Muhe L, Kidane Y, Shamebo D, Krantz I, Freij L.

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Source: Int J Health Sci. 1994; 5(3): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12320383&dopt=Abstract •

The folk-lore of pertussis. Author(s): PAUL H. Source: Med World. 1956 March; 84(3): 252-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13308627&dopt=Abstract

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Zinc supplementation as adjunct therapy in children with measles accompanied by pneumonia: a double-blind, randomized controlled trial. Author(s): Mahalanabis D, Chowdhury A, Jana S, Bhattacharya MK, Chakrabarti MK, Wahed MA, Khaled MA. Source: The American Journal of Clinical Nutrition. 2002 September; 76(3): 604-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198006&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to whooping cough; 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 Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Cough Source: Healthnotes, Inc.; www.healthnotes.com Pertussis Source: Integrative Medicine Communications; www.drkoop.com Pyloric Stenosis Source: Integrative Medicine Communications; www.drkoop.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Whooping Cough Source: Integrative Medicine Communications; www.drkoop.com

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Chinese Medicine Baibu Alternative names: Stemona Root; Radix Stemonae Source: Chinese Materia Medica Lusika Wan Alternative names: Lusika Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China

•

Herbs and Supplements Anise Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Arctium Alternative names: Burdock, Gobo; Arctium lappa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Elecampane Alternative names: Inula helenium Source: Healthnotes, Inc.; www.healthnotes.com Elecampane Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Eucalyptus Alternative names: Eucalyptus globulus Source: Healthnotes, Inc.; www.healthnotes.com Grindelia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Horehound Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ivy Leaf Alternative names: Hedera helix Source: Healthnotes, Inc.; www.healthnotes.com Jamaica Dogwood Alternative names: Piscidia erythrina, Piscidia piscipula Source: Integrative Medicine Communications; www.drkoop.com Lobelia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ma Huang Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Mentha Alternative names: Pennyroyal; Mentha/Hedeoma pulegium Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piscidia Erythrina Source: Integrative Medicine Communications; www.drkoop.com Piscidia Piscipula Source: Integrative Medicine Communications; www.drkoop.com

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Red Clover Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Skunk Cabbage Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Sundew Alternative names: Drosera rotundifolia, Drosera ramentacea, Drosera intermedia, Drosera anglica Source: Healthnotes, Inc.; www.healthnotes.com Thyme Alternative names: Thymus vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Thyme Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Wild Cherry Bark Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca

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 WHOOPING COUGH Overview In this chapter, we will give you a bibliography on recent dissertations relating to whooping cough. 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 “whooping cough” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on whooping cough, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Whooping Cough 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 whooping cough. 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: •

Structural and Immunological Studies of Pertussis Toxin: Effect of Toxoiding by Fowler, Sarah; Phd from Open University (united Kingdom), 2002 http://wwwlib.umi.com/dissertations/fullcit/f486769

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

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

Patents on Whooping Cough By performing a patent search focusing on whooping cough, 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. 8Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on whooping cough: •

Amplification and detection of Bordetella pertussis Inventor(s): Hellyer; Tobin J. (Owings Mills, MD), Wood; Janet L. (Perryville, MD) Assignee(s): Becton, Dickinson and Company (Franklin Lakes, NJ) Patent Number: 6,261,785 Date filed: July 27, 2000 Abstract: Amplification primers and methods for specific amplification and detection of a pertussis toxin promoter target are disclosed. The primer-target binding sequences are useful for amplification and detection of Bordetella pertussis target in a variety of amplification and detection reactions. Excerpt(s): The present invention relates to methods for determining the presence or absence of Bordetella pertussis from respiratory samples or other patient specimens, cultures, or environmental samples. The method involves using nucleic acid primers to amplify specifically a pertussis toxin promoter (ptx) target, preferably using one of the techniques of Strand Displacement Amplification (SDA), thermophilic Strand Displacement Amplification (tSDA) or fluorescent real time tSDA. B. pertussis causes whooping cough (pertussis) in humans. Of the several toxins produced by B. pertussis, the pertussis toxin constitutes the main virulence factor as described by A. Weiss, et al. (1984. J. infect. Dis., 150:219-222). Although other members of the genus Bordetellae (B. parapertussis, B. bronchiseptica) contain the pertussis toxin operon, the toxin is not expressed in these species due to mutations in the promoter region (C. Locht, et al., 1986, Science, 232:1258-1264). With appropriate primer design, these mutations confer specificity to the amplification and detection of B. pertussis DNA. Nucleic acid amplification is a powerful technology, which allows rapid detection of specific target sequences. It is therefore a promising technology for the rapid detection and identification of B. pertussis. Examples of identification of B. pertussis using PCR to amplify a variety of genes including sequences of the pertussis toxin promoter gene were reviewed by M. Muller, et al. (1997. Clin. Microbiol. 35, 10:2435-3443). Other examples of the specific identification of B. pertussis using PCR to amplify sequences within the pertussis toxin promoter gene were described by D. Furuya, et al. (1999. Immunopharmacol. Immunotoxicol. 21(1):55-63), D. Farrell, et al. (1999. Abstr. No. 1569. pg. 225. 39.sup.th ICAAC Meet.), T. Ross, et al. (2000. Abstr. No. C-175 pg. 170 100.sup.th Gen. Meet. Am. Soc. Microbiol), and U. Heininger, et al. (2000. Pediatrics 105(3):E31). The oligonucleotide primers of the present invention are applicable to nucleic acid amplification and detection of B. pertussis. Web site: http://www.delphion.com/details?pn=US06261785__

•

Antigenic preparations and isolation of such preparations Inventor(s): Novotny; Pavel (Beckenham, GB2) Assignee(s): Burroughs Wellcome Company (Research Triangle Park, NC) Patent Number: 5,237,052 Date filed: December 9, 1991

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Abstract: The present invention provides novel antigenic preparations comprising proteinaceous material associated with adenylate cyclase activity in cultures of B. pertussis, the said preparations being useful as components of acellular whooping cough vaccines. The invention further provides methods for the isolation of such antigenic preparations. Excerpt(s): The present invention relates to antigenic preparations for use in acellular vaccines against Bordetella pertussis, and to a method for the isolation of such preparations. Bordetella pertussis causes a serious and debilitating disease in humans, children being particularly susceptible, which is kept under control in the developed countries by large scale immunisation programmes. It has been found that immunisation is a very important factor in the reduction of the disease and that failure to vaccinate can lead to increased incidence of the disease. In practically all areas, immunisation is effected using a whole cell B. pertussis vaccine which has been found to be relatively effective in preventing the disease. However, it has been recognised that whole cell vaccines may suffer from several draw-backs. Thus, for example, in about 1 in every 10,000 children inoculated, clinical symptoms occur which may include fever, local reactions and persistent screaming. Further, it would appear that some batches of whole cell vaccine provide no protection at all while still being associated with the possibility of undesirable side-effects. With the currently low occurrence of the disease in developed countries with immunisation programmes, the benefit/risk ratio is poorly defined, and many clinicians believe that the risks of inoculation outweigh the benefits gained by immunisation. As a result, many children are not inoculated and there is then a serious risk of a pandemic of whooping cough. Considerable research effort has, therefore, been directed towards the development of improved pertussis vaccines and especially acellular vaccines which lack the components associated with the toxic effects of the whole cell vaccines hitherto used whilst incorporating those components necessary to protect against the disease. Web site: http://www.delphion.com/details?pn=US05237052__ •

Bordetella pertussis and Bordetella parapertussis strains Inventor(s): Gueirard; Pascale (Meudon la Foret, FR), Guiso; Nicole (Paris, FR) Assignee(s): Institut Pasteur (Paris, FR) Patent Number: 6,030,625 Date filed: April 23, 1998 Abstract: An immunogenic composition, characterized in that it comprises an adenyl cyclase-hemolysin (Ac-Hly) protein, or an immunogenic portion of this AC-Hly, of a strain of Bordetella chosen from B. pertussis, B. parapertussis or B. bronchiseptica, and in that it comprises, in addition, a bacterial extract containing the expression products of the vrg genes of a strain of Bordetella chosen from B. pertussis, B. parapertussis or B. bronchiseptica, or a portion of these expression products which is sufficient to induce an immune response in a host to which the extract might be administered. Excerpt(s): The genus Bordetella comprises four species Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica and Bordetella avium. The bordetellae are Gram-negative coccobacilli responsible for respiratory infections. Bordetella pertussis and Bordetella parapertussis, agents of whooping cough, are strictly human pathogens. Bordetella bronchiseptica is pathogenic for various mammals, and more rarely for man, and, in distinction to B. pertussis and B. parapertussis, is capable of surviving outside

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the host. Bordetella avium is pathogenic only for birds. Since the introduction of whooping cough vaccination in countries where vaccine cover is greater than 80%, it has been possible to observe a dramatic fall in morbidity and mortality. This fall is indeed attributable to vaccination since, in several countries (Great Britain, Sweden, Japan, etc.), deadly epidemics of whooping cough have taken place in the years following the cessation of vaccination. Web site: http://www.delphion.com/details?pn=US06030625__ •

Bordetella pertussis variants Inventor(s): Imaizumi; Atsushi (Hino, JP), Sato; Hiroko (Tokyo, JP), Sato; Yuji (Tokyo, JP), Yoshida; Iwao (Kanonji, JP) Assignee(s): National Institute of Health (Tokyo, JP), Teijin Limited (Osaka, JP) Patent Number: 5,223,255 Date filed: October 11, 1991 Abstract: A Bordetella pertussis variant which produces a pertussis toxin mutant protein partially devoid of subunits. When the variants of the present invention are cultured, a pertussis toxin mutant protein partially devoid of subunits, particularly at least subunit S1, can be harvested from the culture. The thus-obtained pertussis toxin mutant protein partially devoid of subunits can be applied to the preparation of a pertussis vaccine by a conventional method. Excerpt(s): The present invention relates to Bordetella pertussis variants producing a non-toxic but immunogenic pertussis toxin mutant protein, which is applied for preparing a new pertussis vaccine. More particularly, the present invention relates to a Bordetella pertussis phase I variant not having a pertussis toxic activity, but producing a partial antigen protein which induces an antibody for neutralizing the biological activity of pertussis toxin. The pertussis toxin has a molecular weight of about 107 KDa, and is composed of two functionally different parts (A and B) as the bacterial toxin, such as diphtheria toxin and cholera toxin. The part A (subunit 1, S1) is thought to be involved in NAD-dependent ADP-ribosyltransferase activity, and part B (subunit 2, 3, 4(2), 5, S2, S3, S4, S5) is involved in the binding to target cells. A variety of the following physiological activities thereof are known: namely, leukocytosis-promoting activity, histamine sensitizing activity, islet-activating activity, adjuvant activity, mitogen activity, glycerol-releasing activity, vascular permeability stimulating activity, and CHO cell-clustering activity. Based on these physiological activities, pertussis toxin is considered a major pathogenic factor in the occurrence of whooping cough, an infection having a serious effect on infants. Accordingly, pertussis toxin is recognized as an important protective antigen in the preparation of a corresponding pertussis vaccine. Web site: http://www.delphion.com/details?pn=US05223255__

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Bordetella toxin peptides and vaccines Inventor(s): Bartfai; Tamas (Stocksund, SE) Assignee(s): Trion-Forskining-Och Utvecklings Aktiebolag (Sollentuna, SE) Patent Number: 5,225,193 Date filed: May 24, 1989

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Abstract: The following new polypeptides are described: (a) H-X.sup.1 -Asp-Asp-ProPro-Ala-Thr-Val-Tyr-Arg-Tyr-Asp-Ser-Arg-Pro-Pro-Glu-Asp-X.sup.2 -Y, (b) H-X.sup.1 Ser-Glu-Tyr-Leu-Ala-His-Arg-Arg-Ile-Pro-Pro-Glu-Asn-Ile-Arg-Arg-Val-Thr-A rg-ValX.sup.2 -Y, (c) H-X.sup.1 -Ala-Phe-Val-Ser-Thr-Ser-Ser-Ser-Arg-Arg-Tyr-Thr-Glu-ValTyr-X.sup.2 -Y, (d) H-X.sup.1 -Gly-Ile-Thr-Gly-Glu-Thr-Thr-Thr-Thr-Glu-Tyr-Ser-AsnAla-Arg-Tyr-Val-X.sup.2 -Y, and (e) H-X.sup.1 -Leu-Glu-His-Arg-Met-Gln-Glu-Ala-ValGlu-Ala-Glu-Arg-Ala-Gly-Arg-Gly-Thr-G ly-His-Phe-Ile-X.sup.2 -Y, in which X.sup.1 and X.sup.2 each represents an optional coupling-facilitating amino acid residue, and Y represents --OH or --NH.sub.2. Additionally, there is described an artificial pertussis toxin antigen, which mainly consists of at least one peptide sequence reacting with antibodies induced by the native pertussis toxin selected from the above polypeptides (a) to (e) and parts thereof. The above described artificial pertussis toxin antigen is included as a diagnostic antigen in a diagnostic immunoassay kit for the determination of antibodies induced by the native pertussis toxin in a sample of biological fluid, and as an immunizing component in a vaccine composition against whooping cough, respectively. Furthermore there is described an intradermal skin test composition comprising the above described artificial pertussis toxin antigen. Excerpt(s): The present invention relates to new polypeptides, to artificial pertussis toxin antigens, which mainly consist of peptide sequences reacting with antibodies induced by the native pertussis toxin selected from the new polypeptides and parts thereof, to a diagnostic immunoassay kit comprising as a diagnostic antigen, said antigens reacting with antibodies induced by the native pertussis toxin, to a vaccine composition comprising as an immunizing component antigens selected from said antigens reacting with antibodies induced by the native pertussis toxin, and to an intradermal skin test composition comprising antigens selected from said antigens reacting with antibodies induced by the native pertussis toxin. Up to now no peptide antigens constituting part of pertussis toxin have been identified in the art. Since such antigens have not been provided, it has not been possible to develop diagnostic immunoassay kits comprising such antigens as diagnostic antigens nor to develop vaccines against whooping cough based on such antigens. Diagnosis of whooping cough with the aid of antigens directed against Bordetella pertussis antibodies or proteins produced by B. pertussis have been published, but as diagnostic antigen there has been used fimbrial hemagglutinin (see e.g. Granstrom, M., Granstroom, G., Lindfors, A., and Askelof, P. 1982. Serologic diagnosis of whooping cough by an enzyme-linked immunosorbent assay using fimbrial hemagglutinin as antigen. J. Infect. Dis. vol 146:741-745), or sonicated B. pertussis bacteria (see e.g. Goodman, Y. E., Wort, A. J. and Jackson, F. L. 1981. Enzyme-linked immunosorbent assay for detection of pertussis immunoglobulin A in nasopharyngeal secretions as an indicator of recent infection. J. Clin. Microbiol. vol. 13:286-292, and Viljanen, M. K., Ruuskanen, O., Granberg, C. and Salmi, T. T. 1982. Serological diagnosis of pertussis: IgM, IgA and IgG antibodies against Bordetella pertussis measured by enzyme-linked immunosorbent assay. Scand. J. Infect. Dis. vol. 14:112-117). Web site: http://www.delphion.com/details?pn=US05225193__

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Cloning of the gene which codes for the pilinic subunit fim3 of Bordetella pertussis Inventor(s): Cuzzoni; Anna (Pavia, IT), De Ferra; Francesca (San Donato Mil., IT), Grandi; Guido (Segrate, IT), Pedroni; Paola (Milan, IT), Riboli; Barbara (Cremona, IT) Assignee(s): Eniricerche S.P.A. (Milan, IT) Patent Number: 5,525,489 Date filed: March 9, 1993 Abstract: A cloned DNA fragment of Bordetella pertussis including the gene which codes for the pilinic subunit fim3, vectors which contain it and microorganisms transformed by the vectors.The protein and peptides corresponding to at least one epitope of the gene which codes for the pilinic subunit fim3 are particularly useful for the development of acellular anti-pertussis vaccines.In addition, a strain of Bordetella modified by a recombinant replication or genome-integration vector containing the cloned DNA fragment or the gene or a fraction thereof is particularly suitable for the development of a cellular anti-pertussis vaccine. Excerpt(s): The present invention relates to the cloned and sequenced gene which codes for the pilinic subunit fim3 of Bordetella pertussis or a peptide corresponding to at least one epitope thereof, the cloned DNA fragment of Bordetella pertussis including the gene, vectors containing it, microorganisms transformed by the vectors and their use for the development of a vaccine effective against pertussis. Pertussis is a disease of the respiratory tract caused by Bordetella pertussis (B.pertussis), a microorganism which is transmitted from a sick person to a susceptible healthy individual during the catarrhal and convulsive stage (the virulent stage or Stage I). Pertussis may cause convulsions, brain damage and sometimes death, particularly in infants and newborn babies without maternal anti-pertussis antibodies; an effective anti-pertussis vaccine is therefore particularly desirable. Web site: http://www.delphion.com/details?pn=US05525489__

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Efficacious vaccines against bordetella pertussis comprising a combination of individually purified pertussis antigens Inventor(s): Eckhardt; Thomas G. (New Windsor, NY), Gotto; John W. (Suffern, NY), McClintock; David K. (Ramsey, NJ), Scott; Jane V. (Chappaqua, NY) Assignee(s): American Cyanamid Company (Madison, NJ) Patent Number: 5,885,586 Date filed: May 22, 1995 Abstract: This invention is directed to a vaccine for the prevention of disease caused by Bordetella pertussis which comprises the pertussis antigens filamentous hemagglutinin, detoxified lymphocytosis promoting factor and a 69 kilodalton outer membrane protein, where said antigens are individually purified prior to being combined to form the vaccine. The invention is further directed to pertussis vaccines where the antigens are combined in any ratio, including ratios not possible in whole cell or co-purified acellular pertussis vaccines. The pertussis antigens may be further combined with other individually purified pertussis antigens, pertussis structural components, adjuvants, stabilizers and non-pertussis vaccine components. Excerpt(s): This invention relates to vaccines efficacious against Bordetella pertussis which are prepared by individually purifying specific pertussis antigens which are then

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combined to form the vaccine. In addition, the vaccine may contain pertussis structural components and non-pertussis vaccine components. The bacterium Bordetella pertussis is the causative agent of pertussis or whooping cough, a serious and potentially fatal infectious disease of the upper respiratory tract. Pertussis vaccines currently used contain chemically inactivated whole cells of B. pertussis. More recently, acellular pertussis vaccines were developed which are based on material obtained by chemical and physical fractionation of B. pertussis cultures. Whole cell vaccines contain the antigenic components necessary to provide protection from pertussis disease and their efficacy in humans is generally well accepted. However, whole cell vaccines also contain components which are not required for protection. Some of these components, such as endotoxin, have been implicated in undesired effects which may occur coincident with pertussis immunization (Bibliography 1). Web site: http://www.delphion.com/details?pn=US05885586__ •

Filamentous hemagglutinin of B. pertussis Inventor(s): Domenighini; Mario (via Fiorentina 1, 53100 Siena, IT), Falkow; Stanley (8 Longspur, Portola Valley, CA 94025), Rappuoli; Rino (via Calamandrei 37, Quercegrossa, 53100 Siena, IT), Relman; David A. (785 Roble, No. 5, Menlo Park, CA 94025) Assignee(s): none reported Patent Number: 6,036,960 Date filed: September 1, 1994 Abstract: Nucleic acid and protein compositions are provided from B. pertussis which may find use in diagnosis, prevention and therapy of whooping cough. Particularly, an open reading frame encoding filamentous hemagglutinin precursors provided, with the intact protein for the filamentous hemagglutinin portion thereof, can be expressed in a wide variety of hosts, for use in the production of antibodies, for immunodiagnosis or therapy, or as vaccines for prophylactic purposes. Excerpt(s): This invention relates to the gene encoding filamentous hemagglutinin of B. pertussis, the protein product and the use of the gene and the product for developing vaccines by genetic engineering techniques. Bordetella pertussis is a small gram negative bacillus found only in humans. It is the etiologic agent of the childhood disease whooping cough, also known as pertussis. In susceptible individuals, the disease may progress to a serious paroxysmal phase. Violent and spasmodic coughing occurs, with the patient being subject to secondary injury from the hypoxia and convulsions attendant with the coughing paroxysms. Secondary infections, encephalopathy and death may occur. The discrete molecular moiety that has been associated with the severe effects in the paroxysmal stage of the disease is pertussis toxin (PTX). PTX has been reported under a variety of names, including lymphocytosis promoting factor, histamine sensitizing factor and islet-activating protein. Another protein, filamentous hemagglutinin (FHA) is a surface associated protein expressed by B. pertussis under the control of a trans-acting vir locus. FHA, while poorly characterized, is thought to act as a major adhesion and immunodominant antigen in the course of human infection. This protein appears as a heterogeneous collection of polypeptide species on sodium dodecylsulfate-polyacrylamide gel electrophoreses, ranging from approximately 60 to 220 kDa (kilodaltons). It is likely that most of the smaller, commonly seen protein gel bands represent degradation products of a dominant 220 kDa species. Electron

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microscopy of this protein reveals a filamentous structure with dimensions of 2 nm by 40-100 nm. Web site: http://www.delphion.com/details?pn=US06036960__ •

Genes for the export of pertussis holotoxin Inventor(s): Baker; Steven M. (Rochester, NY), Deich; Robert A. (Rochester, NY) Assignee(s): American Cyanamid Company (Parsippany, NJ) Patent Number: 5,643,747 Date filed: March 31, 1994 Abstract: The invention relates to a cloned region of the Bordetella pertussis genome located 3' of the ptx operon encoding factors required for expression, assembly and secretion of pertussis holotoxin. Methods for obtaining increased levels of holotoxin production using homologous and heterologous hosts are also described. Excerpt(s): Bordetella pertussis is the primary causative agent of pertussis, or whooping cough, an acute infection of the respiratory tract. Pertussis occurs worldwide and is most severe when it infects unimmunized infants. Currently available vaccines (whole cell and partially purified acellular) are believed to have approximately 80-90% efficacy in the first few years after immunization. Effective immunization declines, in the case of whole cell vaccines, to almost no efficacy by 12 years postimmunization. The duration of protection provided by the acellular vaccine is unknown. The currently available vaccines are accompanied by a number of adverse reactions, some of which are severe or life-threatening. These severe reactions can include high fever, seizures, a shock-like hypo responsive state, encephalopathy and severe allergic reactions. In addition, individuals completely immunized with these vaccines can still develop pertussis. A purified component vaccine specific to the pertussis holotoxin would be useful for developing specific immunity to B. pertussis while minimizing potential adverse side effects caused by the currently available complex whole-cell or partially purified acellular vaccines. One of the limitations of a purified component B. Pertussis vaccine is the time and expense involved in the growth and processing of large fermentor volumes of B. pertussis required to obtain sufficient amounts of pertussis holotoxin (PT) or mutated forms of the toxin protein, known as cross reactive materials or CRMs. Several investigators have attempted to overcome this limitation by over expression of PT using either homologous expression systems in B. pertussis , or in closely related B. parapertussis or B. bronchiseptica species (Lee, C. K. et al., Infect. Immun. 57:1413-1418 (1989)), or by utilizing heterologous expression systems such as E. coli or B. subtilis (Burnette, W. N. et al., Bio/Technology 699-705 (1988); Locht, C. and J. M. Keith, Science 232:1258-1264 (1986); Nicosia, A., et al., Proc. Natl. Acad. Sci. USA 83:4631 (1986)). Unfortunately, these efforts have failed to provide any system capable of consistently yielding amounts of PT holotoxin significantly greater than the amount obtained from cultures of wild type B. pertussis. The present invention is based upon the identification of a cloned region of the B. pertussis genome. This includes a purified or partially purified nucleic acid sequence comprising an approximately 8 kb region of the B. pertussis genome, defined herein as the pts region, located immediately 3' (downstream) of the B. pertussis ptx operon. This cloned region encodes factors required for efficient expression and secretion of pertussis holotoxin. The nucleic acid sequence comprises at least six genes, designated ptsAB (SEQ ID NO: 2), ptsC (SEQ ID NO: 4), ptsD (SEQ ID NO: 6), ptsE (SEQ ID NO: 8), ptsF (SEQ ID NO: 10) and ptsG (SEQ ID NO: 12), (encoding polypeptides SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ

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ID NO: 9, SEQ ID NO:11 and SEQ ID NO: 13, respectively) consisting essentially of the nucleotide sequence as shown in and SEQ ID NO: 1. Nucleic acid sequences complementary to all or a portion of the sequence described by SEQ ID NO: 1 and nucleic acid sequences which hybridize under stringent conditions to all or a portion of the sequence described by SEQ ID NO: 1 or its complement are also embraced by the present invention. Web site: http://www.delphion.com/details?pn=US05643747__ •

Genetic detoxification of pertussis toxin Inventor(s): Boux; Heather A. (Aurora, CA), Cockle; Stephen A. (Richmond Hill, CA), Klein; Michel H. (Willowdale, CA), Loosmore; Sheena M. (Aurora, CA), Zealey; Gavin R. (Concord, CA) Assignee(s): Connaught Laboratories Limited (Willowdale, CA) Patent Number: 5,221,618 Date filed: September 30, 1991 Abstract: A new method is described for the preparation of a safe, immunogenic and efficacious vaccine for protection against the disease pertussis. In development of this vaccine, specific functional sites of pertussis toxin have been identified, and using this information, defined mutant holotoxins have been produced by site directed mutagenesis of the toxin gene. A number of these toxin analogues are detoxified, retain an immunodominant S1 epitope, are immunogenic and are protective in the standard pertussis vaccine potency test in mice. Excerpt(s): The present invention relates to a novel method for the detoxification of pertussis toxin by the genetic manipulation of DNA segments coding for one or more amino acid residues essential for the toxin's biological activity. It also relates to a procedure for the creation of genetically altered Bordetella pertussis bacteria that produce the said detoxified pertussis toxin. Whooping cough, or pertussis, is a severe, highly contagious respiratory disease of infants and young children caused by infection with Bordetella pertussis. Owing to the many virulence factors associated with this organism, the pathogenesis of the disease is still not fully understood; however, it is generally recognized that the major systemic effects are caused by pertussis toxin (PT). This material exhibits a wide range of biological activities as illustrated by such alternative names as lymphocytosis-promoting factor, histamine-sensitizing factor and islet-activating protein. Many of these effects are associated with its biochemical function as an adenosine diphosphate (ADP)-ribosyltransferase. ADP- ribosylation of certain acceptor guanosine triphosphate-binding proteins leads to a loss of control over a variety of metabolic pathways mediated by cyclic adenosine monophosphate and by phospholipase C. In the absence of a protein acceptor, PT also catalyses the hydrolysis of nicotinamide adenine dinucleotide (AND glycohydrolase activity). Conventional killed whole-cell pertussis vaccines contain a mixture of antigens and there has been a great deal of work towards the development of a defined acellular vaccine comprising specific protective antigens. PT is the most significant protective antigen. Other antigens under consideration are agglutinogens and filamentous hemagglutinin (FHA). Web site: http://www.delphion.com/details?pn=US05221618__

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Manipulation of gene copy number in bordetella Inventor(s): Klein; Michel (16 Munro Boulevard, Willowdale, Ontario, CA), Loosmore; Sheena (70 Crawford Rose Drive, Aurora, Ontario, CA), Yacoob; Reza (2354 Old Pheasant Road, Mississauga, Ontario, CA), Zealey; Gavin (348 Charlton Avenue, Thornhill, Ontario, CA) Assignee(s): none reported Patent Number: 5,849,530 Date filed: May 4, 1995 Abstract: A protein expression levels from Bordetella strains, particularly Bordetella pertussis, are altered by genetic modification to a natural Bordetella strain whereby one or more of the natural genes, particularly including the TOX, FHA, CYA and PRN genes, is deleted from the genome of the natural strain and one or more of the natural genes or a genetic mutation thereof, particularly a genetically-detoxified TOX* gene, or a hybrid gene, is inserted into the genome of the natural strain to provide at least two copies of one or more of the natural genes or genetic mutation thereof or hybrid gene, singly or in tandem. The altered genotype Bordetella strain is useful in producing whole-cell or defined component vaccines against Bordetella, particularly whooping cough, which may be employed in combination with other vaccines. Excerpt(s): The present invention relates to a novel approach to alter gene expression in Bordetella species by manipulation of gene copy number. Whooping cough in humans is caused by members of the Bordetella species, especially B. pertussis. Following disease or vaccination, antibodies are elicited against several bacterial proteins, especially pertussis toxin (PT), filamentous haemagglutinin (FHA), the 69kDa outer membrane protein (69kD or pertactin) and the fimbrial agglutinogens. PT is a major protective antigen and is also associated with virulence. These antigens have been proposed to formulate single or multi-component pertussis vaccines and, as such, their efficient production and purification are essential. During fermentation of B. Pertussis, it has been found that FHA is secreted at 7 and 10 times the molar levels of 69kD or PT, respectively. Therefore, PT and pertactin are limiting antigens in the production of a component vaccine. Furthermore, the relative overproduction of FHA makes the purification of other antigens expressed at lower levels more difficult. This is especially true for PT, which may be initially co-purified with FHA in some purification protocols. It is also of concern that active PT may contaminate the FHA preparation, which then needs to be chemically detoxified to inactivate the residual native toxin. In the case of genetically detoxified pertussis toxin (described in published EPO patent application No. 0322115 and corresponding U.S. Pat. No. 5,085,862, assigned to the assignee hereof and the disclosure of which is incorporated herein by reference; Loosmore et al., Infect. Immun. 58, 3653 ›1990!), this would not be a problem. In either case, it would be advantageous, from a vaccine production viewpoint, to have a B. pertussis strain which does not produce FHA and/or one which does not produce PT. For example, an FHA.sup.- strain in which the FHA gene has been deleted could be used to produce all other antigens under optimized fermentation and purification conditions. Similarly, a PT.sup.- strain would produce FHA with no possibility of contamination by pertussis toxin. Web site: http://www.delphion.com/details?pn=US05849530__

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Method for isolating and purifying bordetella pertussis antigenic factors Inventor(s): Capiau; Carine (Harveng Mons, BE), Desmons; Pierre (Nivelles, BE) Assignee(s): SmithKline Beecham Biologicals (Rixensart, BE) Patent Number: 5,391,715 Date filed: March 24, 1992 Abstract: A process is provided for the purification of pertussis toxin (PT) and/or filamentous hemagglutinin antigen (FHA) from a B. pertussis fermentation broth or cell free culture supernatant containing at least one antigen, which comprises contacting the fermenation broth or cell free culture supernatant with a hydroxyapatite adsorbent for a sufficient time to adsorb the antigen(s) at a pH which both PT and FHA are adsorbed and eluting a mixture containing the adsorbed antigen(s) from the adsorbent with eluant at a pH which both PT and FHA are eluted. The PT and FHA may be further purified by two sequential chromatographic columns, one of which involves apolarligand chromatography. Excerpt(s): The present invention relates generally to components for a vaccine against whooping cough. More specifically, the invention provides a process for isolating and purifying antigenic factors from Bordetella pertussis in high yield and in a pure and stable form, the purified factors and mixtures thereof. Whooping Cough, or pertussis, is a highly infectious disease which primarily affects children. In addition to causing respiratory complications, whooping cough may result in nerve damage and high mortality, particularly in children in low socioeconomic groups and in newborn infants without maternal anti-pertussis antibodies. The etiologic agent of pertussis is the gram negative coccobacillus Bordetella pertussis. The bacteria is believed to invade the respiratory tract and induce a toxic state which remains even after the disappearance of the bacteria. Although world health organizations presently recommend the immunization of infants to prevent the incidence and spread of pertussis, great concern has arisen over the negative effects of various vaccine forms. The toxicity of conventional B. pertussis vaccine formulations causes side effects which vary from simple flushing to permanent neurological damage and/or death. Consequently, reduced use of conventional B. pertussis vaccines has resulted in an increase in the number of pertussis cases. Web site: http://www.delphion.com/details?pn=US05391715__

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Method for the treatment of pertussis with aminoguanidine Inventor(s): Goldman; William E. (St. Louis, MO) Assignee(s): Washington University (St Louis, MO) Patent Number: 5,317,040 Date filed: January 26, 1993 Abstract: A method for the treatment of pertussis is disclosed which comprises administering a selective inhibitor of inducible nitric oxide synthase, preferably aminoguanidine, to a mammalian host susceptible to pertussis in a small but effective amount for inhibiting the toxic effects of TCT released by Bordetella pertussis. Excerpt(s): The present invention relates to a method for the treatment of pertussis. Despite the availability of a highly effective vaccine, whooping cough (pertussis) remains a global problem and a persistent clinical challenge. Fears about vaccine safety

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have spawned recent epidemics in industrialized nations like Japan, Great Britain, and Sweden; even in the U.S., with vaccine acceptance approaching 95%, new estimates of the annual number of pertussis cases are as high as 125,000 (Sutter et al., JAMA 26-7, 386-391 (1992).]Much of pertussis research has centered on the development of an acellular vaccine with a lower side effect rate, but it is unlikely that the pertussis burden in well-vaccinated countries will decrease. Infants and children hospitalized with pertussis still must endure frequent violent coughing episodes that continue for weeks after antibiotics have eliminated the bacteria. Complications range from the encephalopathy (presumably from anoxia) to secondary pneumonia, the latter being the most frequent cause of pertussis-related mortality [Olson, Medicine 54, 427-469 (1975)]. Currently, there is no therapy to relieve the debilitating symptoms of pertussis, shorten its duration, or reduce the frequency of sequelae. The causative agent of pertussis is Bordetella pertussis (and, less frequently, B. parapertussis), which specifically colonizes and then destroys the ciliated cells lining the large airways [Mallory et al., J. Med. Res. 27, 115-123 (1912)]. The consequences of this cytopathology are severe, since ciliary activity is normally the sole means of transporting mucus out of the respiratory tract. As mucus, multiplying bacteria, and inflammatory debris accumulate, coughing becomes the only remaining means of airway clearance. Web site: http://www.delphion.com/details?pn=US05317040__ •

Modification of pertussis toxin Inventor(s): Armstrong; Glen D. (Edmonton, CA), Cockle; Stephen A. (Richmond Hill, CA), Hazes; Bart (Edmonton, CA), Klein; Michel H. (Willowdale, CA), Loosmore; Sheena (Aurora, CA), Oomen; Raymond P. (Tottenham, CA), Read; Randy J. (Edmonton, CA), Stein; Penelope E. (Edmonton, CA) Assignee(s): University of Alberta (Edmonton, CA) Patent Number: 5,856,122 Date filed: August 22, 1994 Abstract: The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin. Excerpt(s): The present invention relates to a method for the prediction of functional amino acid residues in pertussis toxin, in order to manipulate the biological properties of the toxin, by determination of and examination of the crystal structures of the toxin alone and of complexes of the toxin with molecules relevant to its biological activity, including carbohydrate ligands, nucleotide effectors and substrates. Whooping cough, or pertussis, is a severe, highly contagious respiratory disease of infants and young children caused by infection with Bordetella pertussis. Owing to the many virulence factors associated with this organism, the pathogenesis of the disease is still not fully understood; however, it is generally recognized that major systemic effects are caused by pertussis toxin (PT). This material exhibits a wide range of biological activities, as illustrated by such alternative names as lymphocytosis-promoting factor, histaminesensitizing factor and islet-activating protein (ref. 1- a list of the references appears at the

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end of the disclosure, each of which reference is incorporated herein by reference thereto). The B oligomer mediates the binding of the holotoxin to target cells and facilitates entry of the A protomer. PT has lectin-like properties, binding to glycoconjugates on many cell surfaces and to the oligosaccharide moieties of many serum glycoproteins (refs. 6,7). It has been reported that the toxin preferentially recognizes asparagine-linked oligosaccharide chains containing (2.alpha.-6) -linked sialic acid residues (ref. 6). However, a number of complex carbohydrate sequences are bound, and there is evidence that PT contains at least two binding domains with different specificities on each of the subunits S2 and S3 (refs. 7,8). Web site: http://www.delphion.com/details?pn=US05856122__ •

Pertussis toxin and use in vaccines Inventor(s): Arico'; Maria B. (Quercegrossa, IT), Nicosia; Alfredo (Siena, IT), Rappuoli; Rino (Quercegrossa-Monteriggioni, IT) Assignee(s): Sclavo S.p.A. (Siena, IT) Patent Number: 5,427,788 Date filed: June 17, 1994 Abstract: Cloning and sequencing of the Eco RI fragment of B. pertussis chromosomal DNA with 4696 base pairs, containing the genes which code for the five subunits of the pertussis toxin.A hybrid plasmid containing the DNA fragment or its further fragments and a micro-organism transformed by the hybrid plasmid and capable of expressing the cloned DNA fragment or further fragments thereof by synthesis of the pertussis toxin or one or more subunits of the pertussis toxin.The pertussis toxin or one or more subunits of the pertussis toxin so obtained are useful for the preparation of vaccines and diagnostic kits. Excerpt(s): The present invention relates to a cloned and sequenced Eco RI fragment of Bordetella pertussis chromosomal DNA containing the genes which code for the five subunits of the pertussis toxin, useful for the preparation of the pertussis toxin or of one or more subunits of the pertussis toxin. The present invention also relates to a hybrid plasmid containing the cloned and sequenced DNA fragment or further fragments thereof and to a micro-organism transformed by the hybrid plasmid and capable of expressing the cloned DNA fragment or further fragments thereof by synthesis of the pertussis toxin or one or more subunits of the pertussis toxin. The invention also concerns a method for the preparation of the pertussis toxin or one or more subunits of the pertussis toxin which includes the growth of the micro-organism transformed by the hybrid plasmid in a suitable culture medium. Web site: http://www.delphion.com/details?pn=US05427788__

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Pertussis toxin induced lymphocytosis Inventor(s): Pauza, Jr.; C. David (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 5,888,726 Date filed: April 23, 1997

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Abstract: The present invention involves HIV evaluation and AIDS treatment by eliciting lymphocytosis with pertussis toxin in order to reveal the sequestered HIV or SIV in the lymph tissues enabling HIV infection analysis, viral quantification and treatment. The lymphocytosis itself causes an alleviation of the AIDS symptoms and a reduction in the viral load. The present invention could also be used in conjunction with a large variety of adjunct therapies. Excerpt(s): Acquired Immune Deficiency Syndrome, or AIDS, causes an immunosuppression of certain cells critical to eliciting an immune response. AIDS is caused by the Human Immunodeficiency Virus or HIV. Specifically, three outbreaks of primate lentiviruses have been recognized: HIV-1 in central Africa, Asia, North America and Europe; HIV-2 in West Africa; Simian Immunodeficiency Virus (SIV) in captive and wild nonhuman primate populations. Comparative analysis between HIV-1 and HIV-2 nucleotide sequences show little homology, only 42%. Conversely, HIV-2 is closely related to SIV. The lymph node is a microcosm of HIV and SIV infection that highlights the competition between virus destruction and virus replication because both of these processes require T lymphocyte activation. T lymphocytes are included in the category of white blood cells and are produced in spleen, thymus, and bone marrow. They are essential elements in all immune reactions by virtue of their key regulatory functions. Another population of immune cells are termed macrophages: they are also involved in several immune functions and are considered essential. Specific subpopulations of T lymphocytes and macrophages present the CD4 molecule on their cell surface. This molecule binds HIV-1 to these cells and facilitates their destruction. The level of circulating T lymphocytes in AIDS patients is depressed and this is especially evident for the T helper cell subset. Whereas the ratio of T.sub.H to T.sub.S (T suppressor cells) cells in normal humans averages 2.3, the T.sub.H /T.sub.S ratio in AIDS patients is less than 0.9. Web site: http://www.delphion.com/details?pn=US05888726__ •

Pertussis toxin used as a carrier protein with non-charged saccharides in conjugate vaccines Inventor(s): Levi; Lily (Haifa, IL), Robbins; John B. (Chevy Chase, MD), Schneerson; Rachel (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,445,817 Date filed: August 21, 1992 Abstract: A medically important and useful conjugate comprising pertussis toxin (PT), or another antigen having similar physico-chemical properties, as the carrier protein component, coupled to a neutral or non-charged saccharide, particularly, the capsular polysaccharide of Streptococcus pneumoniae type 14 (Pn14), for use as an effective, nontoxic, and highly immunogenic vaccine is described. The invention is directed to a novel synthetic scheme wherein PT and like proteins, and a derivative of Pn14, and the like, were coupled at acidic pH via carbodiimide-mediated condensation to produce an immunogenic conjugate. The coupling procedure yielded a Pn14-PT conjugate in which the PT component was rendered non-toxic and both the PT and Pn14 components were immunogenic, as determined by the production of protective levels of both type-specific and neutralizing antibodies in mammals. The Pn14-PT conjugate was used as an

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immunogen at levels estimated to be protective in humans and stands to provide an effective, safe, and potent human vaccine. Excerpt(s): The present invention relates to the production of clinically acceptable carrier protein-saccharide (e.g. polysaccharide and oligosaccharide) conjugates which are useful as effective vaccines, especially in infants and young children, for the induction of protective levels of antibodies against medically important pathogens, particularly, for example, the capsular polysaccharide of Streptococcus pneumoniae type 14 (hereinafter also referred to as pneumococcus type 14 or Pn14), and pertussis toxin (hereinafter also referred to as PT) produced by the Bordetella pertussis bacterium. The development of safe and effective vaccines is essential to prevent systemic infections, which continue to cause high rates of morbidity and mortality throughout the world. To prevent and ultimately eradicate a wide variety of systemic infections caused by bacterial pathogens or microorganisms with neutral polysaccharides, universal immunization of infants and adults with suitable vaccines, which are capable of eliciting safe, effective, and longlasting immunity, is needed. Because the incidence of diseases caused by invasive bacterial pathogens is highest in children under two years of age, effective immunization must begin early and optimally be completed within the first half year of life. Subsequent booster immunizations at about fifteen months and five years may also be advocated. Surface polysaccharides serve as essential virulence factors and protective antigens for invasive bacteria which infect the bloodstream as their primary pathogenic event (39, 41). These surface antigens include capsular polysaccharides of both Gramnegative and Gram-positive bacteria and the lipopolysaccharides of Gram-negative bacteria. Although most of these purified polysaccharides elicit protective levels of antibodies in healthy adults, both capsular polysaccharides and lipopolysaccharides have immunologic properties or pharmacologic activities that limit their use as vaccines. Capsular polysaccharides are known in the medical literature and are polymers of sugars, sugar acids, amino sugars, polyhydric alcohols, and sugar phosphates. The capsular polymers may contain linkages other than glycosidic linkages and constituents other than the abovementioned sugars. Web site: http://www.delphion.com/details?pn=US05445817__ •

Pertussis toxoid made by reacting pertussis toxin with the nitrating agent TNM Inventor(s): Winberry; Larry K. (Brockton, MA) Assignee(s): Massachusetts Health and Research Institute (Boston, MA) Patent Number: 5,989,564 Date filed: September 12, 1991 Abstract: A toxoid of pertussis toxin in which the pertussis toxin is modified essentially only at one or more tyrosine residues, as by the use of a nitrating agent such as tetranitromethane or by recombinant DNA techniques; a vaccine including the toxoid; and methods of preparing the toxoid and the vaccine. Excerpt(s): This invention relates to the development of antigens suitable as vaccines for preventing whooping-cough. Whooping-cough is a severe, highly contagious respiratory disease resulting from infection with the bacterium Bordetella pertussis. At the present time there is no fully effective treatment, the disease is associated with substantial morbidity and mortality, and is widespread throughout the world. Whooping-cough is particularly severe in infants. Pertussis vaccine composed of killed cells has been playing a role in the reduction of whooping cough for more than 40 years

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throughout the world. At the same time, however, it is one of the most rejected of vaccines because of its adverse reactions. It is now time that the whole-cell vaccine be replaced by a more defined vaccine that is composed of specific components and is able to have its protective potency evaluated by means of purified reference protective antigens or antibodies. In Japan, a pertussis vaccine in use since 1981 has had some adverse effects reduced by removal of the endotoxin from a fraction of culture supernatant of Bordetella pertussis phase I cells and inactivation of some of the toxicity with Formalin. The main components of the vaccine are formalinized pertussis toxin (PT) and filamentous hemagglutinin (FHA). Now we understand that PT is the most potent antigen and FHA is a helpful protective antigen and that their antibodies play an important role in protecting mice from infection and disease caused by the pathogen. Web site: http://www.delphion.com/details?pn=US05989564__ •

Pharmaceutical compositions for the treatment of autoimmune diseases comprising the B-oligomer of pertussis toxin or its subunits Inventor(s): Ben-Nun; Avraham (Yavne, IL) Assignee(s): Yeda Research and Development Co. Ltd. (Rehovot, IL) Patent Number: 5,858,965 Date filed: July 30, 1997 Abstract: The invention provides the use of a protein selected from the B-oligomer of pertussis toxin, an individual subunit S2, S3, S4 or S5 thereof, or a combination of the subunits, for the preparation of pharmaceutical compositions comprising them for the treatment of autoimmune diseases. Excerpt(s): The present invention is generally in the field of agents that may be used for the treatment of autoimmune diseases, and more particularly relates to pharmaceutical compositions comprising the B-oligomer of pertussis toxin or one of its subunits S2, S3, S4 or S5, or combinations thereof, useful for protection against autoimmune diseases. The gram-negative bacterium Bordetella pertussis (B. pertussis), the causative agent of whooping cough, produces several virulence factors. Pertussis toxin (PT), the major virulence component of B. pertussis, appears to contain an important epitope that leads to the formation of antibodies capable of protecting against the disease. Therefore, PT has been extensively investigated with regard to its possible use in preparing vaccines for whooping cough (Black et al., 1988). Pertussis toxin is a 105-kDa hexameric protein composed of five distinct non-covalently linked polypeprides designated (in the order of decreasing molecular weight) S1-S5.PT can be divided into two distinct functional units, the enzymatically active toxic A-protomer, consisting of a single polypeptide (S1), and the pentameric B-oligomer (S2, S3, two copies of S4, and S5, i.e. molar ratiol:1:2:1). The B-oligomer is responsible for binding of the toxin to the surface of eukaryotic target cells. The two S4 polypeptides form two distinct heterodimers with S2 and S3, which are in turn held together by S5 (see review by Gierschik, 1992). Web site: http://www.delphion.com/details?pn=US05858965__

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Polypeptide compound which binds to glyco-conjugates and to artificial pertussis toxin antigen Inventor(s): Bartfai; Tamas (Stocksund, SE) Assignee(s): Trion Forskning-och Utvecklings Aktiebolag (Sollentuna, SE) Patent Number: 5,283,321 Date filed: July 18, 1989 Abstract: A polypeptide of the formulaH--X.sup.1 --Gln--Thr--Art--Ala--Asn--Pro--Asn-Pro--Tyr--Thr----Ser--Arg--Arg--Ser-- Val--Ala--Ser--X.sup.2 --Yin which X.sup.1 and X.sup.2 each represents an optional coupling-facilitating amino acid residue, and Y represents --OH or --NH.sub.2, and an artificial compound in free or carrier-associated form with the capability of binding to glyco-conjugates, especially immunoglobulins, which compound is chosen from the group consisting of said peptide and functional analogues and functional derivatives thereof, are disclosed. Additionally, there is described an artificial pertussis toxin antigen, which mainly consists of at least one peptide sequence reacting with antibodies induced by the native pertussis toxin selected from the above polypeptide and parts thereof. The above described artificial pertussis toxin antigen is included as a diagnostic antigen in a diagnostic immunoassay kit for the determination of antibodies induced by the native pertussis toxin in a sample of biological fluid, and as an immunizing component in a vaccine composition against whooping cough, respectively. Furthermore, there is described an intradermal skin test composition comprising the above described artificial pertussis toxin antigen. Excerpt(s): The present invention relates to a new polypeptide, to an artificial compound, selected from the new peptide and functional analogues and derivatives of the peptide, in free or carrier-associated form with the capability of bindning to glycoconjugates, especially immunoglobulins, to artificial pertussis toxin antigens, which mainly consist of peptide sequences reacting with antibodies induced by the native pertussis toxin selected from the new polypeptide and parts thereof, to a diagnostic immunoassay kit comprising as a diagnostic antigen, said antigens reacting with antibodies induced by the native pertussis toxin, to a vaccine composition comprising as an immunizing component antigens selected from said antigens reacting with antibodies induced by the native pertussis toxin, and to an intradermal skin test composition comprising antigens selected from said antigens reacting with antibodies induced by the native pertussis toxin. In the field of immunology it is well known that most biological organisms produce specific proteins which selectively and specifically recognize various protein and/or carbohydrate structures. Examples of such specific proteins derived from bacteria are Protein A and Protein G which both bind to certain immunoglobulins from various species. Examples of such specific proteins derived from plants or lower invertebrates are so-called lectins which bind to carbohydrate structures of immunoglobulins and other glyco-conjugates. Examples of such lectins are Concanavalin A, Wheat germ agglutinin, Phytohaemagglutinin and Helix pomatia lectin. Each of the above mentioned specific proteins bind to a specific group of protein structures and/or carbohydrate structures. Web site: http://www.delphion.com/details?pn=US05283321__

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Process for purification of a 69000 dalton antigenic protein from Bordetella pertussis Inventor(s): Gotto; John W. (Suffern, NY) Assignee(s): American Cyanamid Company (Wayne, NJ) Patent Number: 5,276,142 Date filed: December 11, 1989 Abstract: A process for extracting and purifying a protein having an apparent molecular weight of about 69,000 daltons from the outer membrane of the bacterium Bordetella pertussis is provided. The process includes inactivating Bordetella pertussis cells with a bacteriostatic agent, repetitive extraction, and purification of the 69,000 dalton protein from extract by dye ligand chromatography followed by chromatofocusing. The process results in improved yield and stability of the 69,000 dalton protein. Excerpt(s): The invention relates to a process for extracting and purifying a protein having an apparent molecular weight of about 69,000 daltons from the outer membrane of the bacterium Bordetella pertussis. The protein so extracted and purified may be utilized as a component of an acellular pertussis vaccine. The bacterium Bordetella pertussis is the causative agent of the serious infectious disease known as pertussis or whooping cough. Vaccines which are used to immunize infants and children are composed of whole cells of B. pertussis inactivated with chemical agents or heat. While whole cell vaccines contain the antigenic components necessary to elicit protective immunity, they may also contain substances irrelevant to protection and possibly related to undesirable side effects of immunization. In order to employ the 69K protein as a component of an acellular pertussis vaccine, a method is required for the efficient purification of the protein applicable to commercial production scale. Previously described methods, however, have several disadvantages for adaptation to large scale. Web site: http://www.delphion.com/details?pn=US05276142__

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Production of bordetella pertussis toxin with a low concentration of iron Inventor(s): Sekura; Ronald D. (Rockville, MD), Shiloach; Joseph (Rockville, MD), Zhang; Yan-Ling (Rockville, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,338,670 Date filed: December 11, 1992 Abstract: A fermentation level cultivation of Bordetella pertussis bacteria on commercial scale is described. The critical factors in large scale cultivation of the bacteria are the presence of an antifoam agent and maintaining proper oxygen level and iron content in the culture medium. Pertussis toxin produced by the bacteria parallels the rate of growth of the bacteria. Excerpt(s): The present invention is related to a method of culturing Bordetella pertussis (B. pertussis) on a large scale. More particularly, the present invention is related to a method of fermentation level cultivation of B. pertussis concurrently producing pertussis toxin. Pertussis toxin is one of the various components produced by virulent B. pertussis, the microorganism that causes whooping cough. This toxin is a major protective antigen against whooping cough. Other components of interest produced by B. pertussis are filamentous hemagglutinin, heat labile toxin, adenylate cyclase and the

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like which may also play important role as protective antigens. Large scale production of these components which are useful as diagnostic or chemical reagents and in the preparation of vaccines requires large scale cultivation of the microorganism. Bordetella pertussis is a fastidious organism which has proved difficult to grow in large fermentors. Current methods for the culture of B. pertussis employ cultivation in stationary culture or in fermentors. Growth in stationary culture is labor intensive while cultivation on a fermentation scale requires vortex stirring and surface aeration. As a result, the effective volume of the fermentor is reduced and modification of the fermentor for growth of pertussis is often necessary, for example the baffles must be removed. Furthermore, the quantities of pertussis toxin produced during fermentation under these conditions are variable and often low. Web site: http://www.delphion.com/details?pn=US05338670__ •

Promoter of the gene which codes for the pilinic subunit fim3 of Bordetella pertussis and its use for the expression in Bordetella of the genes which code for a protein of interest Inventor(s): Cuzzoni; Anna (Pavia, IT), de Ferra; Francesca (San Donato Milanese, IT), Grandi; Guido (Segrate - San Felice, IT), Pedroni; Paola (Milan, IT), Riboli; Barbara (Cremona, IT) Assignee(s): Eniricerhce S.p.A. (Milan, IT) Patent Number: 5,395,764 Date filed: March 16, 1994 Abstract: The isolation and characterization of the promoter regions of the genes which code for the pilinic subunits fim2, fim3 and fimx of Bordetella pertussis, are described, as well as the construction of vectors containing the regions, and microorganisms transformed by the vectors.The promoter regions, or nucleotide fragments thereof, are particularly useful for the regulable or non-regulable expression of genes which code for a protein of interest in a strain of Bordetella. The transformed Bordetella strains are particularly suitable for the development of an effective anti-pertussis vaccine. Excerpt(s): The present invention relates in general to the isolation and characterisation of the promoter regions of the genes which code for the pilinic subunits fim2, fim3 and fimx of Bordetella pertussis, vectors containing the regions, microorganisms transformed by the vectors, and the use thereof for the expression of genes which code for a protein of interest. In particular, the present invention relates to the use of the promoter regions or nucleotide fragments thereof for the regulated or non-regulated expression of genes which code for a protein of interest in a strain of Bordetella and the use of that strain for the development of an effective anti-pertussis vaccine. Bordetella pertussis (B. pertussis) is the etiological agent of pertussis, a disease of the respiratory tract which is transmitted from a sick person to a susceptible healthy individual during the virulent stage. Web site: http://www.delphion.com/details?pn=US05395764__

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Vaccine Inventor(s): Lobet; Yves (Rixensart, BE), Locht; Camille (Wannehain, FR) Assignee(s): SmithKline Beecham Biologicals (S.A.) (Rixensart, BE) Patent Number: 5,786,189 Date filed: December 11, 1996 Abstract: The Bordetella pertussis toxin is genetically modified to express a toxin protein which is deficient in target-cell receptor binding and is used in a vaccine for protection against whooping cough. Excerpt(s): This invention relates to genetic modifications of the Bordetella pertussis toxin and to a vaccine comprising an immunoprotective amount of such protein. The members of the genus Bordetella are pathogenic microorganisms involved in the infection of the respiratory tract. The genus is comprised of four species; B. pertussis, B. parapertussis, B. bronchiseptica, and B. avium. The most virulent species to man is B. pertussis, which is the etiologic agent of whooping cough. Current conventional pertussis vaccines contain whole but inactivated B. pertussis cells. Such cells are inactivated by treatment at 56.degree. C. for 30 minutes and/or treatment with formaldehyde. In spite of inactivation, such whole cell vaccines retain a substantial amount of toxicity. Web site: http://www.delphion.com/details?pn=US05786189__

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Whooping cough vaccine comprising a fimbria protein Inventor(s): Mooi; Frederik Robert (Utrecht, NL) Assignee(s): De Staat der Nerderlanden Vertegenwoordigd Door de Minister Van Welzijn, (Rijswijk, NL) Patent Number: 5,798,103 Date filed: January 8, 1993 Abstract: The invention relates to acellular vaccines being effective against whooping cough and is based on a functional component of the fimbriae of Bordetella pertussis i.e. the actual adhesin molecule being a "minor" component in the fimbriae. The vaccines according to the invention have the advantage that both they may induce an effective immune respons against all B. pertussis strains and--most likely--also against Bordetella paratertussis being the second important causative agent of whooping cough. Further, the vaccines may also be used for veterinary applications, to protect against Bordetella bronchiseptica infections. Excerpt(s): The invention relates to a whooping cough vaccine. Whooping cough or pertussis is caused by two closely related bacteria, Bordetella pertussis and Bordetella parapertussis ›Preston N. W. (1988). Pertussis Today. In:Pathogenesis and Immunity in Pertussis (Eds. Wardlaw A. C., and Parton R.). John Wiley and Sons, 1-18!. B. pertussis is most frequently isolated from whooping cough patients (in 70 to 97% of the cases), so most research is focused on this organism. B. pertussis attaches to the ciliated cells of the respiratory tract, where it proliferates and produces a number of toxins. Locally, the infection results in destruction of the ciliated cells, which can result in obstruction of the respiratory tract, paroxysmal cough, apnoea and encephalopathy, sometimes accompanied by fever. Whooping cough can occur in any age group, however, morbidity is highest in the age group below 2 years. Although B. pertussis is sensitive

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for a number of antibiotics, treatment with antibiotics is generally not effective after whooping cough has been diagnosed, presumably because toxins produced by the bacteria have already damaged the respiratory tract. Thus prevention of whooping cough by means of vaccination is highly desirable. Web site: http://www.delphion.com/details?pn=US05798103__

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

Acellular pertussis vaccine with diphthriae-and tetanus-toxoids Inventor(s): Florent, Patrick; (Brussels, BE), Stephenne, Jean; (Rixensart, BE), Vandecasserie, Christian; (Lasne, BE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20010014331 Date filed: April 6, 2001 Abstract: This invention relates to a diphtheria, tetanus and pertussis vaccine comprising a low dose of each of diphtheria toxoid (D), tetanus toxoid (T), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (69K). The vaccine maintains an ability to prevent pertussis while showing exceptionally low reactogenicity. Combination vaccines comprising additional antigens are also provided. Excerpt(s): The present invention relates to new vaccine formulations, comprising a low dose of the 69 kda outer membrane protein of Bordetella pertussis (hereinafter termed `69 K` or `69 K antigen` or pertactin, disclosed in European Patent 0 162 639. Recombinant 69 K (P69) has been described by N F Fairweather et al, Symposium On Pertussis (Bethesda), Sep. 26-28 1990). The invention in particular relates to a vaccine comprising more than one antigen, especially a multivalent vaccine, that is: a vaccine for the amelioration or treatment of more than one disease state, in which a low dose of 69 K is present. The present invention also relates to the production and use of such vaccines in medicine. It is known that 69 K is an important component of acellular pertussis vaccines (Pa vaccines) for the effective prevention of pertussis. A study on the dose responses of 5 acellular pertussis vaccines in healthy adults was published by the US National Institutes of Health (NIH) in May 1996 by Keitel, W. et al. 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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Acellular Pertussis Vaccines and Methods of Preparation Thereof Inventor(S): Barreto, Luis; (Ontario, Ca), Boux, Leslie; (Quebec, Ca), Fahim, Raafat E F; (Ontario, Ca), Herbert, Andrew; (East York, Ca), Jackson, Gail E D; (Ontario, Ca), Klein, Michel H; (Ontario, Ca), Tan, Larry U L; (Ontario, Ca), Thipphawong, John; (Mountain View, Ca), Vose, John R; (Tassin La Demi-Lune, Fr) Correspondence: Michael I Stewart; Sim & Mcburney; 330 University Avenue; 6th Floor; Ontario; M5g1r7; CA Patent Application Number: 20010009666 Date filed: June 9, 1998 Abstract: Acellular pertussis vaccines comprise purified toxin or toxoid thereof, filamentous haemagglutinin, pertactin and fimbrial agglutinogens formulated to confer protection to at least 70% of members of an at-risk population. The fimbrial agglutinogens may be prepared from a Bordetella strain, particularly a B. pertussis strain, by a multiple step procedure involving extraction of the fimbrial agglutinogens from cell paste and concentrating and purifying the extracted material. Excerpt(s): This application is a continuation-in-part of copending U.S. patent application Ser. No. 08/501,743 filed Jul. 12, 1995, which itself is a continuation-in-part of copending U.S. patent application Ser. No. 08/433,646 filed May 4, 1995. The present invention relates to acellular pertussis vaccines, components thereof, and their preparation. Whooping cough or pertussis is a severe, highly contagious upper respiratory tract infection caused by Bordetella pertussis. The World Health Organization estimates that there are 60 million cases of pertussis per year and 0.5 to 1 million associated deaths (ref. 1. Throughout this specification., various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately following the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure) In unvaccinated populations, a pertussis incidence rate as high as 80% has been observed in children under 5 years old (ref. 2). Although pertussis is generally considered to be a childhood disease, there is increasing evidence of clinical and asymptomatic disease in adolescents and adults (refs. 3, 4 and 5). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Antigenic preparations and the isolation of such preparations Inventor(s): Crespo, Juan Antonio Montaraz; (Naucalpan, Mx), Ivanyi, Juraj; (London, Gb), Novotny, Jaroslava; (Kent, Gb), Novotny, Pavel; (Residence, Xp) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020150595 Date filed: June 30, 1999 Abstract: The present invention provides novel antigenic preparations comprising proteinaceous material associated with adenylate cyclase activity in cultures of B.pertussis, the said preparations being useful as components of acellular whooping cough vaccines. The invention further provides methods for the isolation of such antigenic preparations.

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Excerpt(s): The present invention relates to antigenic preparations for use in acellular vaccines against Bordetella pertussis, and to a method for the isolation of such preparations. Bordetella pertussis causes a serious and debilitating disease in humans, children being particularly susceptible, which is kept under control in the developed countries by large scale immunisation programmes. It has been found that immunisation is a very important factor in the reduction of the disease and that failure to vaccinate can lead to increased incidence of the disease. In practically all areas, immunisation is effected using a whole cell B. pertussis vaccine which has been found to be relatively effective in preventing the disease. However, it has been recognised that whole cell vaccines may suffer from several draw-backs. Thus, for example, in about 1 in every 10,000 children inoculated, clinical symptoms occur which may include fever, local reactions and persistent screaming. Further, it would appear that some batches of whole cell vaccine provide no protection at all while still being associated with the possibility of undesirable side-effects. With the currently low occurrence of the disease in developed countries with immunisation programmes, the benefit/risk ratio is poorly defined, and many clinicians believe that the risks of inoculation outweigh the benefits gained by immunisation. As a result, many children are not inoculated and there is then a serious risk of a pandemic of whooping cough. Considerable research effort has, therefore, been directed towards the development of improved pertussis vaccines and especially acellular vaccines which lack the components associated with the toxic effects of the whole cell vaccines hitherto used whilst incorporating those components necessary to protect against the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anti-Viral Treatment With Pertussis Toxin B Oligomer Inventor(s): Alfano, Massimo; (Floral Park, NY), Bukrinsky, MIchael; (Glenwood Landing, NY) Correspondence: Piper Marbury Rudnick & Wolfe Llp; Steven B Kelber; 1200 Nineteenth Street, NW; Washington; DC; 20036-2412; US Patent Application Number: 20020172687 Date filed: January 31, 2000 Abstract: There is disclosed a method for anti-viral therapy, and for decreasing infectivity of viruses that use the chemokine CCR5 receptor as a co-receptor by treatment with the B. pertussis toxin (PTX) B oligomer, wherein the PTX B oligomer is composed of from two to ten subunits of PTX B oligomer selected from the group consisting of S2, S3, S4, S5, and combinations thereof. Excerpt(s): This application is a continuation-in-part of, and claims priority from, U.S. patent application Ser. No. 08/911,879, filed Aug. 15, 1997. The present invention provides methods for anti-viral infection prevention and therapy, and for desensitizing the CCR5 chemokine receptor by treatment with the B. pertussis toxin (PTX) B oligomer. Viral infections are a continuing medical problem because, like any rapidly-dividing infectious agent, there are continuing mutations that help some sub-populations of viruses resistant to current treatment regimens. Many virally-based diseases do not have effective anti-viral treatments, because such treatments address the symptoms of the viral disease and not the root cause of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Heterocycle derivatives and methods of use Inventor(s): Gessell-Lee, Deborah L.; (Galveston, TX), Peterson, Johnny W.; (Dickinson, TX), Saini, Shamsher S.; (Dickinson, TX) Correspondence: Mueting, Raasch & Gebhardt, P.A.; P.O. Box 581415; Minneapolis; MN; 55458; US Patent Application Number: 20020032228 Date filed: May 19, 2001 Abstract: The present invention provides methods for treating intestinal fluid loss, whooping cough, anthrax, and conditions associated with smooth muscle contraction. The present invention also provides methods for inhibiting adenylate cyclase in vivo and in vitro. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/210,412, filed Jun. 8, 2000, which is incorporated by reference herein. Diarrheal diseases in humans and non-human animals can be caused by several types of pathogens, including viruses, bacteria, parasites, and rotaviruses. The most prevalent are the bacteria Escherichia coli and Vibrio cholerea. Diarrheal diseases are a prevalent cause of morbidity and mortality in less developed countries. These diseases also afflict populations in developed countries. For example, each year in the US over 200,000 children 5 years and younger are hospitalized with acute diarrheal diseases. The infectious diarrheas are the leading cause of morbidity and mortality worldwide a common class of illness in the United States. Due to its many causes, acute infectious diarrhea can occur more than once in the same person, and, therefore, it is unlike most chronic conditions which typically occur once. Unlike other digestive diseases, infectious diarrheas are communicable via person-to-person contact or through contaminated food or water and can spread endemically or in epidemics through households, schools, day-care centers, nursing homes, and communities. Diarrheal diseases also pose a serious challenge in the raising of non-human animals in the farming industry, particularly with young calves and pigs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of separating protective components of bordetella pertussis Inventor(s): Fujii, Shigeo; (Yamaguchi, JP), Suehara, Akihiro; (Yamaguchi, JP), Yamamoto, Eiji; (Yamaguchi, JP) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030133941 Date filed: July 30, 2002 Abstract: To provide a method of efficiently separate protective components of Bordetella pertussisOn the basis of differences in adsorbability to calcium phosphate gel formed by adding calcium ions to a Bordetella pertussis culture in the presence of excess phosphate ions, protective components of Bordetella pertussis are separated from the Bordetella pertussis culture.Traditionally, protective components of Bordetella pertussis have been separated using different purification methods for the respective components. According to the present invention, the use of the same means of purification for all subject components makes it possible to purify each component with

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high efficiency and high recovery rate, an aspect very advantageous for industrial production. It is also possible to efficiently produce an improved purified pertussis component vaccine comprising an effective combination of pertussis filamentous hemagglutinin (FHA), pertactin (PRN, 69K-OMP), pertussis fimbriae (FIM) and pertussis toxin (PT). Excerpt(s): The present invention relates to a method of separating protective components of Bordetella pertussis. The pertussis component vaccine can be produced by suitably mixing the protective components separated by the method of the present invention. Vaccines are widely used to prevent communicable diseases. Pertussis, a communicable respiratory disease caused by infection with Bordetella pertussis, is likely to severely affect patients, especially infants, due to apneic cough with occasional spasm. To cope with this disease, it has been common practice to use whole cultured cells of Bordetella pertussis after inactivation (inactivated vaccine). However, localized reactions at the site of vaccination and side reactions, such as fever, have been reported, creating a social urge to solve this problem. To solve this problem, there have been a large number of attempts of using protective components separated from Bordetella pertussis as vaccine. For example, acellular pertussis vaccine (ACP vaccine), prepared by extracting protective proteins, such as pertussis toxin (PT), pertussis filamentous hemagglutinin (FHA), pertactin (PRN, 69K-OMP) and pertussis fimbriae (FIM), from Bordetella pertussis cells, and removing endotoxin (ET), is being into practical application, but is not fully satisfactory, due to the drawbacks described below. Pertussis toxin (PT), pertussis filamentous hemagglutinin (FHA), pertactin (PRN, 69KOMP) and pertussis fimbriae (FIM), all protective components of Bordetella pertussis already in practical application with validated efficacy, are separated by respective methods. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Peptides for the preparation of vaccines against bordetella pertussis and bordetella parapertussis Inventor(s): Mooi, Frederik Robert; (Wijk Bij Duurstede, NL) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20030187221 Date filed: April 10, 2003 Abstract: The present invention discloses polypeptides for use in vaccines against pertussis and parapertussis. The polypeptides of the invention are derived from the Bordetella pertussis pertactin. Preferably, the polypeptides of the invention comprise sequences from region 1 of pertactin, in particular they comprise one or more "GGFGP" or "GGAVP" repeats. Alternatively the polypeptides of the invention have a pertactin sequence from which part or all of region 1 or region 2 is deleted. The polypeptides of the invention are incorporated in compositions that are useful as vaccines for human and veterinary purposes. The invention further discloses antibodies against the pertactin-derived polypeptides of the invention. Excerpt(s): The present invention relates to peptides or polypeptides that can be used for pharmaceutical and/or veterinary purposes, and in particular in the preparation of vaccines against Bordetella pertussis and/or Bordetella parapertussis (henceforth collectively referred to as "Bordetella (para)pertussis".) The invention also relates to

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vaccines containing such peptides, and to the use of such peptides in the preparation of vaccines. The invention further relates to antibodies generated against these peptides, and to pharmaceutical compositions containing such antibodies. Conventionally, vaccines against pertussis ("whooping-cough") have been based on whole cells of B. pertussis. In recent years, besides these so-called "whole cell vaccines" or "WCV's", also vaccines have been developed that contain specific antigens derived from B. pertussis, such as fimbriae, filamentous hemagglutinin, pertussis toxin and/or a surfaceassociated protein of B. pertussis referred to as "pertactin". These so-called "acellular vaccines" or "ACVs" have now been introduced in several countries. The sequence of B. pertussis pertactin has been published (vide inter alia Charles et al., Proc. Natl. Acad. Sci. USA May 1989; 86(10): 3554-8 and SEQ ID NO: 6 below). Pertactin is a 69 kD protein comprising approximately 926 amino acid residues, which from X-ray data is known to form a helix with several protruding loops that contain sequence motifs associated with the biological activity of the protein (Emsley at al., Nature (1996) 381:90-92). These include a loop containing an Arg-Gly-Asp (RGD) tripeptide motif (amino acids 260-262) involved in adherence to host tissues and a loop with a (PQP).sub.5 motif near the carboxy- terminus containing the a major immunoprotective epitope (Charles et al., Eur. J. Immunol. (1991) 21:1147-1153.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pertussis toxin gene: cloning and expression of protective antigen Inventor(s): Cieplak, Witold; (Hamilton, MT) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 10154; US Patent Application Number: 20030044430 Date filed: February 23, 2001 Abstract: A cloned gene encoding the expression of an antigenic mutant pertussis toxin with substantially reduced enzymatic activity has been described. Excerpt(s): This is a continuation in part of the application Ser. No. 07/843,727 filed Mar. 25, 1986. The present invention is related to molecular cloning of pertussis toxin genes capable of expressing an antigen peptide having substantially reduced enzymatic activity while being protective against pertussis. More particularly, the present invention is related to bacterial plasmids pPTX42 and pPTXS1/6A encoding pertussis toxin. Pertussis toxin is one of the various toxic components produced by virulent Bordetella pertussis, the microorganism that causes whooping cough. A wide variety of biological activities such as histamine sensitization, insulin secretion, lymphocytosis promoting and immuno-potentiating effects can be attributed to this toxin. In addition to these activities, the toxin provides protection to mice when challenged intracerebrally or by aerosol. Pertussin toxin is, therefore, an important constituent in the vaccine against whooping cough and is included as a component in such vaccines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Polypeptides containing polymorphisms of the repeated regions of pertactin in bordetella pertussis, bordetella parapertussis, and bordetella bronchiseptica, their use in diagnostics, and in immunogenic compositions Inventor(s): Boursaux-Eude, Caroline; (Antony, FR), Guiso-Maclouf, Nicole; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20020192237 Date filed: September 10, 2001 Abstract: Pertactin (PRN) is an outer membrane protein expressed by Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica, which induces protective immunity to Bordetella infections. The immunodominant and immunoprotective epitopes of pertactin include two repeated regions, I and II. Comparison of these two repeated regions showed the pertactin of B. parapertussis is invariant, whereas the pertactin of B. pertussis varies mostly in region I and B. bronchiseptica varies in both the repeated regions I and II. Compositions containing pertactins and pertactin fragments containing variant sequences in these regions are useful as immunogenic compositions. Excerpt(s): This application is based on and claims the benefit of U.S. Provisional Application Ser. No. 60/206,969, filed May 25, 2000 (attorney docket no. 03495.6047) The entire disclosure of this application is relied upon and incorporated by reference herein. This invention relates to proteins and polypeptides of the Bordetella outer membrane protein called pertactin and the polynucleotides that encode them. This invention also relates to the use of these proteins and polypeptides in immunogenic compositions, diagnostic methods, and diagnostic kits. The genus Bordetella includes seven species. The most studied species are B. pertussis, B. parapertussis, and B. bronchiseptica. B. pertussis is responsible for respiratory infections only in humans. B. parapertussis causes infections in humans and sheep, and B. bronchiseptica infects many animal species, including humans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Purification of a pertussis outer membrane protein Inventor(s): Chong, Pele; (Richmond Hill, CA), Fahim, Raafat; (Mississauga, CA), Jackson, Gail; (Richmond Hill, CA), Klein, Michel; (Willowdale, CA), Tan, Larry; (Mississauga, CA), Voss, John; (Aurora, CA) Correspondence: Michael S. Greenfield; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20010051163 Date filed: June 25, 2001 Abstract: Pertactin (formerly 69 kDa protein) is recovered in stable biologically pure form having no detectable adenylate cyclase activity from fermentation broth from the fermentation of Bordetella pertussis as well as from the cells. The broth is processed to selectively remove pertussis toxin (PT) and filamentous haemagglutinin (FHA), the pertactin is precipitated by ammonium sulphate and the precipitate is dissolved in buffer at pH 6.0 to 8.5, the solution then is passed through hydroxyapatite and QSepharose.RTM. chromatograph columns before final ultrafiltration. Cells are extracted

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with urea and the extract ultrafiltered and diafiltered. The pertactin is precipitated from the extract and the precipitate processed as above. In a variation, the broth is contacted with ammonium sulphate to precipitate pertactin, PT and FHA, the precipitate is dissolved and the PT and FHA selectively removed, before the solution is passed to the chromatograph columns. Excerpt(s): The present invention relates to a novel process for the purification of an outer membrane protein of Bordetella pertussis, having a molecular weight of approximately 69,000 Daltons, formerly called the 69kDa protein and now called pertactin, and obtained from the fermentation broth and cellular extracts of the said organism. The protein obtained by the process is to be used in a "component" vaccine to protect against the disease of whooping cough. The disease of whooping cough or pertussis is a result of infection by Bordetella pertussis, and is a serious and debilitating human disease particularly in young children. For the last fifty years the disease has been controlled through large-scale immunization programmes. The current licensed vaccine in North America is a "whole cell" vaccine prepared by growing the organism in fermentors and then treating the resulting B. pertussis cells with chemical agents, such as formaldehyde, to kill the organism and inactivate toxic proteins. The cells are resuspended and then used directly or in combination with other antigens. This vaccine, although highly efficacious, has been associated with clinical symptoms that include fever, local reactions, high-pitched crying and convulsions. Despite the fact that there is no proven relation between these symptoms and the vaccine, there has been decreased public acceptance of this vaccine and in a number of countries, e.g. Japan, Sweden and the U.K., decreased immunization has led to outbreaks of the disease. The need for a more defined vaccine has been recognized and considerable effort has been directed by several manufacturers and researchers towards the development of an efficacious pertussis vaccine that consists of a small number of highly purified proteins. This vaccine has been termed a component vaccine. This search has been hampered by a lack of information on the mechanism of pathogenesis of B. pertussis. Many virulence associated factors, such as pertussis toxin (PT), also known as lymphocytosis promoting factor (LPF), filamentous haemagglutinin (FHA), adenylate cyclase, lipopolysaccharide, agglutinogens and other outer membrane proteins have been suggested for inclusion in an "acellularl" vaccine, which is less defined than the component vaccine. Much of the work on acellular vaccines has concentrated on a PT-based vaccine. Results of a recent clinical trial have indicated that a vaccine consisting entirely of PT-toxoid only partially protected children from the infection. A PT/FHA combination showed slightly higher efficacy but this was still lower than that obtained for the whole-cell vaccine. 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 whooping cough, 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 “whooping cough” (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 whooping cough.

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You can also use this procedure to view pending patent applications concerning whooping cough. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON WHOOPING COUGH Overview This chapter provides bibliographic book references relating to whooping cough. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on whooping cough include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “whooping cough” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “whooping cough” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “whooping cough” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Adverse Effects of Pertussis and Rubella Vaccines by Christopher P. Howson (Editor), et al; ISBN: 0309044995; http://www.amazon.com/exec/obidos/ASIN/0309044995/icongroupinterna

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New pertussis vaccine offers prevention alternative (SuDoc HE 20.4010/A: P 43) by Rebecca D. Williams; ISBN: B00010HPAC; http://www.amazon.com/exec/obidos/ASIN/B00010HPAC/icongroupinterna

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Pathogenesis and Immunity in Pertussis by Pathogenesis and Immunity in P, et al; ISBN: 0471918202; http://www.amazon.com/exec/obidos/ASIN/0471918202/icongroupinterna

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Pointers to the Common Remedies: Chicken Pox, Diphtheria, Erysipelas, Herpes Zoster, Measles, Mumps, Scarlet Fever, Small-pox, Typhoid and Typhoid Conditions, Vaccination, Whooping Cough by M.L. Tyler, Douglas M. Borland (Editor) (1930);

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ISBN: 0946717451; http://www.amazon.com/exec/obidos/ASIN/0946717451/icongroupinterna •

Proceedings of the Sixth International Symposium on Pertussis : (SuDoc HE 20.4002:P 43/2) by U.S. Dept of Health and Human Services; ISBN: B00010DYFM; http://www.amazon.com/exec/obidos/ASIN/B00010DYFM/icongroupinterna

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Whooping Cough by Elizabeth Laskey; ISBN: 1403402779; http://www.amazon.com/exec/obidos/ASIN/1403402779/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 “whooping cough” (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:10 •

A study in active immunization against pertussis [by] Pearl Kendrick and Grace Eldering, with statistical analyses by Anthony J. Borowski. Author: Kendrick, Pearl.; Year: 1974; [Grand Rapids, Mich., 1938?]

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Diphtheria and pertussis vaccination; report.; Year: 1959; Geneva, World Health Organization, 1953

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International Symposium on Pertussis Author: Manclark, Charles R.; Year: 1957; Bethesda, Md.: U. S. Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health; Washington: for sale by the Supt. of Docs., U. S. Govt. Print. Off., [1979?]

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Measles and whooping cough; incidence, fatality and death rates in thirty-two cities of the United States, in relation to administrative procedures intended for control. 1924-1933. Report prepared by Haven Emerson. Author: American Public Health Association. Committee on Administrative Practice. Sub-Committee on Evaluation of Health Department Practices.; Year: 1970; [New York, 1934?]

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Pertussis: description and evaluation based on surveillance data of 1997 and 1998 Author: Neppelenbroek, S. E.; Year: 1956; Bilthoven, Netherlands: National Institute of Public Health and the Environment, [1999]

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Pertussis in infancy as a cause of behaviour disorders in children. Author: Annell, Anna-Lisa.; Year: 1953; [Uppsala, Almqvist; Wiksell, 1953] http://www.amazon.com/exec/obidos/ASIN/3805564813/icongroupinterna

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Proceedings of the Fourth International Symposium on Pertussis: a joint meeting of the International Association of Biological Standardization and the World Health Organization, held at the executive board room of the World Health Organization,

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Geneva, Switzerland, 25-27 Sept. 1984 Author: Manclark, Charles R.; Year: 1953; Basel; New York: Karger, c1985; ISBN: 3805542100 http://www.amazon.com/exec/obidos/ASIN/3805542100/icongroupinterna •

Proceedings of the Sixth International Symposium on Pertussis, Jack Masur Auditorium, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, September 26-28, 1990 Author: Center for Biologics Evaluation and Research (U.S.); Year: 1956; Bethesda, Md.: Dept. of Health and Human Services, United States Public Health Service, Food and Drug Administration, 1990

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Report of the Task Force on Pertussis and Pertussis Immunization, 1988. Author: American Academy of Pediatrics. Task Force on Pertussis and Pertussis Immunization.; Year: 1958; Elk Grove Village, Ill.: American Academy of Pediatrics, [c1988]

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Studies on pertussis with special reference to its immunological prevention, by Keizo Nobechi. Author: Japan. Nihon Gakujutsu Kaigi. Hyakunichi-seki Kenky¯u Iinkai.; Year: 1969; Tokyo, Japan Society for Promotion of Science, 1955

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Task force report on pertussis: hearing before the committee on Labor and Human Resources, United States Senate, Ninety-eighth Congress, first session on examination of the task force report on the vaccine pertussis, July 22, 1983. Author: United States. Congress. Senate. Committee on Labor and Human Resources.; Year: 1963; Washington: U.S. G.P.O., 1983

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The epidemiology of pertussis and pertussis immunization in the United Kingdom and the United States: a comparative study Author: Cherry, James D. (James Donald),; Year: 1964; Chicago: Year Book Medical Publishers, c1984

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The pertussis epidemic in 1996: description and evaluation based on surveillance data from 1976 to 1996 Author: Melker, H. E. de.; Year: 1934; Bilthoven: National Institute of Public Health and the Environment, [1997]

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Whooping cough: reports from the Committee on Safety of Medicines and the Joint Committee on Vaccination and Immunisation. Author: Great Britain. Committee on Safety of Medicines.; Year: 1964; London: H.M.S.O., 1981; ISBN: 0113207646

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Whooping cough in Finland, 1920-1978: statistical and epidemiological studies Author: Huovila, Riitta.; Year: 1962; Helsinki: [s.n.]; Stockholm, Sweden: Distributed by Almqvist; Wiksell Periodical Co., 1982

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Whooping cough vaccination: review of the evidence on whooping cough vaccination Author: Great Britain. Joint Committee on Vaccination and Immunisation.; Year: 1954; London: H. M. Stationary Off., 1977

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Whooping cough. Author: Lapin, Joseph Harris,; Year: 1937; Springfield, Ill., Thomas, 1943

Chapters on Whooping Cough In order to find chapters that specifically relate to whooping cough, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and whooping cough 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 “whooping cough” (or synonyms) into the “For these words:” box.

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CHAPTER 7. MULTIMEDIA ON WHOOPING COUGH Overview In this chapter, we show you how to keep current on multimedia sources of information on whooping cough. 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.

Bibliography: Multimedia on Whooping Cough 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 whooping cough (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 whooping cough: •

Identification of Bordetella pertussis [slide] Source: Center for Disease Control, Bureau of Laboratories, Laboratory Training and Consultation Division; Year: 1979; Format: Slide; [Atlanta, Ga.]: The Center, [1979]

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Update on pertussis [videorecording]: the disease and vaccine Source: presented by the Department of Pediatrics, Emory University, School of Medicine; Year: 1986; Format: Videorecording; Atlanta, Ga.: The University, 1986

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Whooping cough [videorecording] Source: a presentation of Films for the Humanities & Sciences; produced in cooperation with the Pediatric Infectious Diseases Society; ITV, Information Television Network; Year: 1998; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1998

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CHAPTER 8. PERIODICALS AND NEWS ON WHOOPING COUGH Overview In this chapter, we suggest a number of news sources and present various periodicals that cover whooping cough.

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

Whooping cough on rise in U.S. - study Source: Reuters Health eLine Date: December 09, 2003

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Pertussis incidence on rise in U.S. Source: Reuters Medical News Date: December 09, 2003

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Oxygen treatment may not help with whooping cough Source: Reuters Health eLine Date: December 08, 2003

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Parents, older siblings may be transmitting pertussis to UK infants Source: Reuters Medical News Date: August 27, 2003

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CDC: Whooping cough outbreak in Illinois adults Source: Reuters Health eLine Date: January 09, 2003

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Whooping cough threatens thousands in Afghanistan Source: Reuters Health eLine Date: January 06, 2003

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UN probes deaths in Afghan whooping cough epidemic Source: Reuters Health eLine Date: October 22, 2002

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Whooping cough may be common in French adults Source: Reuters Health eLine Date: September 02, 2002

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Seventeen infants died from pertussis in US in 2000 Source: Reuters Medical News Date: July 18, 2002

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CDC: 17 US babies died from whooping cough in 2000 Source: Reuters Health eLine Date: July 18, 2002

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Whooping cough vaccine cuts infection in Senegal Source: Reuters Health eLine Date: June 05, 2002

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Whooping cough found in Russian-born adopted baby Source: Reuters Health eLine Date: May 09, 2002

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Pertussis found in Russian-born adopted infant Source: Reuters Medical News Date: May 09, 2002

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Whooping cough increasing among US infants Source: Reuters Health eLine Date: February 01, 2002

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UK introduces pre-school booster pertussis vaccination Source: Reuters Medical News Date: October 16, 2001

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UK introduces pertussis booster vaccination program for preschoolers Source: Reuters Industry Breifing Date: October 16, 2001

Periodicals and News

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Pertussis a common cause of prolonged cough Source: Reuters Medical News Date: July 16, 2001

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Wellcome whooping cough vaccine was unsafe, newspaper claims Source: Reuters Industry Breifing Date: July 09, 2001

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Resistance to whooping cough vaccine growing Source: Reuters Health eLine Date: May 22, 2001

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Study: Whooping cough more common than believed Source: Reuters Health eLine Date: May 18, 2001

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Whooping cough vaccine advised in Massachusetts Source: Reuters Health eLine Date: October 16, 2000

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Genomics One, Canadian university to sequence whooping cough genome Source: Reuters Industry Breifing Date: August 09, 2000

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Virulence factor of whooping cough pathogen may subvert immunity in the lung Source: Reuters Medical News Date: March 13, 2000

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Vaccine reduces transmission of whooping cough Source: Reuters Health eLine Date: January 24, 2000

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Pyloric stenosis risk linked to erythromycin prophylaxis for pertussis Source: Reuters Medical News Date: December 20, 1999

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Acellular pertussis vaccine shows fewer severe side effects Source: Reuters Medical News Date: November 22, 1999

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New whooping cough vaccine cuts side effect risks Source: Reuters Health eLine Date: November 19, 1999

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Persistent cough in adults may be whooping cough Source: Reuters Health eLine Date: November 12, 1999

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Whooping cough "common" among adults Source: Reuters Health eLine Date: August 26, 1998

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Bordetella-associated whooping cough common in immunized population Source: Reuters Medical News Date: August 19, 1998

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Pertussis vaccine not tied to increased asthma incidence in infants Source: Reuters Medical News Date: August 14, 1998

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"Small" allergy risk from pertussis vaccine Source: Reuters Health eLine Date: August 13, 1998

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Moms Choose Acellular Pertussis Vaccine Source: Reuters Health eLine Date: March 04, 1998

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Anti-Vaccine Movements Lead To Increased Prevalence Of Pertussis Source: Reuters Medical News Date: February 02, 1998

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Pertussis Vaccine Controversy Continues Source: Reuters Health eLine Date: January 30, 1998

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FDA Approves Acellular Whooping Cough Vaccine Source: Reuters Health eLine Date: July 31, 1996

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Unvaccinated Adults May Serve As Reservoirs Of Pertussis Source: Reuters Medical News Date: November 20, 1995 The NIH

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

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

Academic Periodicals covering Whooping Cough Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to whooping cough. In addition to these sources, you can search for articles covering whooping cough 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 9. 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 whooping cough. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with whooping cough. 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.).

118 Whooping Cough

The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to whooping cough: 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

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

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. 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

121

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 Institute11: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

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

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•

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

•

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

The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “whooping cough” (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 4911 222 39 24 0 5196

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “whooping cough” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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 Biologists19 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.20 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.21 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/.

19 Adapted 20

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. 21 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 whooping cough 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 whooping cough. 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 whooping cough. 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 “whooping cough”:

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•

Guides on whooping cough Whooping Cough http://www.nlm.nih.gov/medlineplus/whoopingcough.html

•

Other guides Childhood Immunization http://www.nlm.nih.gov/medlineplus/childhoodimmunization.html Diphtheria http://www.nlm.nih.gov/medlineplus/diphtheria.html Tetanus http://www.nlm.nih.gov/medlineplus/tetanus.html

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

General/Overviews Pertussis (Whooping Cough) Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZPWVII1AC& sub_cat=286

•

Specific Conditions/Aspects Diphtheria, Tetanus, and Pertussis: Health Information for International Travel, 2003-2004 Source: Centers for Disease Control and Prevention http://www.cdc.gov/travel/diseases/dtp.htm

•

Children Pertussis (Whooping Cough) Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/whooping_cough.html Woes of Whooping Cough Source: Nemours Foundation http://kidshealth.org/kid/health_problems/heart/whooping_cough.html

•

Journals/Newsletter Current Vaccine Delays and Shortages Source: National Immunization Program http://www.cdc.gov/nip/news/shortages/default.htm

•

Latest News Oxygen Treatment May Not Help with Whooping Cough Source: 12/08/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_15017 .html

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Whooping Cough on Rise in U.S. Source: 12/09/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_15047 .html •

Organizations Centers for Disease Control and Prevention, National Immunization Program Source: National Immunization Program http://www.cdc.gov/nip/ National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/

•

Pictures/Diagrams Pertussis Source: Immunization Action Coalition http://www.immunize.org/images/ca.d/ipcd1861/img0007.htm

•

Prevention/Screening Diphtheria, Tetanus, and Pertussis Vaccines http://www.cdc.gov/nip/publications/VIS/vis-dtp.pdf Improved Pertussis Vaccines: Enhancing Protection Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/publications/discovery/tpertus.htm Newly Formulated DTaP (Diphtheria, Tetanus, and Pertussis) Vaccine Approved with Only Trace Amounts of Thimerosal Source: Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2001/NEW00756.html Preventing Whooping Cough Source: American Academy of Pediatrics http://www.medem.com/search/article_display.cfm?path=n:&mstr=/ZZZT3AWT EDC.html&soc=AAP&srch_typ=NAV_SERCH

•

Research Measles and Pertussis Risk Higher for Children with Personal Exemptions From Immunizations Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZL66641HC& sub_cat=620

•

Statistics FASTATS: Whooping Cough Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/whooping.htm

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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 whooping cough. 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: •

Be Wise, Immunize!: Vaccinate on Time Source: Cleveland, OH: Learning Curve of Weingart Design. 199x. [2 p.]. Contact: Available from Learning Curve of Weingart Design. 4614 Prospect Avenue, Number 421, Cleveland, OH 44103-4314. (800) 795-9295. Fax (216) 881-7177. Website: www.learningcurve1.com. PRICE: $10.00 for a pack of 100; single copies are not available. Summary: This oversized bookmark lists the latest recommendations for pediatric immunizations from the Centers for Disease Control (CDC). The bookmark reminds parents that getting the shots (vaccinations) and getting all of them, is one of the most important things they can do for their babies. The front of the bookmark lists the age and recommended immunizations. The reverse side lists each of the immunizations and briefly notes what each one covers. Included are vaccines against hepatitis B, which causes liver damage; Hib (haemophilus influenzae b), which causes brain infection and brain damage; DTP or DTaP, which protects against diphtheria (serious breathing problems that can lead to paralysis and heart failure), pertussis (whooping cough), and tetanus (causes painful muscle spasms leading to lockjaw); polio (OPV), a disease that can paralyze arms and legs; MMR, measles, mumps, and rubella (rubella is German measles, a more serious form of measles that can lead to birth defects in babies); and varicella, or chicken pox. The schedule printed on the front of the bookmark is recommended by the American Academy of Pediatrics and the American Academy of Family Physicians. 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 “whooping cough” (or synonyms). The following was recently posted:

Patient Resources

•

131

(1) Pertussis vaccination: use of acellular pertussis vaccines among infants and young children Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1997 March 28 (updated 2000 Nov); 25 pages; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=839&nbr=60& string=whooping+AND+cough 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 whooping cough. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

132 Whooping Cough

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 “whooping cough” (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 “whooping cough”. 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 “whooping cough” (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 “whooping cough” (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.22

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

22

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)23: •

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/

23

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

Finding Medical Libraries

135

•

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/

136 Whooping Cough

•

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/

Finding Medical Libraries

137

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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/

138 Whooping Cough

•

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

139

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 whooping cough: •

Basic Guidelines for Whooping Cough Pertussis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001561.htm Pertussis - vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002027.htm

•

Signs & Symptoms for Whooping Cough Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Bluish skin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Convulsion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm

140 Whooping Cough

Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Coughing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Runny nose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003051.htm Seizure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Slight fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Whooping Cough CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Throat swab culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003746.htm White blood cell count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003643.htm

Online Glossaries 141

•

Background Topics for Whooping Cough Allergic reaction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000005.htm Choking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000047.htm Contraindications Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002314.htm Diphtheria immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002018.htm DT vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002021.htm DTaP vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002021.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Nose bleeds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000020.htm Pertussis immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002027.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm TD vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002021.htm Tetanus immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002031.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/

142 Whooping Cough

•

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

143

WHOOPING COUGH DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. [NIH] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [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] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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]

144 Whooping Cough

Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [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] 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]

Dictionary 145

Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] 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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the

146 Whooping Cough

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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Apnoea: Cessation of breathing. [EU] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Auscultation: Act of listening for sounds within the body. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Proteins: Proteins found in any species of bacterium. [NIH]

Dictionary 147

Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form 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] 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]

Beta-Defensins: Defensins found mainly in epithelial cells. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] 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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH]

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Birth Rate: The number of births in a given population per year or other unit of time. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bordetella: A genus of gram-negative, aerobic bacteria whose cells are minute coccobacilli. It consists of both parasitic and pathogenic species. [NIH] Bordetella bronchiseptica: A species of Bordetella that is parasitic and pathogenic. It is found in the respiratory tract of domestic and wild mammalian animals and can be transmitted from animals to man. It is a common cause of bronchopneumonia in lower animals. [NIH] Bordetella pertussis: A species of gram-negative, aerobic bacteria that is the causative agent of whooping cough. Its cells are minute coccobacilli that are surrounded by a slime sheath. [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]

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] 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] Bronchopneumonia: A name given to an inflammation of the lungs which usually begins in the terminal bronchioles. These become clogged with a mucopurulent exudate forming consolidated patches in adjacent lobules. The disease is frequently secondary in character,

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following infections of the upper respiratory tract, specific infectious fevers, and debilitating diseases. In infants and debilitated persons of any age it may occur as a primary affection. Called also bronchial pneumonia, bronchiolitis, bronchoalveolitis, bronchopneumonitis, catarrhal pneumonia, lobular pneumonia, capillary bronchitis and vesicular bronchiolitis. [EU]

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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capital Financing: Institutional funding for facilities and for equipment which becomes a part of the assets of the institution. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [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] Carbohydrate Sequence: The sequence of carbohydrates within polysaccharides, glycoproteins, and glycolipids. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [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] 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 Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] 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] Cerebellar: Pertaining to the cerebellum. [EU]

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Cerebral: Of or pertaining of the cerebrum or the 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] 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] 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] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliated cells: Epithelial cells with fine hair-like strands on their free borders. [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] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH]

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Colloidal: Of the nature of a colloid. [EU] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement 3: The fourth component to attach in the complement reaction sequence. It is a beta-globulin with a sedimentation coefficient of 5.5, a molecular weight of 185,000 and a serum concentration of 1.3 micrograms/ml. Its fragments have anaphylatoxic, chemotactic, and histaminic action and affect smooth muscle. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH]

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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] 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] Cultured cell line: Cells of a single type that have been grown in the laboratory for several generations (cell divisions). [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] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH]

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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] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diphtheria-Tetanus-Pertussis Vaccine: A vaccine consisting of diphtheria toxoid, tetanus toxoid, and whole-cell pertussis vaccine. The vaccine protects against diphtheria, tetanus, and whooping cough. [NIH]

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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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [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] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enteric bacteria: Single-celled microorganisms that lack chlorophyll. Some bacteria are capable of causing human, animal, or plant diseases; others are essential in pollution control because they break down organic matter in the air and in the water. [NIH] Enterobactin: An iron-binding cyclic trimer of 2,3-dihydroxy-N-benzoyl-L-serine. It is produced by E. coli and other enteric bacteria. [NIH]

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Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] 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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrina: A genus of leguminous shrubs or trees, mainly tropical, yielding certain alkaloids, lectins, and other useful compounds. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [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

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peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [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] Extraction: The process or act of pulling or drawing out. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] 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]

Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [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]

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Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gastric: Having to do with the stomach. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [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] 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]

Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a

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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-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety. [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] 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] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment

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of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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] 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]

Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [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] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Host-Parasite Relations: The interactions between two organisms, one of which lives at the expense of the other. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU]

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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] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience

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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] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH]

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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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [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] Islet: Cell producing insulin in pancreas. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH]

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Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] 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] 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] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [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] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkages: 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] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lockjaw: Inability to open the mouth due to tonic contracture of the muscles of the jaw. [NIH]

Locomotion: Movement or the ability to move from one place or another. It can refer to

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humans, vertebrate or invertebrate animals, and microorganisms. [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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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]

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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] Mental Health: The state wherein the person is well adjusted. [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] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] 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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] 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] Monocyte: A type of white blood cell. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous

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chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [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] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] 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] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [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]

Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]

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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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] 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] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [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]

Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paralysis: Loss of ability to move all or part of the body. [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] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A

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sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] 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] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotypes: An organism as observed, i. e. as judged by its visually perceptible characters resulting from the interaction of its genotype with the environment. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphates: Inorganic salts of phosphoric acid. [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] Physiologic: Having to do with the functions of the body. When used in the phrase

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"physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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] Population Density: Number of individuals in a population relative to space. [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] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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,

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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] Practice Management: Business management of medical and dental practices that may include capital financing, utilization management, and arrangement of capitation agreements with other parties. [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] 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] 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] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [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] 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

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macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [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]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [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] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [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] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be

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cancer in the body. [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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Sounds: Noises, normal and abnormal, heard on auscultation over any part of the respiratory tract. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] 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] Rod: A reception for vision, located in the retina. [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] Schools, Medical: Educational institutions for individuals specializing in the field of medicine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [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] 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

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type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] 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] 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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU]

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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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] 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]

Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Supplementation: Adding nutrients to the diet. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Systemic: Affecting the entire body. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic

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muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetranitromethane: Corrosive oxidant, explosive; additive to diesel and rocket fuels; causes skin and lung irritation; proposed war gas. A useful reagent for studying the modification of specific amino acids, particularly tyrosine residues in proteins. Has also been used for studying carbanion formation and for detecting the presence of double bonds in organic compounds. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] 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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or

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animals. [NIH] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] 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] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH]

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Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [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] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] 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] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] 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] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [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] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Whole cell vaccine: Vaccine made from whole tumor cells that have been changed in the laboratory. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] World Health: The concept pertaining to the health status of inhabitants of the world. [NIH] World Health Organization: A specialized agency of the United Nations designed as a

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coordinating authority on international health work; its aim is to promote the attainment of the highest possible level of health by all peoples. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

179

INDEX A Aberrant, 9, 143 Acceptor, 83, 143, 167 Acetylcholine, 60, 143, 166 Adaptation, 7, 92, 143 Adenine, 83, 143 Adenosine, 83, 143, 168 Adenosine Diphosphate, 83, 143 Adenosine Monophosphate, 83, 143 Adenylate Cyclase, 13, 19, 20, 21, 26, 60, 61, 77, 92, 96, 98, 101, 102, 143, 150 Adhesions, 8, 143 Adjustment, 143 Adjuvant, 60, 78, 143 Adrenal Medulla, 61, 143, 155 Adverse Effect, 90, 105, 143, 173 Aerobic, 143, 148 Aerosol, 18, 100, 143 Aetiology, 36, 144 Affinity, 144, 173 Age Groups, 5, 144 Aged, 80 and Over, 144 Agglutinins, 36, 144 Airway, 6, 34, 86, 144 Algorithms, 144, 147 Alimentary, 144, 162, 168 Alkaline, 144, 145, 149 Alkaloid, 144, 149 Allergen, 144, 172 Alpha-Defensins, 144, 153 Alternative medicine, 114, 144 Aluminum, 16, 144 Amine, 144, 159 Amino Acid Sequence, 18, 144, 145, 157 Amino Acids, 86, 100, 144, 145, 156, 157, 168, 169, 170, 173, 175, 176 Ammonia, 144, 145, 176 Amplification, 76, 145 Anaerobic, 145, 158 Anaesthesia, 34, 46, 47, 145, 161 Anal, 145, 155, 156 Anaphylatoxins, 145, 151 Anemia, 145, 158, 164 Anesthesia, 144, 145 Animal model, 4, 7, 145 Anions, 145, 162 Annealing, 145, 169 Anoxia, 86, 145

Anthrax, 98, 145 Antibacterial, 10, 145, 162, 167 Antibiotic, 5, 6, 145, 148, 155 Anticoagulant, 146, 170 Antigen-Antibody Complex, 146, 151 Antimicrobial, 6, 10, 16, 25, 146, 150, 153 Apnoea, 94, 146 Aqueous, 146, 147, 152, 163 Arginine, 61, 145, 146, 166 Arterial, 146, 170 Arteries, 146, 148, 152, 165 Assay, 13, 16, 17, 18, 21, 79, 146, 160 Asymptomatic, 96, 146 Ataxia, 26, 146, 175 Auscultation, 146, 172 Autoimmune disease, 90, 146 Autonomic, 143, 146 B Bacillus, 14, 81, 145, 146, 148 Bacterial Infections, 6, 146, 163 Bacterial Physiology, 143, 146 Bacterial Proteins, 84, 146 Bacterial toxin, 78, 147 Bacteriophage, 147, 177 Bacteriostatic, 92, 147, 155 Bacterium, 6, 81, 89, 90, 92, 146, 147 Basal Ganglia, 146, 147 Basal Ganglia Diseases, 146, 147 Base, 16, 87, 143, 147, 157, 163 Basophils, 147, 158, 163 Benign, 147, 158 Beta-Defensins, 6, 147, 153 Bile, 147, 159, 163 Biochemical, 9, 83, 147, 163 Biological response modifier, 147, 162 Biotechnology, 9, 22, 45, 106, 114, 123, 147 Biotin, 60, 147, 167 Biotypes, 147, 158 Birth Rate, 23, 148 Blood Cell Count, 148, 158 Blood Coagulation, 148, 149, 175 Blood pressure, 148, 160, 173 Blood vessel, 148, 150, 154, 164, 168, 173, 175, 176 Blot, 13, 18, 148, 167 Body Fluids, 148, 173 Bone Marrow, 88, 148, 160, 164

180 Whooping Cough

Bordetella bronchiseptica, 6, 8, 15, 18, 20, 21, 77, 94, 101, 148 Bradykinin, 148, 166 Branch, 137, 148, 164, 171, 174, 175 Broad-spectrum, 148, 167 Bronchi, 148, 155, 176 Bronchial, 19, 28, 148, 149, 159 Bronchiseptica, 6, 8, 76, 77, 82, 94, 101, 148, 168 Bronchopneumonia, 148 C Calcium, 16, 98, 149, 151, 168 Calmodulin, 61, 149 Capital Financing, 149, 170 Capsaicin, 61, 149 Capsular, 88, 89, 149 Carbohydrate, 86, 91, 149, 157, 169 Carbohydrate Sequence, 87, 149 Carboxy, 100, 149 Carcinogenic, 149, 161, 167, 170 Cardiac, 60, 149, 155, 159, 166 Catecholamines, 143, 149 Cations, 149, 162 Causal, 149, 155, 173, 174 Cell Adhesion, 149, 162 Cell Division, 146, 149, 152, 164, 169, 170 Cell proliferation, 4, 149 Cellulose, 149, 169 Cerebellar, 26, 146, 149, 171 Cerebral, 49, 146, 147, 150, 152, 155, 164, 174 Cerebrum, 150 Cervical, 150 Chemotactic Factors, 150, 151 Cholera, 17, 78, 150, 173, 177 Cholera Toxin, 17, 78, 150 Chromosomal, 87, 145, 150, 169 Chromosome, 150, 158, 163 Chronic, 9, 98, 150, 154, 161, 174, 177 Ciliary, 86, 150 Ciliated cells, 86, 94, 150 Ciprofloxacin, 16, 150 Circulatory system, 150, 162 Clinical trial, 3, 5, 8, 102, 123, 150, 171 Cloning, 15, 80, 87, 100, 147, 150 Cofactor, 150, 170, 175 Cohort Studies, 150, 155 Colloidal, 151, 154 Communicable disease, 99, 151 Complement, 4, 11, 25, 36, 83, 145, 151, 157, 162, 172 Complement 3, 4, 151

Complementary and alternative medicine, 65, 71, 151 Complementary medicine, 65, 151 Complete remission, 151, 171 Computational Biology, 123, 151 Conjunctiva, 151, 161 Connective Tissue, 148, 151, 152, 157, 164 Consciousness, 152, 174 Consumption, 152, 153 Contamination, 84, 152 Contracture, 152, 163 Contraindications, ii, 32, 152 Convulsions, 80, 81, 102, 140, 152 Convulsive, 21, 80, 152 Coordination, 5, 152 Coronary, 152, 165 Coronary Thrombosis, 152, 165 Cortex, 146, 152, 171 Cortical, 152, 172, 175 Cranial, 152, 158, 162 Cross-Sectional Studies, 152, 155 Cultured cell line, 8, 152 Cultured cells, 99, 152 Curative, 152, 172, 175 Cutaneous, 145, 152 Cyclic, 83, 143, 149, 152, 154, 158, 166 Cysteine, 11, 152, 153 Cytoplasm, 8, 147, 150, 152, 155, 158, 166 Cytoskeleton, 152, 162 Cytotoxicity, 9, 21, 153 D Databases, Bibliographic, 123, 153 Deamination, 153, 176 Decarboxylation, 153, 159 Defense Mechanisms, 6, 153, 162 Defensins, 6, 144, 147, 153 Degenerative, 153, 159 Dehydration, 150, 153 Deletion, 8, 153 Denaturation, 153, 169 Detoxification, 83, 153 Developed Countries, 77, 97, 98, 153 Diagnostic procedure, 42, 75, 114, 153 Diarrhea, 98, 140, 153, 161 Diffusion, 153, 176 Digestion, 144, 147, 153, 163, 174 Dihydroxy, 153, 154 Diphtheria, 15, 17, 24, 30, 43, 60, 67, 78, 95, 105, 106, 118, 128, 129, 130, 141, 153 Diphtheria Toxin, 78, 153 Diphtheria-Tetanus-Pertussis Vaccine, 15, 67, 153

Index 181

Diploid, 154, 169 Direct, iii, 12, 13, 14, 17, 117, 154, 171 Disease Progression, 154, 177 Drug Interactions, 118, 154 E Edema, 154, 166 Effector, 9, 143, 151, 154 Efficacy, 5, 9, 13, 15, 16, 44, 54, 81, 82, 99, 102, 154 Effusion, 154, 164 Electrolyte, 154, 159, 173 Electrons, 147, 154, 162, 167, 171 Electrophoresis, 10, 13, 19, 21, 25, 46, 154 Embryo, 154, 161 Emollient, 154, 157 Encapsulated, 10, 154 Encephalopathy, 81, 82, 86, 94, 154 Endemic, 150, 154, 164, 174 Endothelium, 154, 166 Endothelium-derived, 154, 166 Endotoxin, 81, 90, 99, 154 Enteric bacteria, 154 Enterobactin, 5, 6, 154 Environmental Health, 122, 124, 155 Enzymatic, 100, 149, 151, 155, 159, 169 Enzyme, 5, 12, 13, 14, 17, 40, 49, 79, 143, 154, 155, 156, 158, 159, 169, 170, 174, 175, 177, 178 Enzyme-Linked Immunosorbent Assay, 12, 13, 14, 40, 49, 79, 155 Eosinophils, 155, 158, 163 Epidemic, 10, 25, 26, 28, 36, 41, 52, 57, 107, 112, 155, 174 Epidemiologic Studies, 8, 155 Epidemiological, 4, 21, 46, 50, 107, 155 Epinephrine, 155, 176 Epithelial, 6, 7, 11, 14, 19, 21, 61, 147, 150, 155, 159 Epithelial Cells, 6, 7, 11, 19, 21, 61, 147, 150, 155, 159 Epithelium, 6, 154, 155 Epitope, 16, 28, 80, 83, 90, 100, 155 Erythrina, 70, 155 Erythrocyte Indices, 148, 155 Erythrocytes, 145, 148, 155, 172 Erythromycin, 11, 33, 113, 155 Ethanol, 156 Exhaustion, 156, 164 Exogenous, 156, 170 Exotoxin, 7, 156 Extracellular, 151, 152, 156, 162, 173 Extracellular Matrix, 151, 152, 156, 162

Extraction, 92, 96, 156 F Family Planning, 123, 156 Fat, 148, 156, 163, 173 Fatigue, 156, 158 Fermentation, 84, 85, 92, 101, 102, 156 Fixation, 156, 172 Flushing, 85, 156 Fractionation, 81, 156 Fungi, 5, 156, 165, 178 G Ganglia, 143, 147, 157, 166 Gangrenous, 157, 173 Gas, 145, 153, 157, 160, 166, 175, 177 Gastric, 157, 159 Gastrointestinal, 148, 150, 155, 156, 157, 164, 174, 177 Gene, 5, 6, 7, 8, 10, 76, 80, 81, 83, 84, 93, 100, 106, 147, 157, 167 Gene Expression, 6, 8, 84, 157 Genetic Code, 157, 167 Genetic Engineering, 81, 147, 150, 157 Genetic testing, 157, 169 Genital, 14, 150, 157 Genotype, 84, 157, 168 Germ Cells, 157, 164, 167 Ginseng, 70, 157 Gland, 143, 157, 164, 167, 168, 172, 175 Glottis, 157, 168 Glucose, 149, 157, 159, 161, 162 Glycerol, 78, 157 Glycosidic, 89, 157 Governing Board, 157, 170 Graft, 157, 159 Gram-negative, 8, 77, 89, 90, 148, 157, 158, 167, 177 Gram-positive, 89, 158, 167 Granulocytes, 158, 177 Growth, 5, 7, 17, 82, 87, 92, 93, 145, 146, 147, 149, 158, 162, 169, 175, 176, 177 Guanosine Triphosphate, 83, 158 Guanylate Cyclase, 158, 166 H Haemophilus, 29, 130, 158 Haemophilus influenzae, 29, 130, 158 Hair follicles, 158, 177 Haploid, 158, 169 Headache, 158, 161 Health Status, 158, 177 Heart failure, 130, 158 Hematocrit, 148, 155, 158 Heme, 6, 158

182 Whooping Cough

Hemodiafiltration, 158, 176 Hemodialysis, 158, 176 Hemofiltration, 158, 176 Hemoglobin, 145, 148, 155, 158, 159 Hemostasis, 159, 162 Hepatitis, 17, 130, 159 Hepatocytes, 159 Heredity, 157, 159 Heterodimers, 90, 159, 162 Heterotrophic, 156, 159 Histamine, 78, 81, 83, 86, 100, 145, 159 Histidine, 159 Homologous, 6, 82, 159, 165, 172 Hormone, 155, 159, 161, 165, 168, 175 Horseradish Peroxidase, 155, 159 Host, 4, 6, 8, 21, 77, 78, 85, 100, 147, 153, 159, 160, 176, 177 Host-Parasite Relations, 7, 159 Humoral, 7, 9, 14, 15, 159 Humour, 159 Hybrid, 7, 14, 84, 87, 160, 167 Hybridization, 13, 160, 167 Hydrogen, 143, 144, 147, 149, 153, 160, 165, 167 Hydrolysis, 83, 160, 169, 170 Hypersensitivity, 144, 160, 172 Hypotension, 152, 160 Hypoxia, 81, 160, 175 I Id, 62, 68, 131, 136, 138, 160 Imidazole, 147, 159, 160 Immune function, 88, 160 Immune response, 4, 6, 7, 8, 9, 15, 43, 77, 88, 143, 146, 160, 172, 174, 176, 177 Immune Sera, 160 Immune system, 6, 160, 161, 164, 176, 177 Immunity, 5, 8, 9, 10, 13, 17, 19, 37, 40, 49, 60, 61, 82, 89, 92, 94, 101, 105, 113, 153, 160, 176 Immunoassay, 12, 79, 91, 155, 160 Immunodeficiency, 48, 88, 160 Immunofluorescence, 14, 28, 49, 160 Immunogen, 89, 160 Immunogenic, 77, 78, 83, 88, 101, 160 Immunoglobulin, 13, 14, 15, 18, 20, 31, 41, 42, 49, 79, 145, 160, 165 Immunologic, 4, 8, 89, 150, 160 Immunology, 7, 25, 28, 60, 91, 143, 144, 159, 161 In vitro, 8, 16, 98, 161, 169, 173 In vivo, 5, 7, 9, 98, 161 Incision, 161, 162

Incubation, 4, 161, 168 Incubation period, 4, 161, 168 Indicative, 105, 161, 176 Induction, 6, 9, 16, 61, 89, 161 Infancy, 28, 39, 51, 106, 161, 172 Infant, Newborn, 144, 161 Infarction, 152, 161, 165 Infectious Diarrhea, 98, 161 Inflammation, 148, 150, 153, 157, 159, 161, 166, 172, 177 Influenza, 5, 161 Ingestion, 145, 161 Inhalation, 143, 161 Initiation, 6, 161 Inorganic, 161, 165, 168 Insulin, 100, 161, 162 Insulin-dependent diabetes mellitus, 161, 162 Integrins, 4, 162 Intensive Care, 46, 162 Interferon, 19, 162 Interferon-alpha, 162 Intestinal, 98, 144, 150, 162 Intestines, 157, 162 Intoxication, 4, 162 Intracellular, 7, 16, 60, 161, 162, 165, 166, 177 Intracellular Membranes, 162, 165 Intracranial Pressure, 48, 162 Intramuscular, 162, 168 Intravenous, 141, 162, 168 Invasive, 89, 160, 162 Invertebrates, 91, 162 Involuntary, 147, 162, 166, 173 Ions, 98, 147, 149, 154, 160, 162 Islet, 78, 81, 83, 86, 162 Isoniazid, 29, 162 J Joint, 106, 107, 150, 163 K Kb, 82, 122, 163 Kinetic, 5, 163 L Labile, 17, 92, 151, 163 Laceration, 163, 174 Larynx, 157, 163, 176 Lectin, 61, 87, 91, 163, 165 Lens, 149, 163 Lethal, 153, 163 Leukocytes, 4, 147, 148, 150, 155, 158, 162, 163, 166 Leukocytosis, 25, 78, 163

Index 183

Levofloxacin, 16, 163 Library Services, 136, 163 Life cycle, 156, 163 Ligands, 86, 162, 163 Ligation, 4, 163 Linkages, 89, 159, 163 Lipid, 157, 161, 163 Lipopolysaccharide, 15, 20, 25, 102, 158, 163 Lipoprotein, 158, 163 Liver, 130, 147, 159, 163, 176 Localized, 99, 153, 154, 156, 161, 163, 169, 175 Lockjaw, 130, 163 Locomotion, 163, 169 Loop, 100, 164 Lymph, 88, 150, 154, 159, 164 Lymph node, 88, 150, 164 Lymphatic, 154, 161, 164, 174, 175 Lymphatic system, 164, 174, 175 Lymphocyte, 16, 88, 146, 164 Lymphocytosis, 37, 80, 81, 83, 86, 87, 88, 100, 102, 164 Lymphoid, 146, 164 Lytic, 164, 173, 177 M Malaria, 5, 164 Malaria, Falciparum, 164 Malaria, Vivax, 164 Malnutrition, 43, 49, 164 Mastitis, 147, 164, 173 Mediate, 8, 164 MEDLINE, 123, 164 Meiosis, 164, 166 Melanin, 164, 168, 176 Membrane, 8, 80, 84, 92, 95, 101, 102, 151, 156, 158, 163, 165, 166, 167, 172 Membrane Proteins, 102, 165 Mental Health, iv, 3, 122, 124, 165, 171 MI, 52, 88, 141, 165 Microbe, 165, 175 Microbiological, 5, 165 Microbiology, 6, 7, 8, 28, 29, 34, 41, 42, 44, 46, 49, 60, 61, 65, 143, 165 Microorganism, 80, 92, 100, 150, 165, 168, 177 Micro-organism, 87, 165, 172 Microscopy, 82, 159, 165 Microspheres, 10, 165 Modification, 84, 86, 93, 157, 165, 175

Molecular, 5, 6, 8, 10, 28, 29, 78, 81, 90, 92, 100, 102, 123, 125, 145, 147, 149, 151, 158, 165 Molecule, 88, 94, 146, 147, 151, 154, 155, 157, 160, 163, 165, 167, 169, 171, 177 Monoclonal, 14, 18, 38, 61, 165, 171 Monoclonal antibodies, 61, 165 Monocyte, 4, 165 Motor Activity, 152, 165 Mucins, 165, 172 Mucus, 86, 165 Multivalent, 95, 165 Mutagenesis, 83, 166 Mutagens, 166 Myalgia, 161, 166 Myocarditis, 153, 166 Myocardium, 165, 166 N Nasal Mucosa, 161, 166 Necrosis, 161, 165, 166 Need, 38, 102, 107, 132, 143, 166 Neonatal, 15, 35, 49, 166 Neonatal period, 49, 166 Nephrosis, 166 Nephrotic, 36, 166 Nephrotic Syndrome, 36, 166 Nerve, 85, 145, 146, 166, 176 Nervous System, 143, 157, 158, 166, 174 Neural, 159, 166 Neuromuscular, 143, 166 Neuromuscular Junction, 143, 166 Neutrophils, 11, 144, 158, 163, 166 Nitric Oxide, 14, 16, 85, 166 Nuclei, 154, 157, 166 Nucleic acid, 76, 81, 82, 157, 160, 166, 167, 177 Nucleic Acid Hybridization, 160, 167 Nucleus, 147, 152, 155, 164, 166, 167, 170, 174, 175 O Ofloxacin, 16, 167 Oligonucleotide Probes, 60, 167 Oncogenic, 162, 167 Operon, 76, 82, 167, 172 Organelles, 152, 167 Ossification, 167, 172 Ovary, 21, 60, 167 Oxidation, 143, 167 P Paediatric, 46, 47, 167 Palliative, 167, 175 Pancreas, 147, 161, 162, 167

184 Whooping Cough

Paralysis, 130, 167 Parasitic, 148, 167 Parathyroid, 167, 168, 172 Parathyroid Glands, 167, 168, 172 Parenteral, 45, 168 Paroxysmal, 81, 94, 168, 177 Partial remission, 36, 168, 171 Particle, 20, 168, 177 Pathogen, 4, 5, 6, 7, 8, 21, 90, 113, 161, 168 Pathogenesis, 4, 8, 9, 58, 83, 86, 94, 102, 105, 168 Patient Education, 130, 134, 136, 141, 168 Peptide, 6, 16, 79, 80, 91, 100, 150, 168, 169, 170 Perfusion, 160, 168 Pharmacologic, 89, 145, 168, 175 Pharynx, 161, 168 Phenotypes, 8, 168 Phenylalanine, 168, 176 Phosphates, 89, 168 Phosphorus, 149, 168 Physiologic, 168, 171 Plants, 91, 144, 153, 157, 163, 169, 175, 176 Plasma, 8, 146, 159, 169, 177 Plasma cells, 146, 169 Plasmid, 87, 169, 177 Platelet Aggregation, 20, 145, 166, 169 Platelets, 166, 169 Platinum, 164, 169 Polymerase, 10, 12, 17, 22, 169, 172 Polymerase Chain Reaction, 10, 12, 17, 22, 169 Polymers, 89, 169, 170 Polypeptide, 81, 90, 91, 144, 160, 169, 178 Polysaccharide, 88, 89, 146, 149, 169 Population Density, 43, 169 Posterior, 145, 146, 167, 169 Potentiating, 100, 169 Practice Guidelines, 124, 130, 169 Practice Management, 43, 170 Precursor, 154, 155, 168, 170, 176 Prevalence, 42, 57, 114, 170 Probe, 167, 170 Progression, 145, 170 Progressive, 158, 166, 170 Projection, 153, 170, 171 Promoter, 10, 18, 20, 76, 93, 170 Prophase, 166, 170 Prophylaxis, 113, 170, 176 Proportional, 155, 170 Protein Binding, 25, 170

Protein C, 81, 88, 90, 100, 101, 144, 147, 163, 170, 176 Protein S, 90, 91, 92, 106, 147, 153, 155, 157, 170 Proteinuria, 166, 170 Proteolytic, 7, 151, 170 Protozoa, 165, 170 Psychic, 171, 172 Public Health, 8, 18, 30, 32, 38, 52, 53, 106, 107, 124, 171 Public Policy, 123, 171 Publishing, 9, 171 Purifying, 80, 85, 92, 96, 171 R Radiation, 156, 171 Radiation therapy, 156, 171 Radioactive, 160, 165, 167, 171 Radioisotope, 167, 171 Randomized, 68, 154, 171 Reagent, 14, 171, 175 Receptor, 4, 5, 61, 94, 97, 143, 146, 171 Recombinant, 13, 14, 19, 37, 60, 61, 80, 89, 95, 171, 177 Recurrence, 44, 171 Red Nucleus, 146, 171 Refer, 1, 151, 156, 163, 171 Regimen, 154, 171 Remission, 171 Repressor, 167, 172 Respirator, 35, 172, 177 Respiratory Sounds, 61, 172 Retrograde, 7, 172 Rhinitis, 148, 172, 173 Ribose, 143, 172 Rickets, 41, 172 Rigidity, 162, 169, 172 Risk factor, 37, 155, 172 Rod, 146, 147, 158, 172 Rubella, 69, 105, 130 S Saliva, 15, 172 Salivary, 172 Salivary glands, 172 Schools, Medical, 4, 172 Screening, 150, 172 Sebaceous, 172, 177 Secretion, 6, 8, 17, 20, 41, 82, 100, 159, 162, 165, 172 Seizures, 82, 140, 168, 172 Sensibility, 145, 172 Sensitization, 100, 172 Septicaemia, 172, 173

Index 185

Sequencing, 87, 169, 173 Serine, 154, 173 Serologic, 14, 29, 40, 79, 160, 173 Serology, 12, 14, 19, 22, 26, 28, 173 Serotypes, 26, 173 Serum, 16, 18, 20, 30, 33, 40, 87, 145, 151, 160, 173 Shock, 82, 173 Side effect, 82, 85, 86, 92, 113, 117, 143, 173, 175 Signs and Symptoms, 171, 173 Skeletal, 173 Skeleton, 163, 173 Skull, 162, 173 Smooth muscle, 98, 145, 151, 159, 173, 174 Sneezing, 168, 173 Sodium, 81, 173 Soft tissue, 148, 173 Solvent, 156, 157, 173 Somatic, 159, 164, 173 Spasm, 99, 152, 173 Spasmodic, 81, 168, 173 Specialist, 36, 132, 174 Specificity, 20, 76, 144, 174 Spleen, 88, 164, 174 Sporadic, 36, 174 Stimulant, 159, 174 Stomach, 157, 159, 162, 168, 174 Strand, 76, 169, 174 Stress, 61, 156, 174 Subacute, 161, 174 Subclinical, 22, 161, 172, 174 Subcutaneous, 154, 157, 168, 174 Subspecies, 174 Substance P, 155, 172, 174 Substrate, 155, 174 Supplementation, 68, 174 Syncope, 27, 174 Systemic, 7, 20, 61, 83, 86, 89, 118, 148, 153, 155, 161, 171, 174, 176 T Tetani, 174 Tetanic, 174 Tetanus, 14, 17, 24, 30, 43, 60, 95, 118, 128, 129, 130, 141, 153, 174 Tetranitromethane, 89, 175 Thalamic, 146, 175 Thalamic Diseases, 146, 175 Therapeutics, 7, 118, 175 Thermal, 169, 175 Thrombin, 169, 170, 175 Thrombomodulin, 170, 175

Thrombosis, 162, 170, 175 Thymus, 71, 88, 160, 164, 175 Thyroid, 167, 168, 175, 176 Tin, 61, 169, 175 Tonic, 163, 175 Tooth Preparation, 143, 175 Toxic, iv, 5, 77, 78, 85, 88, 90, 97, 100, 102, 147, 153, 156, 160, 175, 176 Toxicity, 85, 86, 90, 94, 154, 175 Toxicology, 124, 175 Toxins, 8, 19, 76, 94, 146, 161, 165, 175 Toxoid, 18, 20, 42, 89, 95, 96, 102, 153, 176 Trace element, 175, 176 Trachea, 6, 9, 148, 163, 168, 175, 176 Transfection, 147, 176 Transfer Factor, 160, 176 Translation, 156, 176 Translocation, 156, 176 Transmitter, 143, 176 Transplantation, 160, 176 Trees, 155, 176 Tuberculosis, 152, 162, 176 Tuberculostatic, 162, 176 Tyrosine, 89, 149, 175, 176 U Ultrafiltration, 101, 158, 176 Unconscious, 153, 160, 176 Urea, 102, 176 Urinary, 150, 176 V Varicella, 130, 176 Vascular, 78, 154, 161, 166, 176 Vasodilator, 148, 159, 176 Vector, 7, 14, 80, 177 Venous, 148, 170, 177 Venous blood, 148, 177 Ventilator, 172, 177 Veterinary Medicine, 123, 177 Vibrio, 98, 150, 177 Vibrio cholerae, 150, 177 Viral, 46, 88, 97, 128, 161, 167, 177 Viral Load, 88, 177 Virulence, 5, 6, 8, 9, 11, 13, 14, 19, 21, 76, 83, 84, 86, 89, 90, 102, 113, 175, 177 Virulent, 6, 80, 92, 93, 94, 100, 177 Virus, 48, 88, 147, 157, 162, 177 Virus Replication, 88, 177 Vitro, 9, 177 Vivo, 7, 19, 21, 177 Vulgaris, 71, 177 W War, 175, 177

186 Whooping Cough

White blood cell, 88, 140, 146, 163, 164, 165, 169, 177 Whole cell vaccine, 77, 81, 82, 92, 94, 97, 100, 177 World Health, 96, 106, 141, 177 World Health Organization, 85, 96, 106, 141, 177

Wound Healing, 162, 178 X Xenograft, 145, 178 Y Yeasts, 156, 178 Z Zymogen, 170, 178

Index 187

188 Whooping Cough