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

GASTROENTERITIS 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., 1960Gastroenteritis: 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: 0-597-84434-8 1. Gastroenteritis-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 gastroenteritis. 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 GASTROENTERITIS .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Gastroenteritis .............................................................................. 7 E-Journals: PubMed Central ....................................................................................................... 45 The National Library of Medicine: PubMed ................................................................................ 50 CHAPTER 2. NUTRITION AND GASTROENTERITIS........................................................................... 59 Overview...................................................................................................................................... 59 Finding Nutrition Studies on Gastroenteritis ............................................................................. 59 Federal Resources on Nutrition ................................................................................................... 62 Additional Web Resources ........................................................................................................... 63 CHAPTER 3. DISSERTATIONS ON GASTROENTERITIS ...................................................................... 65 Overview...................................................................................................................................... 65 Dissertations on Gastroenteritis .................................................................................................. 65 Keeping Current .......................................................................................................................... 66 CHAPTER 4. PATENTS ON GASTROENTERITIS ................................................................................. 67 Overview...................................................................................................................................... 67 Patents on Gastroenteritis ........................................................................................................... 67 Patent Applications on Gastroenteritis........................................................................................ 79 Keeping Current .......................................................................................................................... 81 CHAPTER 5. BOOKS ON GASTROENTERITIS ..................................................................................... 83 Overview...................................................................................................................................... 83 Book Summaries: Federal Agencies.............................................................................................. 83 Book Summaries: Online Booksellers........................................................................................... 87 Chapters on Gastroenteritis ......................................................................................................... 88 CHAPTER 6. PERIODICALS AND NEWS ON GASTROENTERITIS ....................................................... 93 Overview...................................................................................................................................... 93 News Services and Press Releases................................................................................................ 93 Newsletter Articles ...................................................................................................................... 95 Academic Periodicals covering Gastroenteritis............................................................................ 96 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 99 Overview...................................................................................................................................... 99 NIH Guidelines............................................................................................................................ 99 NIH Databases........................................................................................................................... 101 Other Commercial Databases..................................................................................................... 103 APPENDIX B. PATIENT RESOURCES ............................................................................................... 105 Overview.................................................................................................................................... 105 Patient Guideline Sources.......................................................................................................... 105 Finding Associations.................................................................................................................. 111 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 113 Overview.................................................................................................................................... 113 Preparation................................................................................................................................. 113 Finding a Local Medical Library................................................................................................ 113 Medical Libraries in the U.S. and Canada ................................................................................. 113 ONLINE GLOSSARIES................................................................................................................ 119 Online Dictionary Directories ................................................................................................... 119 GASTROENTERITIS DICTIONARY........................................................................................ 121

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INDEX .............................................................................................................................................. 181

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and gastroenteritis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “gastroenteritis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Management of Acute Gastroenteritis in Children Source: American Family Physician. 60(9): 2555-2563. December 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: Acute gastroenteritis is a common and costly clinical problem in children. This article reviews the practical management of acute gastroenteritis in children. It is a largely self limited disease with many etiologies. The evaluation of the child with acute gastroenteritis requires a careful history and a complete physical examination to uncover other illnesses with similar presentations. Minimal laboratory testing is generally required. Treatment is primarily supportive and is directed at preventing or treating dehydration. When possible, an age appropriate diet and fluids should be

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continued. Oral rehydration therapy (ORT) using a commercial pediatric oral rehydration solution is the preferred approach to mild or moderate dehydration. The author stresses that the traditional approach using 'clear liquids' is inadequate. Severe dehydration requires the prompt restoration of intravascular volume through the intravenous administration of fluids, followed by ORT. When rehydration is achieved, an age appropriate diet should be resumed promptly. Antiemetic and antidiarrheal medications are generally not indicated and may contribute to complications. The use of antibiotics remains controversial. 7 tables. 27 references. •

Viral Agents of Gastroenteritis: Public Health Importance and Outbreak Management Source: MMWR. Morbidity and Mortality Weekly Report. 39(RR-5). April 27, 1990. Summary: Each year, infectious gastroenteritis causes more than 210,000 children in the United States to be hospitalized and 4-10 million children to die worldwide. Rotavirus, the most common cause of diarrhea among children, infects virtually every child in the United States by the age of four years and causes potentially lethal dehydration in 0.75 percent of children less than two years of age. Other recently identified pathogens include the enteric adenoviruses, calicivirus, astrovirus, and the Norwalk family of agents. Conclusive diagnosis of these viruses requires electron microscopic examination of stool specimens. Stool samples from an outbreak that are submitted to the CDC for detection of viral pathology should be collected in bulk from 10 ill persons during their first 48 hours of illness, while feces are still liquid. Acute- and convalescent-phase serum samples should be collected from the same persons, plus from an equal number of controls, during the first week of illness and three weeks thereafter. Control measures for outbreaks of viral gastroenteritis should focus on removal of an ongoing common source of infection and on the interruption of person-to-person transmission that can perpetuate an outbreak after the common source has been removed. Because improvements in environmental hygiene may not be accompanied by reductions of endemic diarrhea caused by viruses, immunization may play an important role in future control; vaccine trials for rotavirus are in progress. 68 references. (AA-M).

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Gastroenteritis in Children: Principles of Diagnosis and Treatment Source: American Family Physician. 58(8): 1769-1776. November 15, 1998. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: Gastroenteritis in children is a common reason for visits to family physicians. This article reviews common etiologies of gastroenteritis in children, appropriate assessment of hydration status, and approaches to fluid replacement. Most cases of gastroenteritis have a viral etiology and are self-limited. However, more severe or prolonged cases can result in dehydration with significant morbidity and mortality. This is often the scenario in third-world countries, where gastroenteritis results in 3 million deaths annually. A proper clinical evaluation will allow the physician to estimate the percentage of dehydration and determine appropriate therapy. In some situations, laboratory studies of blood urea nitrogen and serum electrolytes may be helpful. Stool studies are indicated if a child is having bloody diarrhea or if an unusual etiology, such as Escherichia coli O156:H7 or Cryptosporidium, is suspected. Most children with gastroenteritis can be treated with physiologically balanced oral rehydration solutions. In children who are hypovolemic (low circulating blood volume), lethargic, and estimated to be more than 5 percent dehydrated, initial treatment with intravenous

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boluses of isotonic saline or Ringer's lactate may be required. Children with severe diarrhea need nutrition to restore digestive function and, generally, food should not be withheld. 6 tables. 18 references. (AA). •

Recommendations for Collection of Laboratory Specimens Associated With Outbreaks of Gastroenteritis Source: MMWR. Morbidity and Mortality Weekly Report. 39(RR-14): 1-13. Summary: Recent discoveries have implicated a number of previously unrecognized infectious agents as important causes of outbreaks of gastroenteritis. Unfortunately, the ability to detect these agents in an outbreak can be limited by two factors: the lack of appropriate assays, many of which are still in developmental stages and are not readily available to clinical laboratories; and inadequately or improperly collected specimens. This article provides an update on guidelines and recommendations for the proper collection of specimens to be sent to the Centers for Disease Control (CDC); gives general background information concerning some recently discovered pathogens; lists some of the tests available at CDC; and provides a list of CDC contacts. The guidelines and the general information provided on causes of outbreaks of gastroenteritis can also be used by public health workers for investigations when specific testing is available and appropriate. 3 tables. 14 references. (AA-M).

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Infectious Gastroenteritis in Infants and Children Source: Gastroenterology Nursing. 14(6): 302-306. June 1992. Summary: This article discusses infectious gastroenteritis, a frequent recurring illness in young children. The author notes that gastroenteritis is caused by a viral agent in 70 to 80 percent of cases; bacteria, parasites, and toxins account for the remaining 20 to 30 percent. Topics include pathophysiology; patient evaluation; management of acute diarrhea, particularly rehydration of the child; and recovery issues including advancing the child's diet and providing good skin care. The author stresses that the care of these children focuses on accurately assessing hydration status, maintaining adequate hydration and caloric intake to promote recovery, educating the family about the infection and the treatment plan, and preventing the spread of the infection. 3 tables. 9 references. (AA-M).

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Failure of Cooking to Prevent Shellfish-Associated Viral Gastroenteritis Source: Archives of Internal Medicine. 157(1): 111-116. January 13, 1997. Summary: This article reports on a study of the largest outbreak of oyster-associated gastroenteritis ever reported (Florida, January 1995). The authors interviewed both the cohort of persons from 38 gatherings where illness was reported and a sample of harvesters and harvest area residents. Oysters were traced by means of tags and dealer records, and water quality measures in harvest areas were reviewed. The authors examined stool specimens for small round structured viruses by means of electron microscopy and amplification of RNA by reverse-transcriptase polymerase chain reaction. They also tested serum specimens for antibodies to Norwalk virus. Of 223 oyster eaters, 58 percent became ill, compared with 3 percent of nonoyster eaters. Most oyster eaters ate only cooked (grilled, stewed, or fried) oysters. Oyster eaters who reported eating only thoroughly cooked oysters were as likely to become ill as those who ate raw oysters. In 29 clusters, implicated oysters were from Apalachicola Bay, FL. A community outbreak occurred in two bayside communities before the oyster harvest, pointing to the possibility of an increase in the reportedly common practice of

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overboard dumping of feces. Results of water quality tests for fecal coliforms were within acceptable limits. The authors conclude that this large outbreak of gastroenteritis associated with oysters may have resulted from overboard dumping of feces during a community outbreak of diarrheal illness. The researchers' findings of acceptable water quality measures for fecal contamination and the lack of appreciable protective effect from cooking leave the consumer with no assurance of safety. 2 figures. 2 tables. 32 references. (AA-M). •

Rotavirus Vaccine for the Prevention of Rotavirus Gastroenteritis Among Children: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: MMWR. Morbidity and Mortality Weekly Report. 48(RR-2): 1-23. March 19, 1999. Contact: Available from Superintendent of Documents, U.S. Government Printing Office. Washington, DC 20402. (202) 512-1800. Available for free in electronic format on the World Wide Web at www.cdc.gov or from CDC's file transfer protocol server at ftp.cdc.gov. Summary: This document offers the recommendations of the Advisory Committee on Immunization Practices (ACIP) on the use of an oral, live rotavirus vaccine licensed by the Food and Drug Administration on August 31, 1998, for use among infants. The report reviews the epidemiology of rotavirus, describes the licensed rotavirus vaccine, and makes recommendations regarding its use for the routine immunization of infants in the United States. The recommendations are based on estimates of the disease burden of rotavirus gastroenteritis among children in the United States and on the results of clinical trials of the vaccine. In the United States, rotavirus is a common cause of hospitalizations, emergency room visits, and outpatient clinic visits, and is responsible for considerable health care costs. The vaccine is an oral, live preparation that should be administered to infants between the ages of 6 weeks and 1 year. The recommended schedule is a three dose series, with doses to be administered at ages 2, 4, and 6 months. Other topics covered in the report include routine administration, contraindications, precautions and special situations, managing adverse events after rotavirus vaccination, future needs, surveillance, education of health care providers and parents, and implementation. Implementation of these recommendations in the United States should prevent most physician visits for rotavirus gastroenteritis and at least two thirds of hospitalizations and deaths related to rotavirus. The report includes an inserted continuing education activity with which readers can earn 1.0 hour of Continuing Medical Education (CME) credit. 2 figures. 3 tables. 86 references.

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Bacterial and Protozoal Gastroenteritis Source: New England Journal of Medicine. 325(5): 327-340. August 1, 1991. Summary: This review article provides an update and a practical approach to the understanding, diagnosis, and management of nonviral infectious diarrhea. The authors stress that it is particularly important to understand the epidemiologic setting and pathogenesis of these infections, because they provide a clinical basis for diagnosis and management. A highly selective approach to potentially costly diagnostic tests for this common problem is imperative. The author concludes that although oral rehydration therapy is the cornerstone of treatment for all diarrheal illnesses, the severity of inflammatory and persistent diarrheas also may warrant specific antimicrobial therapy. Topics include diarrheal illness in institutional settings, travelers' diarrhea, foodborne and waterborne outbreaks, diarrhea in immunocompromised patients, enteric host

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defenses and traits of microbial virulence, the diagnostic approach, and the therapy for managing diarrheal illness. 3 figures. 3 tables. 228 references.

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

Project Title: ANIT-INFLAMMATORY EFFECTS OF HUMAN MILK Principal Investigator & Institution: Buescher, E S.; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002 Summary: This project proposes to evaluate the anti-inflammation effects of human milk feeding through free approaches: 1) Examination of human milk feeding effects and feeding of purified mil anti-inflammatory components on inflammation using animal models of inflammation; 2) in vitro studies of rat intestinal cell (target cell) and neutrophil (mediator cell) cellular responses to injury, and modulation of these responses by milk and milk anti-inflammatory components; 3) examination of the relationships between human milk content of anti-inflammatory components, urinary excretion of anti-inflammatory components by breast-fed infants and the degree of inflammation associated with illnesses in breast-fed infants. Each approach will emphasize the roles of the interleukin-1 receptor antagonist (IL-1RA) and soluble forms of the p55 and p75 TNFalpha receptors (sTNF RI and sTNF RII, respectively) in altering inflammatory responses following bowel injury (animal studies), and in the relationships between amounts fed, amounts excreted by the infant, and occurrence of illness. By defining these roles and relationships, we will establish a basis for progression to future studies examining infant feeding with formulas supplemented with anti-inflammatory components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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Project Title: BARRIER FUNCTION OF THE GI TRACT IN HEALTH AND DISEASE Principal Investigator & Institution: Walker, W Allan.; Director; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 29-SEP-2005 Summary: In this Program Project renewal reapplication, we have continued a narrowed focus to characterize the role of the enterocyte in mucosal barrier function at the interface between microbial luminal stimuli and lymphoid effector response. The enterocyte is the central focus and will be studied with regard to microbial "crosstalk," lymphoid-epithelial interactions, inappropriate developmental responses, and as a barrier to microbial penetration. The renewal application consists of five interactive projects supported by two cores, (1) an Administrative Core and (2) a Tissue Culture/Morphology/Xenograph Transplant Core principally in one location in the Mucosal Immunology/Developmental Gastroenterology Laboratories at the Massachusetts General Hospital- East. Project 1 is a new project to study the enterocyte response, in immature human fetal cells, to exo- and endotoxin. Immaturities in signal transduction responses may account for the increased incidence of age- related inflammatory disease and secretory diarrhea in human infants. Project 2 will determine the inflammatory role of mast cell cytokines and leukotrienes in response to bacterial/enterocyte interaction. Project 3 will study the mechanisms of Shigella interaction with the basolateral surface of the enterocyte interaction. Project 3 will study the mechanisms of Shigella interaction with the basolateral surface of the enterocyte at the cellular mechanisms of Shigella interaction with the basolateral surface of the enterocyte interaction. Project 3 will study the mechanisms of Shigella interaction with the basolateral surface of the enterocyte at the cellular/molecular level. Two new projects have been added to the renewal application. Project 4 will define the role of neuropeptides, specifically corticotrophin releasing factor (CRF) in the intestinal inflammatory response to Clastridial toxins and Project 5 will determine the role of tight junctions, particularly claudin cell/molecular biology, microbiology, immunology, and developmental biology will work in collaborative fashion to define microbial/epithelial responses in the context of inflammation and mucosal defenses. These studies should provide a better understanding of the pathogenesis of bacterial gastroenteritis and lead to improved ways of preventing infectious diseases of the gastrointestinal tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BOVINE SPECIFIC VIRULENCE FACTORS OF S TYPHIMURIUM Principal Investigator & Institution: Baumler, Andreas J.; Associate Professor; Medical Microbiol & Immunology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 15-JUN-1999; Project End 31-MAY-2003 Summary: (Adapted from the Applicant's Abstract): Salmonellosis is the most frequent food-borne illness in the US. The recent emergence of multiple antibiotic-resistant S. typhimurium strains, such as definitive phage type 104 (DT104) has illustrated that the use of antibiotics will no longer combat salmonellosis effectively in the future. In order to devise alternatives to antibiotic therapy for the control or prevention of Salmonella infections, an understanding of the fundamental factors that Salmonella uses to cause infection and disease is needed. Little is known about genes allowing S. typhimurium to infect cattle, an important meat source in the US. The proposed research will characterize bovine virulence factors of S. typhimurium which will facilitate the

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development of improved strategies for prevention and treatment of infection. This research will also establish a new animal model for the study of human diarrheal disease caused by Salmonella. Overall project goals and supporting objectives: (1) Analysis of the adherence mechanisms which contribute to host adaptation. (2) Analysis of the role of the invasion associated type III secretion system in host-adaptation and diarrhea. Plans to accomplish project goals: The investigators have identified two virulence factors which contribute specifically to disease in cattle. One, a putative adhesin, will be characterized to determine its role in colonization of bovine intestine. The second factor is a secretion system which is specifically required to cause diarrhea in calves. They will determine the identity of the secreted proteins and study their role in causing diarrhea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BROADLY ACTIVE INHIBITORS OF HIGH PRIORITY PATHOGENS Principal Investigator & Institution: Gulnik, Sergei; Professor; Sequoia Pharmaceuticals, Inc. 401 Professional Dr, Ste 100 Gaithersburg, Md 20879 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The recent anthrax attack of 2001 underscored the reality of large-scale aerosol bioweapons attack by terrorist groups. It also revealed that there is an urgent and pressing need to discover and develop novel and potent antimicrobials that can be used therapeutically and prophylactically for biodefense against new bioattacks. The NIH and CDC have identified a number of High Priority pathogens based on their likelihood of causing widespread contagious disease and/or death to the general population. The long range goal of this Phase I SBIR is to discover and develop potent, broad-spectrum, and mechanistically-novel antimicrobials suitable for treating and/or preventing outbreaks of diseases like anthrax, plague, cholera, gastroenteritis, multidrug-resistant tuberculosis (MDR TB), and for tackling the growing problem of antibiotic resistant bacteria strains. This Phase I application aims to generate novel inhibitors of a bacterial enzyme-3-dehydroquinate dehydratase (DHQase) using molecular target- and structure-based approaches. DHQase is a key enzyme in the shikimate pathway that is essential for the biosynthesis of aromatic amino acids in microorganisms, plants and fungi. Specific aims of the application include: 1) cloning, expression and purification of recombinant DHQases from Bacillus anthracis, Yersinia pestis, Campylobacter jejuni, Vibrio cholera and Mycobacteria tuberculosis; 2) establishing DHQase inhibitor assays using the recombinant enzymes; 3) identifying small molecule chemical leads using experimental and computational screening methods; and 4) validating binding modes of inhibitor leads using X-ray crystallography of inhibitor/enzyme complexes. High resolution crystal structures of DHQase, with and without inhibitors, are available from preliminary studies, and crystallization conditions are well established in the laboratory of the PI. The commercial goal of this SBIR is the invention of one or more patentable molecular entities with broad cross-reactivity against DHQases and the pathogens from which they are derived. Enzyme inhibitors identified in the Phase I portion of this work will serve as leads for launching into a Phase II study, the goal of which will be to translate potent and selective inhibitors of High Priority pathogens into safe and effective clinical drug candidates for use as biodefense agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAMPYLOBACTER DETERMINANTS

COLONIZATION

AND

VIRULENCE

Principal Investigator & Institution: Stintzi, Alain C.; Assistant Professor; Veterinary Pathobiology; Oklahoma State University Stillwater Stillwater, Ok 74078 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Campylobacter spp, generally food-borne, are the leading cause of gastroenteritis worldwide, surpassing the number of cases of Salmonella and Shigella combined. Campylobacter spp. are also associated with the development of Guillain-Barre syndrome, which is the most common cause of acute neuromuscular paralysis. In addition, since Campylobacter could be easily acquired and spread through our food supply, it constitutes a potential bioterrorism threat. Currently, no vaccine is available against Campylobacter infection, and despite an intensive research effort to understand Campylobacter pathophysiology, conclusions on the exact mechanism of infection are extremely difficult to draw. C. jejuni is adapted to survive both in the environment (mainly water and milk) and in its host organisms (mammals and birds). Upon entrance into the human host, Campylobacter must survive in the intestinal tract, either as a free bacterium in the mucus layer or intracellularly in gut epithelial ceils. To colonize the intestinal tract, C. jejuni must successfully transit through the gastric acid barrier of the stomach to the more alkaline environment of the intestine. While up to 500 commensal species as well as other food-borne pathogens must similarly surmount these host barriers and adapt to the gut environment, very little is known about this process. This proposal focuses on the characterization of Campylobacter jejuni colonization and virulence factors. This proposal is based on the following hypothesis: there are numerous genes expressed in rivo that are influenced by environmental factors, and several of these genes are required for gut colonization and ultimately disease development. C. jejuni colonization and virulence determinants will be identified by in vitro and in vivo survival analysis of insertional mutants using DNA microarray. First, a functional genomic tool will be developed to identify conditionally essential genes in C. jejuni, and validated to examine the mechanism of C. jejuni survival to acid stress. Second, this functional genomic tool will be used to characterize the interactions of C. jejuni with the host gastrointestinal tract using the newborn piglet as an animal model of human infection. Finally, the role of the colonization and virulence determinants in disease and Campylobacter physiology will be assessed using a battery of in vitro biological assays. The identification of these Campylobacter determinants could significantly contribute to the development of more effective methods to diagnose, manage and ultimately prevent Campylobacter infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CAMPYLOBACTER JEJUNI PROTEINS INDUCED AT 37C Principal Investigator & Institution: Thompson, Stuart A.; Assistant Professor; Biochem and Molecular Biology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Campylobacter jejuni is the leading cause of severe bacterial gastroenteritis in the U.S., and has been classified as a food-borne Category B Bioterrorism agent by the NIH. In addition to the tremendous burden of disease due to severe gastroenteritis (>2.4 million cases/yr, in the U.S.), C. jejuni infection is highly associated with the development of Guillain-Barre syndrome, an acute motor paralysis that may result from autoimmune antibodies against C. jejuni antigens. Poultry flocks are ubiquitously and asymptomatically colonized with C. jejuni, and the most probable

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route of transmission of C. jejuni to humans is probably via consumption of contaminated poultry meat. In its natural habitats, C. jejuni is able to thrive at two different temperatures, 42C (the core temperature of chickens) and 37C (in humans). Consequently, there is likely to be temperature regulation of C. jejuni proteins to facilitate the optimal expression of the subset of proteins appropriate for its current environment (i.e., poultry or humans). Using complementary microarray and proteomics approaches, we have evidence that such temperature regulation occurs. Furthermore, C. jejuni temperature regulation may increase the expression at 37C of proteins that may be important in the course of human disease, and appear to define global regulatory networks that allow the simultaneous regulation of many C. jejuni proteins. We now propose further study of temperature regulation in C. jejuni, focusing on those proteins that are induced at 37C and which may be required for C. jejuni to cause disease in humans. We will achieve these goals using the following 3 specific aims: Specific Aim 1. Using proteomics and microarray, identify and localize C. jejuni proteins that are induced at 37C, and examine interstrain variability in 37C-induced proteins. Specific Aim 2. Characterize the functions and regulation of C. jejuni proteins that are induced at 37C.Specific Aim 3. Elucidate the roles of specific 37C-induced proteins in human epithelial cell binding and invasion in vitro, and in colonization in a mouse model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL TRANSMISSION

EXPERIMENT

OF

HELICOBACTOR

PYLORI

Principal Investigator & Institution: Parsonnet, Julie; Associate Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 28-FEB-2006 Summary: (Adapted from the Applicant's Abstract): Humans are the only known reservoir of H. pylori infection. How the organism is transmitted from one person to another, however, remains unknown. Data collected during the investigators initial funding period indicate that viable H. pylori are shed by infected hosts in vomitus and diarrheal stools under conditions that simulate gastroenteritis. In addition, H. pylori infection has been linked to increased risk for diarrheal disease, specifically, symptomatic cholera and infantile diarrhea. The investigators postulate that H. pylori decreases gastric acidity, allowing gastroenteritis pathogens to circumvent the first barrier to entry into the intestine. The gastroenteritis pathogens then cause diarrhea and vomiting, fostering excretion of H. pylori and completion of the transmission cycle. With this submission, they propose: 1) to determine whether H. pylori infection, by decreasing gastric acidity, is permissive of gastrointestinal infection with acid sensitive organisms. and 2) to determine whether gastrointestinal infection which leads to diarrhea and vomiting increases shedding of H. pylori. These aims will be accomplished in a three-pronged fashion: First, they will identify suitable acid-resistant and acidsensitive strains of non-pathogenic E. coli for human inoculation, and determine the conditions for recovering these organisms from stools. Next, they will administer the acid-resistant/acid-sensitive pair to human subjects and determine the effects of H. pylori infection and gastric acidity on bacterial survival. Last, they will inoculate H. pylori infected and uninfected human subjects with low doses of an acid-sensitive, enteropathogenic E. coli (EPEC) and determine both how H. pylori affects EPEC infectivity and how EPEC affects H. pylori shedding. H. pylori infection causes gastric cancer-the second leading cause of cancer death worldwide-and peptic ulcer disease. Diarrheal disease remains a leading killer of children in developing countries, causing

12

Gastroenteritis

20 percent of infant mortality worldwide. In these same countries where diarrheal disease runs rampant, H. pylori infects up to 80 percent of the population. If a causal link between these diseases can be established, then treatment or prevention of H. pylori would attain a significantly higher public health priority than it currently occupies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL Principal Investigator & Institution: Ruiz-Palacios, Guillermo; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002 Summary: The backbone of this program project is the Clinical Site Core which unites the overall aims of the proposal: 1) to isolate, characterize, and synthesize the bioactive substances in human milk (including glycoconjugates, antibodies, and antiinflammatory factors) that protect the infant from enteropathogens; 2) to evaluate, through molecular-epidemiologic research, the protection of breast-fed infants from enteropathogens; 3) to determine, through randomized trials, the efficacy of specific bioactive substances identified in human milk to protect the infant from enteric infection and disease; and 4) to determine the effect of human milk on modulation of the immune response to enteric pathogens and vaccines. In the previous funding period of the previous application, the Clinical Site Core supported all projects. This included the sharing of demographic data and specimens, conducting field studies in Mexico (San Pedro Martir, Tlalpan) and Norfolk, specimen collection from Mexican and U.S. mothers, as well as biochemical, and biostatistical support. Field studies originating in 1987 in Mexico have enrolled in excess of 600 infants and 400 mothers. Additional studies (funded outside this project) enrolled over 600 infants in Norfolk. The Core maintained a database of all biological samples which was shared by all investigators. There have been over 2,800 milk, 1,600 blood, and 32,000 fecal samples collected, much of which has been depleted for analyses in the specific projects during 1993-8. Some of the remaining fecal samples can be used for the proposed projects, but there remain too few blood and milk samples and/or additional samples are needed to address newer aims in the current proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VOMITING

CORTICOTROPIN-RELEASING

FACTOR

ROLE

IN

CYCLIC

Principal Investigator & Institution: Li, B U.; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Cyclic vomiting syndrome (CVS) is the most severe recurrent vomiting disorder in humans and is more prevalent than previously appreciated (1 in 50 school-aged children). Although the pathogenesis remains unknown, corticotropin-releasing factor (CRF) is a tenable candidate brain-gut neuroendocrine mediator of vomiting in CVS. CRF has a well-established role in inducing gastric stasis and vomiting in animals and its resulting behavioral, autonomic, endocrine effects resemble those clinical features seen in CVS. The model of CRFinduced emeses may explain the antiemetic utility of dexamethasone during chemotherapy-induced vomiting and migraine headaches. We hypothesize that systemic CRF levels and hypothalamic-pituitary-ad renal (HPA) axis activity are heightened during episodes of CVS and migraine headache especially in those who

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experience concomitant nausea and vomiting. To provide direct clinical evidence of involvement of CRF pathways in CVS and migraine, we will examine CRF and HPA axis activation (ACTH, cortisol, catecholamines) in subjects with CVS, migraine headaches and controls under three conditions including: 1) when well (i.e. in between episodes), 2) during acute episodes of cyclic vomiting or migraine headaches treated with a saline placebo, and, 3) during acute episodes of cyclic vomiting or migraine headaches in which CRF is treated by dexamethasone. Under each condition, we will establish the diurnal variation of CRF and HPA axis activity and compare them to pediatric controls, both healthy and with non-CVS vomiting (gastroenteritis). In a randomized, double blind, cross-over design, we will examine the effect of dexamethasone on CRF and HPA axis activity, objective signs and subjective GI and migraine headache symptoms. CVS and migraine headaches may ultimately both be disorders involving dysregulation of CRF pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COW MILK ALLERGENS IN IGE AND NON-IGE MEDIATED COW MILK ALLERGY Principal Investigator & Institution: Sampson, Hugh A.; Professor; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002 Summary: Cow milk is the most common cause of food allergy in the first year of life, with approximately 2.5% of newborns experiencing allergic reactions to cow milk during this time. While most infants with non-IgE-mediated cow milk allergy [CMA] 'outgrow' their sensitivity by the 3rd year of life, 15% of infants with IgE-mediated cow milk allergy retain their sensitivity into the second decade and 35% develop allergic reactions to other foods. IgE- and non-IgE-mediated mechanisms each appear to account for about one-half of milk hypersensitivity disorders in young children. Acute urticaria and atopic dermatitis are two forms of IgE-mediated skin reactions associated with CMA. A number of distinct cow milk-induced, non-IgE-mediated skin reactions associated with CMA. A number of distinct cow milk-induced, non-IgE-mediated [presumably cell-mediated] gastrointestinal hypersensitivities have been described. Milk-induced Enterocolitis Syndrome and Allergic Eosinophilic Gastroenteritis [AEG] are well characterized clinically, but the immunopathological basis of these two disorders is poorly understood. Milk proteins have been well characterized but there is little information regarding their roles inv various milk hypersensitivity disorders. We hypothesize that differences in immune antigen-processing and presenting of specific milk proteins result in the recognition of different B cell and T cell epitopes among milkallergic patient groups and controls. We further hypothesize that patients "outgrowing" their clinical hypersensitivity will lose their ability to recognize "disease-associated epitopes". These hypotheses will be addressed 3 aims: (1) Patients with each of the well characterized CMA disorders will be recruited and followed prospectively. Both humoral and cellular responses to 4 well-characterized milk proteins will be evaluated. Cells from the peripheral blood, and skin and intestinal biopsies activated by milk proteins in vitro will be characterized as to phenotype, homing receptor positivity, and cytokine expression. (2) IgE- and IgG-binding epitopes of the 4 major milk proteins will be mapped uti9lizing sera from patients and control subjects. T cell epitopes will be established using PBMC and T-cells lines and clines established using PBMCs and will be mapped utilizing sera from patients and control subjects. T cell epitopes will be established using PBMCs and will be mapping utilizing sera from patients and control subjects. T cell epitopes will be established using PBMCs and T-cell lines and clones

14

Gastroenteritis

established from patients and controls. (3) Since approximately 50% of all milk allergic patients lose their clinical reactivity to milk in 2-3 years, patients will be followed prospectively to correlate changes n specific cells and their immunologic responses to "hypersensitivity-associated" epitopes. Characterization of distinct milk hypersensitivity reactions at a cellular and molecular level will provide new insights into the immunopathogenesis and future therapeutic strategies of food hypersensitivity disorders. This project will serve as a foundation for other projects in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISEASES

CYTOTOXIC

ENTEROTOXIN

IN

AEROMONAS-MEDIATED

Principal Investigator & Institution: Chopra, Ashok K.; Professor; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-JUL-1997; Project End 28-FEB-2007 Summary: Aeromonas is an emerging human pathogen, which causes gastroenteritis and septicemia. The organism is being isolated in increasing numbers from food and water, and is becoming resistant to chlorination in water and to multiple antibiotics. The focus of this grant is on a cytotoxic enterotoxin (Act)of Aeromonas, which, in addition to causing gastroenteritis, leads to fatal, non-intestinal infections. Based on the data generated during the current funding period, the following specific aims will be addressed. In Aim 1, we will identify a protein/glycoprotein receptor, which appears to be attached to the plasma membrane by a GPI-anchored protein on the intestinal epithelial cell line (T84), to which Act binds, to initiate a signal transduction cascade. These studies will be accomplished by photoaffinity labeling the receptor with Act, by a genetic approach based on a yeast two-hybrid system, and/or by surface plasmon resonance. In Aim 2, we will delineate the signal transduction cascade triggered by binding of Act to its cell surface receptor on the host cell to better understand the mechanism of action of Act. These studies will involve examining the effect of calcium mobilization and oxidative-stress pathways on TNFalpha and PGE2 production in Actstimulated cells. In Aim 3, the intracellular trafficking of Act in the host cell will be examined by using specific inhibitors and the mutated Rab proteins using immunofluorescence/confocal microscopy, and we will study stress-associated protein kinase activation by Act from within the host cell. For these studies, Act will be delivered into T84 cells via lipofection or electroporation to prevent receptor-mediated signaling. In Aim 4, we will dissect the role of various mediators generated via Act signaling that lead to different biological effects of Act. We will specifically examine mechanism of Act-induced apoptosis in macrophages via caspase 9 and the role of various biological mediators in fluid secretion, using both in vitro and in vivo models. These studies will provide valuable information in intervening in the severe pathological sequelae associated with Aeromonas infections in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION OF PATHOGENS IN AVIAN FECAL POLLUTION Principal Investigator & Institution: Mclellan, Sandra L.; Assistant Scientist; None; University of Wisconsin Milwaukee Box 413, 2200 Kenwood Blvd Milwaukee, Wi 53201 Timing: Fiscal Year 2003; Project Start 11-JUL-2003; Project End 10-JUL-2005 Summary: (provided by applicant): Nationwide, beach closings constitute a major environmental and public health concern. Recreational water quality is evaluated by

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measuring levels of bacteria such as enterococci, fecal coliforms, or E. coli, all of which indicate the presence of fecal contamination. In freshwater, the EPA recommends that water quality advisories be issued when levels exceed the guideline of 235 E. coli/100 ml; these levels have been established by epidemiological studies that have shown a correlation between concentrations of indicator organisms and gastroenteritis. The health risks associated with exposure to fecal pollution are different depending on the source of contamination. We have found that levels of E. coli in recreational water are highly influenced by localized contamination from roosting birds, and many times are not a reflection of serious contamination events that present a known health risk, such as human sewage overflows. Gulls, the most prevalent type of coastal aquatic bird and waterfowl, are known to carry human pathogens such as Salmonella and Campylobacter. The potential for beach areas to act as reservoirs for human pathogens is not known. In addition, the relationship between levels of human pathogens introduced into surface water by gulls or waterfowl and those of indicator bacteria is not well established. We will evaluate human health risk at beach sites that have experienced chronic beach closings due to localized contamination. In these studies we will 1) determine pathogen occurrence in gull populations that inhabit beach areas, 2) develop direct detection methodology for pathogens that can be applied to recreational water samples, and 3) perform pilot studies to determine the potential for avian adenovirus to be used as a specific marker for avian fecal pollution. Basic information as to the occurrence of human pathogens in beach ecosystems is essential in order to design further studies to assess human health risk, determine parameters that influence transport and fate of these pathogens in the nearshore environment, and finally, develop assessment tools that can discern the sources of fecal pollution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISCOVERY MICROARRAYS.

OF

SALMONELLA

SIGNATURE

SNPS

BY

Principal Investigator & Institution: Sparks, Andrew B.; Perlegen Sciences, Inc. 2021 Stierlin Ct Mountain View, Ca 94043 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): To meet the challenge of bio-terrorism, pathogen genome sequencing with a view to the development of new reagents and applications is a high priority of NIAID. Salmonella is a NIAID Category B pathogen. Worldwide, Salmonella typhi is responsible for 16 million cases of typhoid fever and 600,000 deaths annually. Previous Samonella outbreaks in the United States have resulted from the deliberate anthropogenic introduction of Salmonella typhi to cause typhoid fever and Salmonella typhimurium to cause gastroenteritis. The goal of this research is to identify polymorphic loci in Salmonella to enable rapid and accurate identification of Salmonella subspecies and strains. To this end, we will use high-density oligonucleotide microarray (HDOMA) technology to re-sequence the genomes (and associated plasmids) of 44 representative strains of Salmonella, including 15 strains of S. typhi, 15 strains of S. typhimurium, two strains each of S. enterica subspecies II, IlIa, IIIb, IV, VI, and VII, and two strains of S. bongori. We will then develop and employ a Salmonella genotyping HDOMA to characterize 8000 polymorphic loci we discover in the resequencing phase in a total of 130 strains of Salmonella, including the strains discussed above plus 30 additional strains of S. enterica subspecies I; 8 additional strains each of S. enterica subspecies II, IlIa, IIIb, IV, VI, and VII; and 8 additional strains of S. bongori. These data will be used to establish a Salmonella comparative genome sequence resource containing the strain resequencing data and a Salmonella genotype database containing the strain

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Gastroenteritis

genotype data. These resources should prove useful in characterizing the epidemiology of Salmonella outbreaks. Successful application of HDOMA-based polymorphism discovery in this study could be extended to characterizing variation in other sequenced microbial pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENHANCING THE IMMUNOGENICITY OF HUMAN ROTAVIRUS VACCINES Principal Investigator & Institution: Saif, Linda J.; Professor; Food Animal Hlth Research Prog; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 30-SEP-1992; Project End 31-DEC-2006 Summary: (provided by applicant): Rotaviruses (RV) are the leading cause of severe gastroenteritis in infants and children worldwide. The RV genome consists of 11 segments of dsRNA which encode 6 structural (VP) and 6 non-structural (NSP) viral proteins. The diversity and complexity of RV antigens (outer capsid VP4, VP7, and NSP4 sero/genotypes) have hindered identification of the determinants of protective immunity. Both the complexity of RV and the need to induce intestinal immunity in infants have impeded development of effective RV vaccines. Because the exact nature and extent of cross-protection to RV serotypes is not clearly characterized, there is little consensus among researchers on the necessity for pursuing monovalent versus multivalent RV vaccines. The goal of our proposed studies is to improve our understanding of the immunological mechanisms of heterotypic compared to homotypic protective immunity and to identify the correlates of immunity for heterotypic protection. We will extend our studies of the neonatal gnotobiotic pig model of homotypic HRV infection and disease to determine the extent and mechanisms of cross-protective immunity between two distinct VP7(G) types, G1 (Wa, P1AG1) and G3 (M, P1AG3), the two most prevalent human RV (HRV) G serotypes identified in many epidemiologic surveys. A variety of virus-like particles (VLPs) which are antigenically similar to native double (2/6VLP) or triple (2/4/6/7VLP) layered RV particles but noninfectious will allow us to dissect the contributions of VP4, VP6, or NSP4 from those of VP7 in heterotypic (G type) protective immunity. Our specific aims are as follows. 1) To investigate the role of replicating versus non-replicating vaccines and the effect of vaccine routes (oral versus intranasal, IN) to prime neonatal mucosal immune responses and to induce protection. We will examine whether IN or oral 2/4/6/7VLPs can substitute for oral attenuated HRV in priming for protective immunity with 2/6VLP boosters and homotypic virulent HRV challenge. We will explore the mechanisms of VLP booster responses by in vivo and in vitro boosting of primed lymphocytes with VLPs. To test the effect of route, adjuvant, and preexisting immunity on vaccine uptake, we will investigate the uptake of green-fluorescent fusion protein-2/6VLP given orally or IN with or without immune stimulating complexes adjuvant (ISCOM, used for all VLPs) in naive versus 2/6VLP primed pigs. 2) To investigate the role of VP6 in heterotypic protection, we will compare immune responses and protection rates between pigs primed with G1 or G3 VLP or attenuated HRV vaccines and boosted with 2/6VLPs or 2/4/6/7VLPs and then challenged with virulent G3 or G1 HRV. 3) To determine the role of VP7 in heterotypic protection, we will add VP7 to the 2/6VLP booster vaccines (in the form of 2/6/7VLPs) to examine how repeated exposure to VP7 (without VP4) contributes to the immune responses to heterotypic HRV and protection. 4) To examine the role of VP4 in heterotypic immunity, we will compare VLP vaccines with or without VP4. Because Wa and M HRV share the same VP4 type, the contribution of VP4 in homotypic or heterotypic (G type) protection can be dissected from that of

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VP6 and VP7. 5) To examine the role of NSP4 in enhancing homotypic and heterotypic protection, we will evaluate if addition of NSP4 (in NSP4-VLPs) as booster vaccines enhances the immune responses and increases the protection rates to homotypic RV challenge or broadens the protection rates to heterotypic RV challenge. Immune responses (HRV-specific, RV-protein-specific, and memory T and B cells and antibodies, serotype-specific virus neutralizing antibodies, and cytokine profiles) will be quantitated in intestinal, tonsillar, and systemic lymphoid tissues using ELISPOT, LPA, FACS, neutralization tests, and ELISA. A better understanding of the mechanism of induction of heterotypic immunity to RV will facilitate the development of effective and safe vaccination strategies to confer consistent protection in the face of HRV infection by the major serotypes prevalent worldwide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENVIRONMENTAL CHANGE AND DIARRHEAL DISEASE Principal Investigator & Institution: Eisenberg, Joseph Ns.; Environmental Health Sciences; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Diarrheal diseases are predictable outcomes when fecal-oral pathogens meet human poverty and-dislocation. Are diarrheal diseases sensitive indicators of change in socioeconomic level, resource availability, and human social contacts? Processes like these are extremely difficult to study in a controlled fashion. The construction of a new road in coastal Ecuador provides a valuable natural experiment for this purpose. This road will link some previously remote villages to local, regional, and national networks of goods, services, and people, creating new connections among them. We hypothesize that: (1) the level and type of connections between villages are correlated with infection of enteric pathogens; and (2) the changing social connections, new resources, and sanitary and hygienic behaviors of individuals within villages are correlated with infection of enteric pathogens. These hypotheses use the village as their unit of analysis. When estimating the contribution of various exposure risks to disease incidence, it is also important to explore the implications of interdependence between these pathways. This is the third aim of our study: analyzing the joint effects of changes in these contact patterns using disease transmission models. Using a quasi-experimental design, twenty villages will be followed for 4 years, selected so that a rural-urban continuum is fully represented. This continuum will be measured by several factors that relate a given village to Borbon, the town located at the confluence of two rivers that support the villages within the region. Data will be collected at three levels. First, health promoters who live in the villages under study will implement an active surveillance program. They will administer a new survey tool to measure the incidence of all the diarrheal illnesses and monitor both proximal and distal determinants of disease, in a given village. Second, a biannual visit to each community will be conducted by our field team, which has recently completed a cross sectional feasibility study in these villages. Each visit will last two weeks. In these visits, stool samples will be collected from all symptomatic individuals and a random selection of controls. In addition, during these visits, survey tools will be used to collect information on water-use behavior sanitation, hygiene, food consumption patterns, and travel and migration. Third, semi-annual visits to each village will be undertaken by the local Ecuadorian anthropologist. These visits will include open-ended interviews as well as additional questions about social network formation and change. The visits will also allow village development and road. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Gastroenteritis

Project Title: ESCHERICHIA COLI STABLE ENTEROTOXIN Principal Investigator & Institution: Newburg, David S.; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002 Summary: Enterotoxigenic E. coli that produce heat labile (LT) and heat stable (ST) enterotoxins are a major cause of enteric disease in many areas of the world. We have found that ST is inhibited by human milk in vitro and in vivo. All of this inhibition resides in the ST inhibitory fucosyloligosaccharide (STIF). The oligosaccharide binds to the extracellular domain of guanylyl cyclase, thereby inhibiting binding of ST. The protective oligosaccharide is a large structure present in too low a concentration to be routinely measured directly by HPLC and the molecule is too large to be synthesized routinely. However, its concentration in milk may be inferred by measuring small, more plentiful, structurally homologous oligosaccharides or might be measured directly by a solid phase assay. We hypothesize that the activity of STIF resides in the fucose containing moieties at the non-reducing terminus of the molecule and, thus, can be mimicked by structurally homologous compounds. Thus, the following aims are proposed: Determine the three-dimensional conformation of the ST inhibitory fucosyloligosaccharide. Chemically synthesize STIF, as well as a series of STIF homologs designed to incorporate or approximate structural features of the natural compound to define the minimum structure necessary for activity. Search for natural homologs and analogs to STIF from milk of other species. Utilize pure STIF homolog or analog to study details of the inhibition of ST-induced transmembrane signaling. Investigate the survival of STIF oligosaccharide structure and biological activity after transit through the gastrointestinal tract of the infant. Assess the clinical relevance of STIF levels in human milk. Test the safety, tolerance and efficacy of STIF or its analogs in prevention or ameliorating ST-related enteric disease in a population of Mexican infants at high risk for ST-related disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC COLONIZATION

ANALYSIS

OF

CAMPYLOBACTER

JEJUNI

Principal Investigator & Institution: Hendrixson, David R.; Laboratory Animal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-2002 Summary: (provided by applicant): Campylobacter jejuni is the leading cause of bacterial gastroenteritis in developed countries and a major cause of bacterial diarrhea throughout the world. The gastrointestinal tracts of many birds serve as a natural reservoir for the bacterium and humans most often come into contact with the organism by consuming contaminated chicken meats. Despite the prevalence of C. jejuni in human disease, our understanding of pathogenic mechanisms and virulence factors of the bacterium is sparse compared to other enteric pathogens. This lack of knowledge is mainly due to the relative scarcity of available genetic tools to study the organism. We have developed a system of random transposon mutagenesis for C. jejuni and used the derived isogenic mutants to identify genes required for flagellar motility, including carB and carC (encoding proteins with homology to bacterial chemotaxis proteins and the aerotaxis receptor of E. coli, respectively) and rpoN (encoding sigma 54). The aims in this proposal are to understand the roles of the Car proteins and sigma 54 in C. jejuni motility, a phenotype required for efficient colonization of chickens. In addition, we will

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modify the transposon and perform signature-tagged mutagenesis in C. jejuni to identify genes required for chicken colonization. This last aim will allow us to begin to understand requirements of C. jejuni for colonization of a natural host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF SURVIVAL OF YERSINIA PSEUDOTUBERCULOSIS Principal Investigator & Institution: Mecsas, Joan C.; Assistant Professor; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: (provided by the applicant): Yersinia pseudotuberculosis is a gram-negative, enteric bacterial pathogen that causes gastroenteritis, mesenteric lymphadenitis, which can be misdiagnosed as appendicitis leading to unnecessary surgery, and occasionally systemic disease in humans and other mammals. To cause these syndromes, the bacteria colonizes a variety of tissues in a mammal, including the lumen throughout the gastrointestinal tract (GI), the Peyers patches, mesenteric lymph nodes, and eventually the spleen and liver. Colonization of each of these tissues requires expression of at least one or more of the Yersinia virulence factors, called Yops. The Yops, which are found in all three pathogenic Yersinia spp. and share homology to virulence factors in other bacterial pathogens, are secreted into host cells via a type III secretion machinery where they disrupt properties of mammalian cells. Most Yops, studied to date, have several phenotypes in cells in culture and/or multiple protein targets in biochemical assays. The long-term goals of this project are to understand the bacterial factors needed to establish an infection in specific tissues and the host defense mechanisms targeted by bacterial virulence factors. The specific goals of this proposal are to characterize which Yops are important in the GI tract and lymph tissues, which cell culture and/or biochemical phenotypes of the required Yops are needed for colonization in the GI tract and lymph, and to characterize the host defense factors in the 01 tract that combat a Yersinia infection. This work has the potential to uncover heretofore-unknown aspects of host defense mechanisms in the GI tract. In addition, studies of yop mutant Yersinia strains in mouse strains with specific immune defects may indicate the facets of the immune system targeted by each Yop. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF T HE ROTAVIRUSES Principal Investigator & Institution: Ramig, Robert F.; Professor; Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1984; Project End 29-FEB-2004 Summary: This proposal continues to use genetic, biochemical and molecular biological approaches to study the fundamental genetics, biology, and pathogenesis of the rotaviruses; a group of viruses that are the major cause of gastroenteritis in children and the young of other species. The studies focus on three broad areas: [i] fundamental genetics of the rotaviruses, [ii] studies relating to virus structure including visualization of protein interactions in reconstructions of virus particles and studies to identify specific domains of viral proteins that interact in virus particles, and [iii] studies of pathogenesis with special emphasis on infection at peripheral sites. The results of these studies will enhance the understanding of mechanisms of interaction between enteric viruses and the host, may reveal unique pathways characteristic of rotavirus infection, and will provide information potentially useful in development of vaccine control strategies and antiviral drugs. Three specific aims are proposed: (1) Genetic analysis of

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rotaviruses. Mutants will be mapped by complementation of unmapped ts mutant groups in cells expressing wild type proteins, mutations in structural genes will be finemapped by sequencing, and the biochemistry of infection with the mutants will be characterized. (2) Studies on assembly and morphology of infectious virus particles. Cryoelectron microscopy and computer-assisted reconstructions will be used to understand structural changes associated with activation of viral infectivity by protease cleavage of VP4, structural changes in reassortants with altered interactions among structural proteins, and to visualize actively replicating template RNA in replicase particles. Domains of structural proteins that interact in the virion will be further characterized by a combination of genetic, biochemical, and functional assays. (3) Studies of rotavirus pathogenesis and virulence. Studies will be continued to examine rotavirus infection of the liver including, identification of the block to replication of some virus strains in liver cells, identification of genes governing escape of virus from the gut to infect peripheral sites, and identify mutant genes and specific mutations in viruses adapted to grow in liver cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOSPITAL-BASED ASSESSMENT OF HUMAN ASTROVIRUS INFECTION Principal Investigator & Institution: Mitchell, Douglas K.; Pediatrics; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2003; Project Start 15-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant) This research will be done primarily in Pecs, Hungary in collaboration with Dr. Gyorgy Szucs as an extension of NIH grant # RO1 AI4587-02 entitled "Moleculary Epidemiology and impact of human astroviruses". Astroviruses cause 2-17% of the diarrhea episodes that require medical care in children. Acute infectious gastroenteritis is one of the most important diseases in Hungary. A nationwide surveillance (1999) identified approximately 50,000 gastroenteritis episodes annually in the 10 million population of Hungary of which 52% were non-bacterial episodes. Of the non-bacterial gastroenteritis, 34% occur in children younger than 5 years of age. The parent grant focuses on the impact of human astroviruses (HastVs) among hospitalized children in a developed country (U.S.) and a community study among children in a developing country (Mexico). This study intends to characterize HAstVs in an Eastern European population (Hungary). Very little is known about HAstVs in this region. Active surveillance and the utilization of molecular epidemiology techniques developed in the parent grant for characterization of HAstVs should generate new understanding and possibly new reagents for the detection of HAstVs. This grant will infuse new methods, capabilities, and funding for research into an already productive collaboration. The hypotheses of this study are that HAstVs are a significant cause of acute gastroenteritis among children in Hungary and that clinical outcome in the country differs by genetic and/or antgenic types. The specific aims of this study are: 1. To determine frequency and genetic variability of HAstV strains among children hospitalized for gastroenteritis in Pecs, Hungary. 2. To determine the clinical characteristics of HAstV infection in children hospitalized for gastroenteritis in Hungary. 3. To measure the level of serum antibody in acute blood samples of children from symptomatic infections to determine the seroprevalence of HAstV type-specific antibodies. 4. To determine the burden of gastroenteritis associated with HAstV infection by evaluating the economic impact of severe HAstV diarrhea among children in one hospital over two years of surveillance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOST FACTORS MEDIATE INVASION BY CAMPYLOBACTER JEJUNI Principal Investigator & Institution: Mansfield, Linda S.; Professor; Large Animal Clinical Sciences; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-DEC-1997; Project End 30-NOV-2002 Summary: (Adapted from the applicant's abstract): Campylobacter jejuni is the leading cause of intestinal infection in humans in the US and the world, and has been designated as an emerging disease by the US CDC. This bacterium opportunistically invades the gastrointestinal tract, especially the colon, causing gastroenteritis, proctitis, and occasionally other problems, but the factors controlling this invasion are largely unknown. Long-range goal: to understand the mechanisms of resistance to opportunistic invasion of the gastrointestinal tract by C. jejuni; to provide a new animal model for testing cytokine and vaccine therapies for C. jejuni disease in humans. The proposal is based on the investigators previous work with a swine model wherein subsequent to intestinal infection with Trichuris suis, C. jejuni invades the swine colon. Mechanisms of resistance to mucosal invasion by C. jejuni are unknown. The objective is to determine the mechanism whereby T. suis facilitates the invasion of host cells by C. jejuni in piglet colons. The hypothesis to be tested is that T. suis allows C. jejuni to invade 1) by acting directly on cells with a secreted mediator to facilitate uptake of C. jejuni, or 2) acting indirectly through stereotypic immune or proinflammatory responses to downregulate resistance of host cells to C. jejuni invasion. Specific Aims: 1) Determine what cell types are invaded by C. jejuni in T. suis induced C. jejuni infections in swine, 2) Determine whether serotype cytokine patterns are associated with C. jejuni invasion of host cells, 3) Determine whether C. jejuni invasion is facilitated due to a direct effect of some secreted/excreted product of the worms, and 4) Determine what host cell genes are differentially expressed during C. jejuni invasion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE MECHANSIMS OF ROTAVIRUS PROTECTION & CLEARANACE Principal Investigator & Institution: Blutt, Sarah E.; Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-2002 Summary: Rotavirus is the leading cause of severe gastroenteritis in young children worldwide. A vaccine to prevent a rotavirus infection would prevent over 500,000 deaths/year in developing countries and save the United States over $1 billion a year in health care costs, but recently, the only licensed vaccine was withdrawn due to associated side effects. Protection from rotavirus infection and resulting disease is dependent on the initiation and maintenance of an immunological response. The goal of this application is to understand and compare the difference in protective immunological responses induced by a live rotavirus infection and by a non-replicating subunit vaccine (VLPs). The immunological response to both live rotavirus infection and a VLP vaccine will be differentiated by many factors including the time of response, the type of cells that control the response, and establishment of immunological memory. In mice, rotavirus infection and VLP vaccination can induce sterilizing immunity. The exact mechanisms through which rotavirus and VLPs induce sterilizing immunity in the mouse have not been elicited. I hypothesize that (i) clearance of and sterilizing immunity established by a primary rotavirus infection occurs predominately as a result

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of T cell independent B lymphocyte activation, and (ii) VLP vaccination will cause sterilizing immunity through T cell dependent B lymphocyte activation. To test this hypothesis, flow cytometry will be used to identify, quantitate, and functionally characterize activated lymphocyte subsets during clearance of a primary rotavirus infection, after vaccination with VLPs, and after a rotavirus challenge of previously infected or VLP vaccinated mice. These will be the first studies to systematically identify and compare subsets of activated lymphocytes between a live infected and VLP vaccinated animal and correlating these responses with protection from infection. Understanding the mechanisms of how rotavirus and vaccination with VLPs activate the immune system to induce sterilizing immunity will aid in better vaccine design and may identify benchmarks for testing potential vaccine effectiveness in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNITY AND PATHOGENESIS OF A NOVEL CALICIVIRUS Principal Investigator & Institution: Virgin, Herbert W.; Associate Professor; Pathology and Immunology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): We have discovered the first murine calicivirus, which we have designated Mouse Calicivirus 1 or MCV 1. An important and unique property of MCV 1 is that it infects and causes disease in laboratory mice, thereby presenting the opportunity to study calicivirus pathogenesis and immunity in a well characterized small animal model. Human caliciviruses such as Norwalk virus are major causes of epidemic gastroenteritis in adults, and thereby cause significant morbidity and economic loss. Studies of caliciviruses in cats and pigs have led to important advances in the understanding of calicivirus biology and pathogenesis. However, basic questions regarding virulence determinants, cell tropism, and mechanisms of immunity remain unanswered. Moreover, and important to human health, it is not known whether it is possible to effectively vaccinate against these agents, and mechanisms of vaccination are undefined. Thus, the lack of a small animal model with extensive genetic and immunologic tools for the analysis of pathogenesis and immunity has held back research on these important viruses. The discovery of MCV 1 thereby affords new opportunities for basic research into calicivirus virology and immunology. To date we have sequenced the new virus and found that it is in the Norwalk-like genus of caliciviruses, shown that gradient purified virus induces disease, expressed the capsid protein in baculovirus and shown that it assembles into virus like particles (VLPs), shown that the virus replicates in various tissues and is shed in stools after intranasal, peroral, or intracranial inoculation, and shown that (surprisingly) the virus does not kill T and B cell deficient mice but does kill mice deficient in STAT1 or interferon (IFN) receptors. Based on these results we propose to pursue the following Aims. Aim 1. Characterize MCVl and develop a reverse genetic system for MCV1. Aim 2. Determine the role of the innate immune response in control of MCV1 infection. Aim 3. Determine the role of the adaptive immune response in clearance of, and vaccination against, MCV1 infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VACCINES

INDO-US

COLLABORATION

TO

DEVELOP

ROTAVIRUS

Principal Investigator & Institution: Bhan, Maharaj K.; All-India Institute of Medical Sciences Ansari Nagar New Delhi,

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Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2008 Summary: Rotavirus infects all children by 5 years of life, and is the most common cause of severe gastroenteritis worldwide. In the US, rotavirus is a common cause of morbidity, accounting for considerable health-care costs. However, morbidity and mortality are most serious in developing countries. Disease burden studies have established rotavirus as an important cause of diarrhea and death in Indian children. In India, rotavirus is responsible for about 20% of diarrhea related hospitalizations and 100,000 deaths; the annual number ofrotavirus specific hospitalizations is approximately 500,000. First rotavirus infections are associated with the most severe diarrhea, but natural immunity protects against severe diarrhea upon reinfection. Live, oral vaccines protect against severe rotavirus diarrhea of infancy, and several rotavirus vaccines have been developed. The only rotavirus vaccine licensed to date - an oral, live, tetravalent, rhesus-based vaccine -was found to be safe and efficacious in clinical trials. However, it was subsequently withdrawn from the US market because of an increased incidence of intussusception among vaccine recipients. A rotavirus vaccine program is still needed to prevent the global burden of rotavirus associated morbidity and mortality. This is a high priority in developing countries leading to investigation of other vaccines. The proposed study will investigate two live, oral rotavirus candidate vaccines, strains 116E and I321, for prevention of severe rotavirus diarrhea in Indian children. Development of the vaccine strains is based on molecular and epidemiologic evidence that they are naturally occurring human bovine reassortants, circulating in India, with favorable clinical and immunologic profiles. Each of the Indian strains is genotypically distinct and there is no way to determine to superiority of either without conducting the proposed clinical trials. Both will be tested in parallel to define the most viable vaccine candidate (e.g., higher cactogenicity, poor immunogenicity, low efficacy, low yield). Collaborative efforts by investigators at AIIMS (India), IISc (India), Stanford University and CDC are proposed to conduct Phase I, II and [II clinical studies of the Indian strains among Indian infants. This collaboration will provide capacity-building for a vaccine testing and evaluation center at AIIMS. The opportunity to understand host and pathogen-associated factors related to pathogenesis of intussusception is also available through this collaboration. The proposed studies will support future efforts towards vaccine development in India as well as to understanding of adverse events associated with live, oral vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDUCTION OF MACROPHAGE INOS BY SALMONELLA Principal Investigator & Institution: Cherayil, Bobby J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): Various serotypes of the enteric Gram-negative bacterial pathogen Salmonella are responsible for a number of diseases of public health significance, including acute gastroenteritis, as well as typhoid fever. During the course of infection, these organisms invade intestinal epithelial cells, dendritic cells and macrophages of the host. In doing so, the bacteria introduce specific effector proteins into the host cells through a specialized secretory apparatus. The cytoskeletal changes and activation of cellular signaling pathways induced by these proteins facilitate bacterial invasion and also elicit the production of host pro-inflammatory molecules. Elucidating exactly how the effector proteins carry out these functions would help to clarify the pathogenesis of, and might suggest new approaches to treating, Salmonella associated disease. In preliminary experiments, I have found that the effector SopE2, a guanine nucleotide exchange factor for mammalian Rho GTPases, is necessary for the

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Salmonella -dependent upregulation of inducible nitric oxide synthase (iNOS), the enzyme that is responsible for controlling the production of nitric oxide (NO) in macrophages. The pro-inflammatory and immunomodulatory effects of NO contribute to anti-microbial defense, as well as to the tissue damage that is associated with infection. In further studies, I have found that SopE2 activates the transcription factor NF-kappa-B, both on its own, and in a synergistic interaction with TRAF6, an adaptor molecule involved in signaling via members of the Toll-like receptor, and TNF receptor families. The experiments proposed in this application will extend these preliminary observations to elucidate the function of SopE2, and its homolog SopE, by (a) examining the mechanism by which SopE2 and SopE initiate signals leading to iNOS induction, particularly the role of the Rho GTPases in this process (b) elucidating how SopE2 and SopE activate NF-kappa-B, and characterizing their influence on TRAF-dependent signals, (c) identifying cis-acting transcriptional regulatory elements in the iNOS promoter that respond to Salmonella infection, and to Sop-induced signals, and (d) examining the role of SopE2 and SopE in iNOS induction by Salmonella in primary macrophages and dendritic cells. The results of these studies will shed light on a novel function of SopE and SopE2 and will also improve understanding of the mechanisms that regulate iNOS expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTESTINAL INFLAMMATION ORCHESTRATED BY PATHOGENS Principal Investigator & Institution: Mc Cormick, Beth A.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: The active phase of both Salmonella-associated gastroenteritis and chronic states of inflammatory bowel disease IBD), such as ulcerative colitis and Crohn's disease, is characterized histologically by polymorphonuclear leukocyte (PMN) migration into and across the epithelial lining of the intestine. These events result in acute inflammation of the epithelium and subsequent epithelial dysfunction. The degree of PMN transmigration into intestinal crypts and the formation of crypt abscesses is indicative of disease severity and is used clinically to evaluate the activity of IBD. It is unclear what triggers directional movement of PMN across the intestinal epithelium. Towards this end, we have recently shown that epithelial cells themselves can send such signals to underlying PMN and these signals are regulated by enteric flora, such as S. typhimurium. The broad long term objectives of this proposal are to investigate the molecular mechanism by which epithelial cells in response to microbial pathogens can signal to PMN and orchestrate their directed migration. Once we begin to understand the basis of such transcellular signaling important in promoting disease flares of S. typhimurium pathogenesis, it may be possible to develop novel therapeutic strategies aimed at treatments for and ameliorating IBD. The specific aims are ultimately directed at achieving this goal, and are three-fold. Specific Aim 1 is designed to determine the nature of S. typhimurium virulence factors and define their contribution to the epithelial orchestration of mucosal inflammation. Specifically, we will delineate how S. typhimurium SipA, SopB, and SopA secreted proteins interfere with the signaling pathways which lead to epithelial orchestration of mucosal inflammation by expression of these proteins in epithelial cells using adenoviral expression vectors. Functional effect of expression of these proteins on orchestration of proinflammatory events which govern PMN transepithelial migration will be correlated with morphological consequences by both confocal and electron microscopy. Specific Aim 2 is designed to identify the signal transduction cascades which lead to the release of the

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proinflammatory chemoattractant PEEC and will employ several different approaches which include determining the relationship between S. typhimurium invasion and the apical epithelial release of PEEC, examination of the role of the JNK-pathway, determining the effects of small GTPase (cdc42, rac-1, and Arf6) expression on the ability of S. Typhimurium to induce PMN transepithelial migration by expression of dominant inhibitory mutants using adenoviral expression vectors, examining the role of phosphinositide signaling, and determining whether the ability of S. typhimurium to elicit PEEC secretion correlates with their ability to induce an increase in intracellular calcium in model intestinal epithelia. Specific Aim 3 is designed to characterize a recently identified pro-inflammatory PMN chemoattractant. The first part of this aim will elucidate the structure of PEEC utilizing HPLC purification, NMR analysis, mass spectrometry and sequence analysis, while the second part of this aim will define PEEC's relationship to other PMN chemoattractants including its ranking in the PMN chemoattractant hierarchy, will determine whether PEEC is able to activate other immune-type cells as well as assess the role of PEEC in inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ANTIBIOTIC EFFLUX IN CAMPYLOBACTER Principal Investigator & Institution: Zhang, Qijing; Vet Microbiol & Prev Medicine; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Campylobacter jejuni, an important foodborne pathogen causing gastroenteritis in humans, has evolved multiple mechanisms to counteract the action of various antibiotics, which has posed a serious threat to public health, Many of these resistance mechanisms, such as gyrA mutations and betalactamase production, confer Campylobacter resistance to specific antibiotics. However, the active efflux systems, which extrude structurally diverse antibiotics out of bacterial cells, contribute to the intrinsic and acquired resistance to multiple drugs. Although previous studies suggested the possible presence of functional efflux systems m C. jejuni, the antibiotic efflux machinery in this pathogen has not been defined. Using transposon mutagenesis in conjunction with other approaches, we have recently characterized a three-gene operon (named cmeABC) encoding a tripartite antibiotic efflux pump that contributes to C. jejuni resistance to structurally unrelated antibiotics, heavy metals, bile salts, and other toxic compounds. Our preliminary data and the genomic sequence of C. jejuni NCTC 11168 suggested the presence of an additional antibiotic efflux system (name cmeDEF) and the possible regulation of cmeABC and cmeDEF by transcriptional repressors. Based on these observations and the known features of bacterial antibiotic efflux systems, we hypothesize that CmeDEF in conjunction with CmeABC plays an important role in extruding various agents, and the modulated expression of the efflux pumps by regulatory proteins contributes significantly to the intrinsic and acquired resistance of Campylobacter to multiple antimicrobials. To test our hypothesis, we plan to i) determine the role of CmeDEF and its interplay with CmeABC in mediating Campylobacter resistance to multiple drugs and ii) to identify and characterize the transcriptional repressors that modulate the expression of the antibiotic efflux systems. Various genetic and biochemical approaches, including random and site-specific mutagenesis, recombinant proteins, substrate accumulation assay, and DNA binding assays will be utilized to define the functions of the efflux systems and their interplay with regulatory proteins. It is anticipated that the proposed studies will close a major gap in our understanding of the antibiotic resistance

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mechanisms in C. jejuni and may open new avenues for the design of effective means to prevent and treat antibiotics-resistant Campylobacter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CORONAVIRUS RNA AMPLIFICATION Principal Investigator & Institution: Brian, David A.; Professor; Pathobiology; University of Tennessee Knoxville Knoxville, Tn 37996 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 31-MAY-2007 Summary: (provided by applicant): Coronavirus-induced diseases in humans and animals are widespread and include acute respiratory disease, gastroenteritis, hepatitis, nephritis, and acute and chronic encephalitis. This proposal seeks to characterize five cis-acting higher-order RNA elements and one cis-acting process (translation) required for the replication of a coronavirus helper-dependent minireplicon (Dl RNA). These features are presumed requirements for the viral genome as well and are postulated to function in the formation of the RdRp replication complex. They also specifically address the enigma of how it is that coronavirus subgenomic mRNAs, synthesized on mRNA-length double-stranded intermediates and possessing termini identical to those on the genome (minimally 65 5' and 1633 3' nts), fail to replicate following transfection into helper virus-infected cells. The Dl RNA replicon is a 2.2 kb fusion product of the virus genomic termini and differs from mRNA 7 by only 421 nts of additional contiguous 5'-proximal sequence. It is postulated that sgmRNAs lack 3 of the necessary 5'-proximal signals for replication. The study has three specific aims: (1) To characterize the role of the phylogenetically-conserved 5'-proximal stem-loops Ill, IV, and V, including identification of the viral and cellular protein(s) that bind stem-loop III and the cellular protein(s) that binds stem-loop IV. (2) To characterize the cis-acting translation requirements for the (fused) partial la and entire N ORFs. (3) To characterize the 3' UTR cis-acting features of the phylogenetically conserved pseudoknot and its associated upstream bulged stem-loop, and the phylogenetically conserved octamer and its associated heptameric helix. Analyses will employ RNA structure probing, sitedirected mutagenesis, mass-spectrometric identification of binding proteins, and assays for DI RNA minus-strand synthesis, replication and packaging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR CALICIVIRUS

AND

ANTIGENIC

ANALYSIS

OF

HUMAN

Principal Investigator & Institution: Estes, Mary; Professor; Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-JAN-2000; Project End 31-DEC-2004 Summary: Norwalk virus, belonging to the family of Caliciviridae, is the major cause of epidemic non-bacterial gastroenteritis in humans. Norwalk virus represents an emerging virus based on an increased clinical significance of these agents being recognized as new methods to detect these viruses are utilized. Recent studies have found these viruses cause almost all (greater than 95 percent) outbreaks of nonbacterial gastroenteritis in the United States. This virus, which is exclusively a human pathogen, has a capsid structure formed by 180 copies of a single protein (ORF 2). A second protein (ORF 3) present in small amounts has recently been identified in virions. Studies of animal caliciviruses have identified persistent infections and some animal viruses have recently been shown to be genetically related to human caliciviruses. Multiple genetic types of caliciviruses exist and some of these represent different serotypes

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indicating it may be difficult to develop vaccines. Instead, other antiviral strategies need to be devised. Norwalk virus has not yet been cultivated in cell culture, but the cloning and expression of its genome resulted in the discovery that the capsid protein spontaneously assembles into virus-like particles (VLPs) when expressed using the baculovirus system. A high resolution 3.4 Angstrom units structure of the recombinant Norwalk virus VLPs, determined by X-ray crystallography, has shown that these particles exhibit T=3 icosahedral symmetry with a distinctive architecture that includes 90 arch-like capsomeres surrounding 32 large hollows. The atomic resolution structure together with biochemical analyses have provided insight into the nature of the chemical interactions that govern the assembly, disassembly, and receptor recognition, and allowed the formulation of testable hypotheses about mechanisms that may regulate these pathways. This grant application outlines experiments to continue to use structural, molecular, and biochemical approaches to understand the assembly, expression and antigenic properties of these unique singlestranded RNA human pathogens. The specific aims of the proposed studies are to continue (1) to dissect the molecular interactions that regulate capsid assembly and disassembly, (2) to understand the role of ORF 3 in genome encapsidation, and (3) to map antigenic and biologic domains on the virus capsid. Because of the unique features of the calicivirus structure, it is anticipated that the results obtained will provide the foundation needed to develop new types of antivirals. Expression systems of full-length and subgenomic RNAs also will be established in mammalian cell systems that may permit replication of infectious particles in cell culture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF BERBERINE-MEDIATED ANTITUMOR ACTIVITY Principal Investigator & Institution: Kang, Quan; Surgery; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): The objective of this fellowship application is to determine the gene expression profile in berberine-treated human cancer cells. An increasing amount of attention has been paid to the use of complementary and alternative medicine (CAM) as a part of the treatment for human cancer. A Chinese herb, Coptis chinensis, that is routinely used in China for treating gastroenteritis for thousands of years, may be developed as an anti-tumor agent. Coptis contains multiple constituents, and berberine is the major constituent. We have recently demonstrated that Coptis extract and berberine exhibit significant anti-proliferative activity in human cancer cells. However, the molecular mechanisms underlying Coptis or berberinemediated anti-tumor activity are unknown. In this application, I propose to conduct a comprehensive gene expression profiling analysis in berberine-treated human cancer cells by focusing on three specific aims. The first aim is to conduct hybridizations of RNA samples prepared from berberine-treated human cancer cells. The second aim is to conduct comprehensive bioinformatic analyses on the microarray data set. The third aim is to verify potentially important targets of berberine using Northern blotting or quantitative RT-PCR. Taken together, by analyzing the expression profile of nearly 40,000 genes, I expect to identify a set of target genes that may function as intracellular mediators of berberine's anti-cancer action. My long-term goal is to elucidate the molecular bases of berberine-mediated antitumor activity, and to investigate the possible use of berberine and its derivatives as effective chemotherapy and/or chemopreventive agents in human cancer.

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

Project Title: MOLECULAR DISSECTION OF THE CORONAVIRUS SPIKE Principal Investigator & Institution: Gallagher, Thomas M.; Associate Professor; Microbiology and Immunology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 15-DEC-1993; Project End 30-JUN-2008 Summary: (provided by applicant): The enveloped, RNA-containing murine coronaviruses include a large collection of strains. Each strain infects different tissues and thus causes a distinct disease such as hepatitis, gastroenteritis, or chronic encephalomyelitis; the latter serves as a model for human neurodegenerative diseases. This proposal will elucidate coronavirus entry mechanisms, and in doing so will explain how very similar strains cause such dramatically different diseases. A key determinant of coronavirus tropism is the spike (S), a protein that carries out essential virus entry functions. S proteins bind to carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors, which cause conformational changes culminating in virus-cell membrane fusion. The first aim will characterize the structural changes following interactions between S and CEACAM. We will specifically focus on novel biochemical features of the S proteins, such as their thiol-disulfide reactivities, as they relate to structural changes required for virus entry. We expect to provide new insights into protein-mediated membrane fusion reactions. The second aim will determine how cholesterol operates as a cofactor to support coronavirus entry. We will develop in vitro assays for virus fusion and use them to identify cholesterol-dependent stages of the Smediated fusion process. The third aim will connect our biochemical studies of coronavirus entry with in vivo investigations of disease. This will be accomplished by comparing viruses of variable neurovirulence in controlled in vitro measurements of SCEACAM binding and S-induced membrane fusion. Our results will relate the biochemical properties of the coronaviruses with their pathogenesis. Our collective findings will expand current knowledge of virus entry, and help set the stage for future antiviral drug developments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR MECHANISMS OF NORWALK VIRUS GENOME EXPRESSION Principal Investigator & Institution: Hardy, Michele E.; Veterinary Molecular Biology; Montana State University (Bozeman) Bozeman, Mt 59717 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 30-JUN-2004 Summary: The long-term research objective of this laboratory is to understand in detail, the molecular mechanisms of Norwalk virus genome expression and replication. Norwalk virus (NV) is the prototype strain of non-cultivable human caliciviruses that are the most important cause of epidemic outbreaks of acute gastroenteritis in humans. NV is considered an emerging virus, as new data based on more sensitive molecular assays indicate that infections with these viruses are more widespread than originally recognized. NV is an exclusively human pathogen, but other caliciviruses infect a broad range of animals and cause persistent, chronic and sometimes lethal infections in their hosts. The ability of the caliciviruses to persist and the potential for emergence, both in prevalence and pathogenesis, exemplify the importance of understanding the replication strategies of the virus at the molecular level. This application proposed studies to understand the viral protein functions critical for replication of the NV

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genome, and interactions with cellular proteins that regulate these functions. The specific aims of this proposal are 1) To understand the mechanisms of synthesis and processing of the NV non-structural proteins. The details of polyprotein synthesis and post- translation processing will be studied by expression of NV RNA in intestinal cellfree extracts. 2) To understand the mechanisms of control of NV genome expression in intestinal cells. NV non-structural protein synthesis and processing will be investigated in transfected intestinal cells expressing the ORF1 polyprotein. 3) To understand the functional interactions of NV non-structural proteins. Specific interactions of nonstructural proteins with RNA will be studied in intestinal cells expressing ORF1. NV and other caliciviruses are unique among animal viruses in structure and genome organization. Thus, detailed dissection of the functions of the NV non-structural proteins likely will lead to elucidation of new mechanisms of RNA virus genome expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MICROBIAL PATHOGENESIS TRAINING PROGRAM Principal Investigator & Institution: Villalta, Fernando; Professor; Microbiology; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: An emerging and reemerging infectious disease crisis exist throughout the world today. Further, bioterrorism using microbes or their products poses significant threat to the USA and the entire world. Because there is a national need for scientists with expertise and training in several areas of infectious diseases, in this fourth renewal application we are expanding the scope of our Molecular Parasitology Training Program into Molecular Microbial Pathogenesis Training Program to provide graduate training in pathogenesis of diseases caused by parasites, bacteria and viruses. There continues to be a need to increase the number of minority scientists who are conducting research in the area of tropical and infectious diseases. In order to address these issues we are requesting support to continue funding the Molecular Microbial Pathogenesis Training Program administered by the Department of Microbiology at Meharry Medical College. The proposed program will provide opportunity for training six African Americans or other graduate students who are committed to a career in infectious diseases. Twenty one core faculty members at Meharry Medical College and Vanderbilt University will participate in the proposed graduate training. The diseases to be investigated include, malaria, Leishmaniasis, African trypanosomiasis, American trypanosomiasis, AIDS, viral gastroenteritis and encephalitis, septic shock, endocarditis, periodontitis, and the emerging pathogens Mycobacterium tuberculosis Bartonella bacilliformis and Helicobacterpylori. Students in the program will meet the Ph.D. requirements of the graduate program at Meharry and the requirements of one of the three Ph.D. tracks in the Department of Microbiology: (i) microbiology and immunology; (ii) cell and molecular biology; and (iii) genetics. This training program will also include the yearly participation of the pre-doctoral students in a Tropical and Infectious Diseases Symposium which was initiated at Meharry in 1984 and continues to be the venue each Spring for outstanding research reports on recent advances in the biochemistry, molecular biology and immunology of Tropical and Infectious Diseases. Dr. Fernando Villalta, Professor in the Department of Microbiology at Meharry Medical College, will serve as a Program Director and will be responsible for the overall administration of the program. Dr. Maria F. Lima, Dean of the School of Graduate Studies at Meharry and member of this training program, will serve as a Co-Director together with Dr. Jacek Hawiger at Vanderbilt University. They will be assisted by the Molecular Microbial

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Pathogenesis Training Program Advisory Committee consisting of training faculty from Meharry and Vanderbilt as well as an External Advisory Committee. Each trainee's Committee on Instruction will include members of Meharry faculty and a faculty mentor from Vanderbilt. In addition, each trainee will take at least one didactic course at Vanderbilt and participate in training there as needed. All trainees and faculty in the program will participate in a seminar series that include presentations by faculty and students in the program. This is a strong research training program administered at an institution with an excellent record of recruiting and retaining minority students in graduate programs. The goals of the proposed training program will be enhanced by the increasing number of collaborative research and training programs at Meharry and Vanderbilt resulting from a formal alliance between the institutions in 1999. The support requested will provide unique opportunities for these students and provide a positive step to address the shortage of research on emerging infections as well as the shortage of minority scientists in this discipline. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEASE

MOLECULAR

STUDIES

OF HUMAN CYTOMEGALOVIRUS

Principal Investigator & Institution: Tong, Liang; Biological Sciences; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (Adapted from Applicant's Abstract) Human cytomegalovirus (HCMV), a herpesvirus, is a major opportunistic infectious agent in individuals suffering from AIDS, as well as individuals with suppressed immune systems (for example, organ and bone marrow transplant recipients). Both primary and reactivated latent HCMV infections can cause severe acute diseases in these individuals, such as retinitis, pneumonitis, hepatitis and gastroenteritis. Current therapies against HCMV infections are mostly targeted at the DNA polymerase of the virus, and are limited in their usefulness by their toxic side effects. In addition, viral resistance to anti-herpes agents is becoming an increasingly more significant problem. Therefore, new and efficacious treatments for HCMV infections, and herpesvirus infections in general, are highly desirable. The protease of herpesviruses is essential for their life cycle, and represents a novel target for the design and development of anti-herpes chemotherapeutic agents. Several classes of inhibitors against HCMV protease have been reported, but none of these have sufficient potency and/or pharmacokinetic properties. Breakthroughs are needed to develop a new generation of inhibitors against the protease, with higher potency, metabolic stability, and oral bioavailability. Structure-based drug design can play an important role in this process, as it has in the development of AIDS therapeutic agents targeted at the HIV protease. Such design efforts require a detailed structural and biochemical knowledge of the protein target, which are currently still lacking for HCMV protease. Despite being a serine protease, HCMV protease has many unique biochemical and structural features and belongs to a new class of serine protease, distinct from the classical serine proteases such as chymotrypsin and subtilisin. Therefore, a new body of knowledge is needed on this new class of enzymes. The proposed research will use structural, biochemical and biophysical techniques to achieve a greater understanding of the molecular basis for the inhibition and the catalytic mechanism of HCMV protease. Special emphasis will be placed on studying the unique features of the protease, such as the Ser-His-His catalytic triad, the requirement for dimerization for activity, the activation by antichaotropic agents, the conformational flexibility and the induced fit behavior, and the inhibition of the protease by non-peptidic and peptidomimetic

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compounds. The crystal structure of HCMV protease free enzyme and the recently determined structure of the protease inhibitor complex represent an excellent starting point for the performance and completion of the proposed research. A long-term goal of the research is to expand the studies to include the proteases of other herpesviruses, many of which (herpes simplex virus and Kaposi's sarcoma associated herpesvirus) are also targets for the development of anti-herpes agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEEDLE-FREE DELIVERY OF SUBUNIT ROTAVIRUS VACCINES Principal Investigator & Institution: Choi, Anthony H.; Emerging Concepts, Inc. 3130 Highland Ave, Ste 3115 Cincinnati, Oh 45219 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Rotavirus is the most common cause of severe gastroenteritis in infants causing nearly 1 million deaths worldwide and costing the United States 1.5 billion dollars annually. The only FDA-approved rotavirus vaccine was withdrawn in 1999 because of its association with bowel obstruction (intussusception). We are developing subunit rotavirus vaccines, one of which contains the powerful bacterial enterotoxin adjuvant LT(R192G). When delivered intranasally or orally in mice, this vaccine formulation induces nearly complete protection against rotavirus shedding after oral challenge. To increase the safety and ease of delivery of this candidate vaccine, we propose to compare three needle-free immunization methods at the skin using the mouse model: (1) Topical application (transcutaneous immunization) of the protein formulation, (2) Delivery of the protein formulation using a needleless injecting device, and (3) Delivery of a DNA form of the formulation using the injection device. Each delivery method will include LT(R192G). In Phase II SBIR studies, we will refine and prepare the most effective vaccine formulation for initial safety studies in humans. In Phase III SBIR studies, we will continue safety, immunogenicity and efficacy trials in humans and seek FDA approval. Successful development of VP6-based vaccines would be important for society and commercially significant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NSP4 STIMULATED ION CHANNELS AND AGE-DEPENDENT DIARRHEA Principal Investigator & Institution: Morris, Andrew P.; Integr Biol/Pharm/Physiology; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Rotaviruses are a major cause of life-threatening diarrhea in infants and children worldwide. Following viral infection, diarrhea is seen associated with pathophysiological changes in mucosal fluid and electrolyte balance. My group has focused on defining a new pathophysiological component to diarrhea. We have shown that a rotaviral non-structural protein called NSP4 induces diarrhea in both normal and cystic fibrosis mouse pups accompanied by calcium-sensitive chloride secretory current generation by gastrointestinal mucosa. Neither diarrhea nor anion secretion occur in adult mice. At the sub-cellular level, NSP4 causes phospholipase C sensitive intracellular calcium (Ca2+)i mobilization and calcium-sensitive halide influx into mucosal crypts. NSP4-induced (Ca2+)i mobilization (our assay for receptor occupancy) is not age-dependent. Thus, we hypothesize that NSP4 activates and agedependent calcium-sensitive chloride channel in pup mucosa causing chloride secretion,

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and secretory diarrhea. We propose studies in native cells to identify and characterize the electrophysiological and pharmacological properties of the chloride channel, and thus unequivocally demonstrate a role for this conductance in NSP4 mediated agedependent cellular halide influx. We intend to identify the cellular signaling mechanisms coupling NSP4 mediated changes in (Ca2+)i to this conductance. These mechanistic studies may identify novel targets for pharmacological intervention with clear clinical relevance. These goals will provide the cellular basis for the age-dependent secretory diarrhea and may identify a molecular target for rotaviral-induced transepithelial anion secretion. They will also translate facts established for the biophysics of calcium-activated chloride channel expression in cultured epithelial celllines into the fields of clinical medicine and disease. In doing so, our results will provide an excellent possibility for development of new therapies for rotaviral gastroenteritis, and for other infectious diseases in children where altered mucosal (Ca2+)i homeostasis occurs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOP REGULON AND SALMONELLA VIRULENCE Principal Investigator & Institution: Miller, Samuel I.; Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-FEB-1991; Project End 31-MAY-2006 Summary: (provided by the applicant): Salmonella are facultative intracellular pathogens which cause significant diseases in humans and animals. These organisms are responsible for several disease syndromes, including enteric (typhoid) fever, gastroenteritis, bacteremias and focal infections. Typhoid fever is a severe systemic illness which is mostly a problem in the developing world and in travelers. Nontyphoidal salmonella infections are increasing in the USA and are largely associated with contaminated food. Salmonellae infections are most severe in infants, the elderly, and in immunosuppressed individuals. This grant proposes to study the mechanism by which Salmonellae survive host innate immune killing. Innate immune killing involves the non-antigen specific mechanisms by which animals eliminate invading bacteria. Included in innate immune mechanisms are antimicrobial peptides produced at mucosal surfaces and within phagocytic cell granules and cytokines produced in response to recognition of bacterial lipid A. Pathogens such as Salmonellae have mechanisms to resist these killing mechanisms that are environmentally regulated. The genes encoding these mechanisms are the subject of this grant. They include the virulence regulators PhoP/PhoQ that respond to signals within host tissues and induce genes necessary for resistance to innate immune killing. These regulators are essential for human and animal virulence. PhoP/PhoQ regulate genes involved in surface remodeling of bacteria. These genes include those responsible for modification of the lipid and protein components of the outer membrane. This grant proposes to define the mechanism by which these modifications are generated and the role of surface remodeling in bacterial virulence. The specific aims of this proposal are to define the genes involved in lipid A modification and the effects of these modifications on bacterial virulence and host cell recognition of lipid A. In addition a variety of genomic and proteomic techniques will be used to fully define the genes regulated by PhoP/PhoQ to better understand the coordinately regulated response of bacteria to host colonization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF GASTROINTESTINAL EOSINOPHILS Principal Investigator & Institution: Rothenberg, Marc E.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Eosinophil accumulation in the gastrointestinal tract occurs in numerous diseases (i.e. food allergy, eosinophilic gastroenteritis, allergic colitis, and gastroesophageal reflex). Some of these disorders are highly prevalent and clinically important. For example, food allergy has been documented in 2-4% of children and can by life threatening. Despite the common finding of eosinophils in tissue specimens from these patients, and increasing evidence that these cells have a pathogenic role in these disorders, there has been only a limited understanding of the biological and pathological significance of eosinophils in the gastrointestinal tract. We have begun to elucidate the mechanisms of eosinophil trafficking into the gastrointestinal tract and have developed a novel model of food allergen-induced gastrointestinal inflammation. This grant application proposes to elucidate the cellular and molecular mechanisms involved in regulating eosinophil trafficking into the gastrointestinal tract. The application is based on the main hypothesis that eosinophils normally reside in the gastrointestinal tract and that their homing into this organ is regulated by locally generated eotaxin, a CC chemokine with eosinophil selective activity, that works cooperatively with interleukin (IL)-5. The regulation of gastrointestinal eosinophils by these two cytokines and T cells will be evaluated in healthy states, following oral allergen challenge in the model of allergen-induced gastrointestinal inflammation, and by transgenic over-expression of these cytokines specifically in the intestine. Four aims will be undertaken: (I) the mechanisms of eosinophil homing into the gastrointestinal tract during health states; (ii) characterization of the early and late phase response in the gastrointestinal tract during allergic inflammation; (iii) the mechanism of eosinophil trafficking into the gastrointestinal tract during allergic inflammation; and (IV) the consequences of transgenic expression of eotaxin and IL-5 in the intestine. The proposed experiments will define the mechanisms that regulate gastrointestinal eosinophils at baseline and following acute (allergic) and chronic (transgenic) inflammatory stimuli in the gastrointestinal tract. These basic studies will hopefully provide a better understanding of physiological processes in the gastrointestinal tract and diseases processes such as food allergy which may be related, at least in part, to dysregulation of eosinophil trafficking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXPRESSION

REGULATION

OF

HUMAN

CYTOMEGALOVIRUS

GENE

Principal Investigator & Institution: Stinski, Mark F.; Professor; Microbiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-1976; Project End 31-MAY-2006 Summary: (provided by applicant): Human cytomegalovirus (HCMV) can cause congenital neurological damage and disseminated infections resulting in pneumonitis, retinitis, hepatitis, and gastroenteritis. HCMV infections have been associated with accelerated atherosclerosis and with coronary restenosis following angioplasty. HCMV infections in solid organ and bone marrow transplant recipients are a significant cause of morbidity. Both hematopoietic cells of the bone marrow and monocytes of the blood can be latently infected with HCMV. Productive infection occurs in a variety of terminally differentiated cells including fibroblast, cytotrophoblast, smooth muscle,

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endothelial, epithelial, and mircoglial cells and in macrophages. Abortive infection occurs in polymorphonuclear cells. Our laboratory is interested in viral DNA regulatory elements and in viral and cellular proteins that regulate latency, persistent infection, and productive infection. In Specific Aim I, we propose to determine the role of specific regulatory elements in the proximal 3'-end of the major immediate early (MIE) enhancer on viral gene expression in undifferentiated cells relevant to HCMV latency. Regulatory elements that function to repress transcription from the MIE promoter upon binding a regulator protein in undifferentiated cells of the myeloid lineage will be mutated in the context of the viral genome, and recombinant viruses will be analyzed. In Specific Aim II, we propose to characterize a repressor-boundary region 5' to the MIE enhancer that prevents the MIE enhancer from affecting transcription from the flanking UL1 27 promoter. We have identified a repressor-boundary region between the UL127 promoter and the MIE enhancer that is unique to HCMV and to date, not found in other herpesviruses or DNA viruses. Due to its location, the repressor-boundary region has a role in the temporal expression of the immediate early (IE) and early HCMV genes that flank the MIE enhancer. Downstream of the MIE promoter are the MIE genes, IE1 and 1E2, which encode for proteins of 72 (1E72) and 86 kDa (lE86), respectively. These viral proteins are key regulatory proteins for efficient productive infection. In Specific Aim Ill, we propose to determine early gene regulation in recombinant viruses with both the IEl and IE2 genes deleted and to determine the effects of HCMV tEl and 1E2 gene products on viral and host cell gene expression relevant to the viral life cycle. We will investigate the functions of this replication defective HCMV in activation of viral or cellular gene expression and compare these functions to those of the 1E72 and 1E86 proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH TRAINING IN INFECTIONS AND IMMUNITY Principal Investigator & Institution: Tweardy, David J.; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This is a new NRSA application to support two postdoctoral trainees per year for five years This award will substantially increase the ability of talented trainees to exploit outstanding opportunities to pursue research training in infectious diseases at Baylor College of Medicine. At this time, no NRSA exists within Baylor College of Medicine or the Texas Medical Center to pursue clinical research training in non-AIDS infections. Yet, there is increasing need for trained professionals capable of performing clinically based research directed at treatment and prevention of non-AIDS infections that threaten the health of US citizens, including ageold scourges such as infectious gastroenteritis and pneumonia and new threats posed by bioterrorism. Superb training opportunities exist at Baylor College of Medicine in a number of areas, including biodefense. Participating projects with a strong record of federal funding and training experience include: 1) Innate Immunity and Nosocomial Infections; 2) Parasitic Infections; 3) Viral and Bacterial Gastroenteritis; 4) Viral Oncogenesis; 5) Acute Respiratory Pathogens; 6) Vaccine Evaluations; 7) Tuberculosis; 8) Helicobacter pylori Infection; and 9) Prostheses Infections. Total grant support in 2002 for the specific centers and programs participating in this NRSA Program is $19,769,825. The structure of the Program for Research Training in Infections and Immunity will contain three components that represent general training tracks that can be pursued by trainees: 1) laboratory-based clinical research; 2) clinical research trials; and 3) clinical epidemiology. All trainees will be encouraged to participate in the Clinical Scientist Training Program at Baylor College of Medicine and obtain their Masters Degree in

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Clinical Investigation. Those pursuing the clinical epidemiology track may opt for a MPH Degree at the University of Texas-Houston School of Public Health. The Adult Infectious Diseases Training Program at Baylor College of Medicine has shown it can attract highly qualified postdoctoral trainees, half of them women and close to a quarter underrepresented minorities, and point them in the direction of future infectious diseases clinical research. In the past two years, this program has produced graduates who have successfully pursued each of the three training pathways proposed. Altogether, these four individuals have published 26 original peer-reviewed manuscripts and have been awarded several prestigious grants and career development awards, totaling $1,862,500. This recent track record is offered as evidence in support of the request for two postdoctoral trainees per year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RIBOZYMES FOR STUDIES AND TREATMENT OF HCMV INFECTIONS Principal Investigator & Institution: Liu, Fenyong; Associate Professor; None; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: Human cytomegalovirus (HCMV), a member of the human herpesviruses, causes one of the most common opportunistic infections encountered in patients with AIDS. Disseminated HCMV infection in these patients is usually associated with gastroenteritis, pneumonia, and sight-threatening retinitis. However, genetic analyses of this virus to characterize gene products essential for viral replication and pathogenesis and to identify new targets for drug development have been hampered since it grows slowly and propagates only in human culture. Meanwhile, the emergence of drug- resistant HCMV strains to the available drugs has posed a need to develop new drugs and novel strategies to combat HCMV infections. This proposal represents our research program to develop ribonuclease P (RNase P) ribozyme as a gene targeting tool for studies of the functions of HCMV genes and as a therapeutic agent for the treatment of HCMV infections. Recently, we have shown that gene-targeting RNase P ribozyme (MIGS RNA) efficiently cleaves mRNA substrates in vitro, including the mRNAs coding for the HCMV major transcription regulator proteins, IE1 and lE2, and are effective in inhibiting the expression of these mRNAs and HCMV replication in cell culture. Further studies on the catalytic mechanism and sequence specificity of these ribozymes are necessary in order to improve their efficacy in inhibiting HCMV gene expression and replication. In this research program, highly efficient and sequence-specific MIGS RNAs will be generated to target the mRNAs encoding IE1/1E2 proteins and the protease (PR) which is essential for HCMV capsid maturation. Moreover, biochemical studies will be carried out to understand how these ribozymes achieve efficient cleavage activity and high sequence specificity. Finally, the efficacy and sequence-specificity of these ribozymes in inhibiting the expression of the viral mRNAs will be determined, and whether they are highly effective and specific in abolishing HCMV replication will be studied. This study will reveal whether MIGS ribozymes can be used as gene targeting tools to study the functions of HCMV essential genes and furthermore, will facilitate the development of these ribozymes as therapeutic agents for the inhibition of gene expression and replication of HCMV and other human viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Gastroenteritis

Project Title: ROLE OF HUMAN MILK IN INFANT NUTRITION AND HEALTH Principal Investigator & Institution: Morrow, Ardythe L.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 01-JUL-1979; Project End 31-MAR-2003 Summary: The competitive renewal of our program project grant application is submitted by investigators who propose to continue their studies on the unique properties of human milk. All projects address the biologic consequences through protocols which utilize in vitro assays, animal models, and humans. The projects generally seek to define and characterize factors in human milk that protect newborn infants from disease. Certain consequences of the luminal milk gastrointestinal tract interactions that pertain to protection of the infant will continue to be examined. Animal models will be utilized with study of human subjects is not possible, but human infants will be studied whenever appropriate. The respective projects and subcontracts will consider: 1) the role of soluble milk factors in the prevention of shigellosis; 2) the antiinflammatory characteristics of human milk; 3) the role of the secretory immune system in viral enteric pathogen infection; 4) isolation, characterization and testing of the protective factor(s) in human milk against heat-stable enterotoxin of E. coli; and 5) the role of human milk in the prevention of Campylobacter infection. Each of the projects will be supported by epidemiology/statistical, biochemical, and molecular biology core sections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF SUBSTANCE P IN INTESTINAL INFLAMMATION Principal Investigator & Institution: Pothoulakis, Charalabos; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 15-SEP-1994; Project End 30-NOV-2008 Summary: (provided by applicant): Several pieces of evidence indicate that substance P (SP) via binding to high affinity neurokinin-1 receptor (NK-1R) plays a critical role in the modulation of inflammatory responses in many organs, including the GI tract. Thus, both SP and NK-1R receptor expression is increased in the small intestine and colon of animal models of intestinal inflammation and in the colonic mucosa of patients with inflammatory bowel disease (IBD), and Clostridium difficile associated colitis. We showed that NK-1R are localized in colonic epithelial cells and lamina propria macrophages and that binding of SP to these receptors activates the nuclear factor kappaB (NF-kappaB) leading to the release of proinflammatory cytokines. NK-1R communicates with the epidermal growth factor receptor (EGFR) and such communication plays an important role in the development of prolonged colitis. Moreover, IL-1beta, and TNF-alpha, two cytokines linked to colonic inflammation, can upregulate the NK-1R by a mechanism involving the NF-kappaB/IkappaB system. However, the signaling pathways involved in SP-induced NF-kappaB activation and increased expression of proinflammatory genes is not known. As well, very little is known on the molecular events leading to increased NK-1R expression during colonic. The central hypothesis in this proposal is that the NF-kappaB/lkappaB system is critical in both, SP-induced upregulation of proinflammatory genes, as well as in upregulation of its receptor. An additional hypothesis is that SP-mediated NK-1R-EGFR trans activation is linked to proinflammatory signaling pathways, important for the development of acute colitis. Aim 1 will elucidate the participation of the NFkappaB/IkappaB system in substance P-neurokinin- 1 receptor-induced proinflammatory signaling in colonic epithelial cells by determining the specific kinases

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and Ird3 isoforms targeted following SP receptor binding. Aim 2 will examine the role of MAP kinases and MAP kinase-related pathways in SP-NK-1R - induced NFrd3 activation in proinflammatory gene expression in colonic epithelial cells. Involvement of Ras and EGFR activation will also be determined. Aim 3 will define the molecular mechanisms regulating neurokinin-1 receptor gene expression in THP-1 cells and examine the importance of these mechanisms in lamina propria macrophages. Our results will provide important insights on the mechanisms of SP-NK-1R mediated proinflammatory signaling in inflammatory responses, including human colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROTAVIRUS VP4: STRUCTURE AND FUNCTION Principal Investigator & Institution: Dormitzer, Philip R.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Each year, rotavirus gastroenteritis kills an estimated 600,000 children, worldwide, and hospitalizes approximately 60,000 children, in the U.S. Since the withdrawal of a rotavirus vaccine, it is again a major childhood illness for which no immunization is available. The process of cell entry by rotavirus is a major target for intervention against disease. To initiate infection, rotavirus translocates a large, transcriptionally active particle across a membrane and into the cytoplasm. The outer layer of the non-enveloped rotavirus particle is the delivery apparatus that accomplishes this poorly understood translocation. The outer capsid contains two proteins, VP7 and VP4, both of which participate actively in entry and are targets of neutralizing antibodies. VP7 causes uncoating on loss of calcium. VP4, a spike protein, is cleaved by trypsin to prime the virus for infection. VP4 is central to the mechanism of membrane penetration. It contains a head domain and a membrane interaction domain. We have purified uncleaved VP4, primed the purified protein with protease, determined the structure of the head domain, and crystallized the primed form of the membrane interaction domain. Using these crystals, we will solve the structure of the primed conformation of the membrane interaction domain. This structure will be used to refine strategies for the structural analysis of the uncleaved conformation of VP4. We will also determine the structures of functionally important VP4 variants. We have developed a "recoating genetics" system for rotavirus by recoating subviral particles with purified, recombinant VP4 and VP7, boosting infectivity by 4 to 5 orders of magnitude. This system will allow analysis of the effect of engineered mutations, including structure-based mutations, on the function of VP4 during cell entry. Mutational studies will clarify the determinants of sialic acid-dependence, protease priming, and membrane penetration. Cell culture-based assays using recoated particles will focus on separating carbohydrate, lipid, and protein binding during entry using structure-based mutations and on blocking entry-associated conformational changes by introducing reversible disulfide cross-links. These structural and functional studies will clarify the rotavirus entry pathway, provide a model for entry by non-enveloped viruses, and define the structural basis for rotavirus neutralization by antibodies against VP4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SALMONELLA ANTIMICROBIAL PEPTIDE RESISTANCE Principal Investigator & Institution: Gunn, John S.; Associate Professor; Molecular Virology, Immunology & Medical Genetics; Ohio State University 1960 Kenny Road Columbus, Oh 43210

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Timing: Fiscal Year 2004; Project Start 15-JUL-1998; Project End 31-DEC-2008 Summary: (provided by applicant): Salmonellae are facultative intracellular pathogens that cause disease in humans and animals, including enteric (typhoid) fever and gastroenteritis. Typhoidal and non-typhoidal salmonellosis continues to cause significant morbidity and mortality worldwide. The overall objectives of this work are to better understand the induction of pathogenic bacterial gene expression in response to eukaryotic cell environments, as well as how bacteria utilize regulatory networks induced within these environments to avoid host innate immune killing. Antimicrobial peptides (AP), found at mucosal surfaces and within phagocytes, are a key weapon in the host innate immune arsenal. Two-component regulatory systems enable bacteria to sense their external environment and to mount an adaptive response by altering gene expression. Two such systems in Salmonella that are induced within the host during infection (PhoP-PhoQ; PmrA-PmrB) interact to remodel the outer membrane, including the lipopolysaccharide (LPS), which is the primary surface molecule that interacts with AP. We have recently identified a third member of this two-component cascade, UblAUblB. PmrA-PmrB mediated modifications render the LPS less anionic, which leads to a reduced sensitivity to cationic AP, and these modifications have been shown to be necessary for oral virulence in mice. Further study of the in vivo induced PmrA-PmrB system and its role in LPS modification and virulence is necessary to better understand Salmonella pathogenesis and resistance to host innate immune killing. The aims of this grant are: (1) Characterization of novel PmrA-PmrB-regulated genes, (2) The role of PmrA-PmrB-mediated LPS modification in Salmonella virulence, and (3) The interaction of the UblA-UblB and PmrA-PmrB two-component regulatory systems. Understanding these regulated mechanisms by which salmonellae survive within the animal host could lead to novel therapeutic, preventative and diagnostic strategies, and are likely to be applicable to the studies of other bacterial pathogens of humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL TRANSDUCTION IN ENTEROCOCCI Principal Investigator & Institution: Perego, Marta; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2004; Project Start 15-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Enterococci are Gram-positive constituents of the human microflora and play beneficial roles in artisanal cheese production and as probiotics to treat gastroenteritis. Enterococci have emerged as one of the leading causes of nosocomial infections. The problem of enterococcal infection has been aggravated by the emergence of multiple antibiotic resistance that poses a serious challenge to therapeutic intervention. This is an issue of concern in medicine, to the scientific community and the general public. Direction in the search for new therapeutic approaches for treating enterococcal infections will come from a clearer understanding of the factors involved in the pathogenesis of the disease and their regulatory mechanisms. The availability of the E. faecalis genome sequence allowed us to identify the key components of the bacterial regulatory mechanisms carried out by twocomponent signal transduction systems. The research proposed in this application has the goal of defining the regulatory network of enterococcal signal transduction for the purpose of understanding the mechanisms underlying the physiology of these organisms. This will provide valuable information for the understanding of mechanisms responsible for pathogenicity and antibiotic resistance and thus the identification of molecular targets for therapeutic intervention. We have generated deletion mutants for all response regulators identified in E. faecalis V583. Phenotypes have been identified in

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some strains, and a role for the FsrA response regulator in controlling biofilm formation through regulation of gelatinase production has been revealed. We propose to: 1) determine the role of two-component systems in virulence through in vivo analyses; 2) determine the role of gelatinase in biofilm; 3) define the genes regulated by twocomponent signal transduction systems (the regulon) by transcriptional and proteomic approaches; 4) determine the role of the two-component systems in enterococcal physiology by turning ON or OFF the genes encoding response regulatory proteins and analyzing the resulting phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOLAR WATER DISINFECTION: RANDOMIZED INTERVENTION TRIAL Principal Investigator & Institution: Colford, John M.; Public Hlth Bio & Epidemiology; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): More than one third of the population in rural and in peri-urban areas of developing countries have no access to sufficient or clean drinking water free of pathogens. Thus, waterborne gastroenteritis remains a major infrastructural and public health problem particularly, as effective treatment (filtration, chlorination, treatments plants) is often beyond financial means or environmental resources used for water purification (fire-boiling, burning carbon-based fuels) become scarce in those communities. In this context solar disinfection of drinking water is especially appealing using a combination of irradiation by direct sunlight and solar heating to kill the water-borne pathogens in contaminated drinking water. To date, the efficacy of the SODIS technology as a home-based, low-cost intervention to provide safe drinking water in low income countries is well established, and a large-scale promotion and dissemination program is under way in seven Latin American countries. The principal objective of this study is to evaluate the effectiveness of home-based solar water disinfection (SODIS) in reducing the burden of gastrointestinal illness in children under 5 years in rural villages participating in a country-wide Bolivian SODIS program. We will conduct a community (cluster)-randomized controlled trial following a cohort of children under age 5 in each community. Totally, 22 communities will be selected from among those districts designated by the country-program to receive the SODIS intervention. A pair-matched design will be employed where communities are first ranked according to their baseline incidence of diarrheal disease and the intervention then assigned within each of the 11 consecutive pairs of communities randomly to one of them. In each cluster, 30 children (660 in total) will be enrolled and followed up for 12 months. Data on diarrheal illness will be obtained from morbidity diaries kept by mothers and validated through weekly home visits. Stool samples will be collected during the baseline morbidity surveys and at times of a diarrheal episode in a child during follow-up. Water quality monitoring of raw water sources used for drinking water and of water samples after treatment with the SODIS device will be conducted systematically. Mothers of participating children will be interviewed at baseline and during the trial with regard to current water use, behavioral and environmental exposures of their child in the home and within the community. This study will specifically estimate: (1) how much of the efficacy of the SODIS technology established in laboratory experiments and in two tightly controlled phase-Ill trials can be retained as effectiveness, i.e., under program conditions; (2) the preventive fraction of all-cause child-diarrhea attributable to SODIS; and (3) pathogen-specific attributable risks of diarrheal illness and the cost-effectiveness of SODIS will be calculated. The project is

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organized by the University of California, Berkeley, with its substantial experience in water intervention trials in U.S. and it benefits from the tradition of North-South collaboration in public health research of the Swiss Tropical Institute, Basel, Switzerland. It is run jointly with the Bolivian partners at the Universidad Mayor de San Simon and the Fondazion SODIS that coordinates the Bolivian SODIS program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES ON ROTAVIRUSES Principal Investigator & Institution: Prasad, Bidadi V.; Professor; Biochem and Molecular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-DEC-1988; Project End 31-JAN-2003 Summary: Rotavirus is the major cause of several, life-threatening gastroenteritis in young children and animals. Rotaviruses are large (1000 A), complex, icosahedral assemblies. This virus has been the subject of extensive biochemical, genetic and structural studies because of its medical relevance, intriguing structural complexity, and unique strategies of morphogenesis and replication. Rotaviruses contain 11 segments of double- stranded RNA encapsulated within three concentric capsid layers. Of the 11 proteins encoded by the genome, six are structural (VP1, VP2, VP3, VP4, VP6 and VP7) and five are non-structural (NSP1-5). In the last three years, they have made exciting new discoveries that have provided a better characterization of the rotavirus, structure and a deeper insight into the structural basis of various virus functions such as trypsinenhanced infectivity, virus assembly and endogenous transcription. These recent developments, together with other developments in the molecular biology of rotaviruses and related systems, have allowed plans for more in-depth dissection of structurefunction correlations in rotavirus using high resolution electron cryomicroscopy together with computer image reconstruction techniques and X-ray crystallographic information. The specific objectives of the proposed project are: 1) To further investigate the structural basis of protease-enhanced infectivity in rotavirus, and localize the various functional domains in the VP4 spike structure using monoclonal antibodies and recombinant virus-like particles. 2) To further understanding of the structural basis of endogenous transcription in rotavirus. 3) To carry out higher resolution structural characterization of rotavirus to understand protein-protein interactions that modulate various functions of the virus. 4) To carry out structural analysis of NSP4, an intracellular receptor, and study its interaction with VP6, and viral cell attachment protein VP4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDY OF INTRAVENOUS ONDANSETRON FOR CONTROL OF GASTROENTERITIS Principal Investigator & Institution: Moe, Christine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURVEILLANCE OF HUMAN CALICIVIRUS IN CHINA Principal Investigator & Institution: Jiang, Xi; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229

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Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Acute infectious gastroenteritis is one of the most important diseases in China. Based on a nationwide surveillance of 21 provinces in 1988, there were 863 million diarrheal episodes per year in China, of which 290 million occurred in children under 5 years of age. Limited studies on human calicivirus (HuCV)-associated gastroenteritis have been performed in developing countries, including China. The hypotheses of this study are that HuCVs play an important role in acute gastroenteritis in children and adults in China and that new HuCV strains with genetic and antigenic properties distinct from currently known strains exist. These hypotheses will be fulfilled by the following specific aims: 1. To determine the role of HuCVs as a cause of severe diarrhea in children and of outbreaks of acute gastroenteritis in the general population by a nationwide surveillance in ten cities and one rural area in China. 2. To determine genetic variation of epidemic strains of HuCVs by cloning and sequencing strains detected in stool specimens from the surveys as well as from historic collections of stool specimens from children. 3. To extend understanding of the genetic variation of HuCVs by cloning the entire capsid gene of newly discovered strains and to develop EIAs by expression of the viral capsid protein in baculovirus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUSCEPTIBILITY NOROVIRUSES

AND

PROTECTIVE

IMMUNITY

TO

Principal Investigator & Institution: Baric, Ralph S.; Associate Professor; Epidemiology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Norwalk-like viruses (NLV), a genus within the Caliciviridae, are the major cause of epidemic gastroenteritis in the US and a significant cause of severe diarrhea in young children. Based on their low infectious dose, high transmissibility and economic impact, NLVs have been classified as Bioterrorism Category B Priority Pathogens by the U.S. Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. The long-term goals of this proposal are to elucidate the molecular mechanisms governing human susceptibility to NLV infection. In this capacity, we will use human challenge models to test various hypotheses that specific human susceptibility alleles and acquired immune factors determine NLV infection outcomes and pathogenicity. It is anticipated that the identification of host factors and responses that influence NLV pathogenesis will reveal fundamental insights into the molecular biology of these viruses, simultaneously allowing for the development of NLV vaccine and therapeutic strategies. A second goal is to develop NLV vaccines using alphaviruses as heterologous vaccine vectors. Venezuelan equine encephalitis virus (VEE)-based vaccines elicit high levels of mucosal and systemic immunity against NLVs. We will test various hypotheses that VEE replicon particles (VRPs) encoding different genogroup I and II (GI and GII) NLV capsid genes elicit strong systemic, cellular and mucosal immune responses against homologous and heterologous NLVs and are superior to the current standards for NLV vaccine development (NLV recombinant virus-like particles (VLPs) and edible vaccines). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRAL GASTROENTERITIS PATHOGENS Principal Investigator & Institution: Matson, David O.; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002 Summary: Rotaviruses and caliciviruses account for 10 to 50% of gastroenteritis episodes in children worldwide. This project will define further the relevant antibodies and glycoconjugates that protect infants from RV diarrhea with the overall goal of preventing infection and illness despite antigenic diversity. Recent breakthroughs in the molecular characterization of CVs have permitted development of new assays and genetic comparisons that have superseded previous diagnostic methods and classifications of CVs. The new assays have not been applied to longitudinal studies of closely monitored children and assessment of infection, correlates of protection, and non-immunoglobulin protective factors in such studies are likely to yield new information of seminal importance to our understanding of CVs. Our hypothesis is that antibody and non-antibody factors bind viral gastroenteritis pathogens and protect breast-fed infants from disease. The hypothesis will be addressed by the following specific aims: 1. To measure antibody levels in the cohort and associate those antibodies with protection against rotavirus and calicivirus infection and illness. 2. To examine non-antibody factors in human milk that are associated with protect against rotavirus and calicivirus infection and illness in the suckling. 3. To determine whether maternal immunization with rotavirus vaccine results in enhanced protection against rotavirus diarrhea in breast-fed infants. 4. To determine whether antibody to rotavirus nonstructural protein 4 (NSP4), a potential viral enterotoxin, is a correlate of protection against rotavirus infection, and illness and whether human milk contains antibody or non-antibody factors that bind to NSP4. 5. To assess the immunomodulating effect of human milk on response to rotavirus vaccination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRAL GASTROENTERITIS--BASIS OF PROTECTION AND VIRULENCE Principal Investigator & Institution: Greenberg, Harry B.; Senior Associate Dean for Research; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-1984; Project End 31-MAR-2004 Summary: Group A Rotaviruses are highly important human pathogens. Estimates of their impact on man include worldwide mortality rates of 800,000 to 1 million infant deaths annually. Despite substantial progress over the past two decades in determining rotavirus gene structure and function, we still do not have a clear understanding of the basis of rotavirus immunity, virulence or host tropism. It is the purpose of this proposal to continue our investigation of several aspects of rotavirus pathogenesis, including host range restriction, virulence and immunity. The specific aims of this application are: 1) To identify the viral and immunologic determinants of protective immunity in vivo. We will carry out a series of experiments in a mouse model to correlate the quantity and specificity of the local and systemic humoral immune response with protection. In order to determine why homologous infection induces local IgA responses more efficiently than heterologous infection, we will characterize the T helper cell response in the gut and spleen after murine and non-murine rotavirus infection of suckling mice. We further propose to identify and characterize the viral targets of protective immunity. Protection studies will be carried out in the adult mouse challenge model with homologous, heterologous and ressortant viruses that vary serologically. Immunization

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studies will also be carried out using specific recombinant viral gene products or killed virion delivered to various mucosal or systemic sites. We plan to determine which specific arm of the immune system mediates protective immunity. Passive transfer studies will be carried out employing isolated populations of immune effectors cells (CD4+, and/or CD8+T cells and/or B cells derived from various tissues) from immune MHC-matched donors. We will also study the cellular determinants of protective immunity using mice deficient in specific components of the immune system. 2) To identify the viral and immunologic determinants for the resolution of rotavirus infection. We will determine if CD4+ as well as CD8+ T cells or local IgA antibody are capable of mediating resolution of infection by themselves when passively transferred into chronically infected SCID mice. Mice deficient in specific immune functions will be also be examined to determine if they ar fully or partially deficient in their ability to resolve infection and/or if immune cells taken from such animals can eliminate rotavirus infection in chronically infected SCID mice. 3) To determine the target of and mechanism by which IgA and other monoclonal antirotavirus antibodies prevent, and possibly resolve, rotarvirus infection in vitro and in vivo. In order to study the role of IgA directly we will carry out challenge studies in mice bearing transplanted rotavirusspecific IgA secreting hybridomas. Finally, we will investigate the mechanism by which IgA and IgG neutralizing monoclonals directed at VP7 or VP4 inhibit viral replication. 4) To determine the genetic and molecular basis of host range restriction and virulence. It is our hypothesis that the surface proteins of rotavirus are important but not exclusive determinants of virulence; that virulence and host range determinants vary depending on the genetic and physiological context of the analysis and that genes encoding nonstructural as well as structural proteins may be important determinants of host range restriction. In order to determine the genetic basic of host range restrictions and virulence, we will carry out genotypic and phenotypic analyses of rotavirus reassortants in the infant mouse model. In order to better understand the molecular and virologic basis of virulence and/or host tropism, we will identify relevant steps in the viral replication cycle in vivo that are restricted on the basis of host range. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRULENCE NETWORKS IN SALMONELLA Principal Investigator & Institution: Miller, Virginia L.; Professor; Molecular Microbiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 28-FEB-2006 Summary: (Applicant's Abstract): Salmonella is one of the most extensively characterized bacterial pathogens and is a leading cause of bacterial gastroenteritis. With the aging of the population we are likely to see further increases in the incidence of this infection, and we can expect an increase in the severity of disease because the elderly are more susceptible to disease and tend to have more severe infections. It is clear that the SPI1 encoded type III secretion apparatus and the proteins secreted by this apparatus play a major role for invasion of the epithelium, recruitment of PMNs, and diarrhea. A better understanding of this system and its role in pathogenesis of diseases caused by Salmonella should lead to better methods of treatment and prevention. We recently identified the sigDE locus of S. typhimurium; sigD encodes an effector protein secreted by the SPI1 type III secretion apparatus (note: effector proteins are those believed to have a direct effect on host cells). Like other effectors in this system, expression of sigDE requires SirA and HilA, but as with other effectors, expression of sigDE is probably not directly affected by these regulators. The current model suggests that SirA turns on expression of HilA which turns on expression of invF. InvF is thought

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to activate expression of genes encoding the effectors; we have demonstrated that InvF is required for sigD expression. In addition, a screen for regulators of sigD identified SicA (encoded by SPI1). SicA is thought to be a chaperone for SipB and SipC. How expression of the type III secretion system and expression of the translocators and effector proteins is coordinated remains an important question. These are the questions we hope to address in this proposal with the long-term goal of understanding how these events are integrated with other virulence factors of Salmonella to cause disease. Specifically we propose the following: Aim 1. Which transcriptional units are regulated by InvF and SicA? To test this we will identify the key transcriptional units and will examine expression of reporter constructs in different mutant backgrounds. Aim 2. How do SicA and InvF mediate regulation of the sigDE and other promoters? To do this we will examine the interactions of SicA and InvF with each other and the promoters they regulate. Aim 3. To identify other effectors secreted by the SPI1 type III secretion pathway by identifying InvF regulated genes. These will be characterized for their role in virulence related assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WATERBORNE EMERGING DIARRHEAL DISEASES STUDY (WEDDS) Principal Investigator & Institution: Griffiths, Jeffrey K.; Associate Professor; Family Medicine & Cmty Health; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: (provided by applicant): Al 43415, the 'Waterborne Emerging Diarrheal Diseases Study' or WEDDS study, is designed to link environmental emerging waterborne disease pathogens, especially Cryptosporidium parvum, with disease in human hosts. The central hypothesis of this study is that drinking water that meets current public health standards is nonetheless a source of exposure to this class of emerging pathogens. The WEDDS specific aims remain:I. Construct, and clinically follow over time, a cohort of mfants and children and their families, closely monitoring their clinical and immunological status concerning Cryptosporidium via fecal sampling, serological testing, and assays of ceilular immunity.2. Quantify childhood population-wide infection rates with Cryptosporidium via repeated large, prospective, anonymous pediatric point-prevalence serological surveys.3. Evaluate the temporal and seasonal associations between indicators of Cryptosporidium contamination in three major drinking water supplies, and the various measures of human exposure, infection, and disease described in Specific Aims 1 and 2, and in HMO gastroenteritis datasets.4. Validate this approach by (4a) linking patient and environmental oocysts using molecular methods, and (4b) monitoring the presence of Giardia and microsporidia in water supplies.The specific aim of this supplemental proposal is to quantify the patterns and extent of gastroenteritis and cryptosporidiosis in Massachusetts elderly, using sophisticated mathematical tools, standardized serological testing, and geographical information systems mapping, and compare this information with that obtained from our other sentinel population, children, which are being studied in the parent WEDDS grant. In this study we will:1. Quantify the incidence of GI infectious a) among elderly in Massachusetts in 1990-2000 using HCFA records, and records of laboratoryconfirmed cases of cryptosporidiosis via the Massachusetts passive surveillance system; and b) among elderly in the Boston metropolitan area in 1998-2001 using records of gastrointestinal infections and seroprevalence of antibodies in samples obtained via an intervention trial based in Massachusetts nursing homes;2. Examine the link between

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the gastrointestinal illness and drinking water supply using Geographical Information Systems and spatial statistical analysis. 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 “gastroenteritis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for gastroenteritis in the PubMed Central database: •

Ability of TESTPACK ROTAVIRUS enzyme immunoassay to diagnose rotavirus gastroenteritis. by Chernesky M, Castriciano S, Mahony J, Spiewak M, Schaefer L.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266919

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Application of a Reverse Transcription-PCR for Identification and Differentiation of Aichi Virus, a New Member of the Picornavirus Family Associated with Gastroenteritis in Humans. by Yamashita T, Sugiyama M, Tsuzuki H, Sakae K, Suzuki Y, Miyazaki Y.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87158

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Application of PCR to detect Norwalk virus in fecal specimens from outbreaks of gastroenteritis. by Moe CL, Gentsch J, Ando T, Grohmann G, Monroe SS, Jiang X, Wang J, Estes MK, Seto Y, Humphrey C, et al.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263100

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Astrovirus as a cause of gastroenteritis in Japan. by Utagawa ET, Nishizawa S, Sekine S, Hayashi Y, Ishihara Y, Oishi I, Iwasaki A, Yamashita I, Miyamura K, Yamazaki S.; 1994 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263888

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Characterization and seroepidemiology of a type 5 astrovirus associated with an outbreak of gastroenteritis in Marin County, California. by Midthun K, Greenberg HB, Kurtz JB, Gary GW, Lin FY, Kapikian AZ.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263593

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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Characterization of a variant strain of Norwalk virus from a food-borne outbreak of gastroenteritis on a cruise ship in Hawaii. by Herwaldt BL, Lew JF, Moe CL, Lewis DC, Humphrey CD, Monroe SS, Pon EW, Glass RI.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263153

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Characterization of an unclassified microaerophilic bacterium associated with gastroenteritis. by Archer JR, Romero S, Ritchie AE, Hamacher ME, Steiner BM, Bryner JH, Schell RF.; 1988 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266203

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Clinical and epidemiological features of acute infantile gastroenteritis associated with human rotavirus subgroups 1 and 2. by Uhnoo I, Svensson L.; 1986 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268692

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Clinical features of acute infantile gastroenteritis associated with human rotavirus subgroups I and II. by Steele AD, Bos P, Alexander JJ.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266963

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Comparison of three enzyme immunoassays to tissue culture for the diagnosis of rotavirus gastroenteritis in infants and young children. by Christy C, Vosefski D, Madore HP.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267945

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Cytopathic astrovirus isolated from porcine acute gastroenteritis in an established cell line derived from porcine embryonic kidney. by Shimizu M, Shirai J, Narita M, Yamane T.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269575

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Detection and analysis of a small round-structured virus strain in oysters implicated in an outbreak of acute gastroenteritis. by Le Guyader F, Neill FH, Estes MK, Monroe SS, Ando T, Atmar RL.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168251

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Detection of antibody to recombinant Norwalk virus antigen in specimens from outbreaks of gastroenteritis. by Monroe SS, Stine SE, Jiang X, Estes MK, Glass RI.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266146

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Diagnosis of Noncultivatable Gastroenteritis Viruses, the Human Caliciviruses. by Atmar RL, Estes MK.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88960

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Elevated levels of immunoglobulin A to Giardia lamblia during a waterborne outbreak of gastroenteritis. by Birkhead G, Janoff EN, Vogt RL, Smith PD.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267657

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Epidemiologic Typing of Salmonella enterica Serotype Enteritidis in a Canada-Wide Outbreak of Gastroenteritis due to Contaminated Cheese. by Ahmed R, Soule G,

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Demczuk WH, Clark C, Khakhria R, Ratnam S, Marshall S, Ng LK, Woodward DL, Johnson WM, Rodgers FG.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86822 •

Epidemiological Patterns of Rotaviruses Causing Severe Gastroenteritis in Young Children throughout Australia from 1993 to 1996. by Bishop RF, Masendycz PJ, Bugg HC, Carlin JB, Barnes GL.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87877

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Epidemiology of Astrovirus Infection in Young Children Hospitalized with Acute Gastroenteritis in Melbourne, Australia, over a Period of Four Consecutive Years, 1995 to 1998. by Mustafa H, Palombo EA, Bishop RF.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86338

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Evaluation of Salmonella typhimurium Mutants in a Model of Experimental Gastroenteritis. by Everest P, Ketley J, Hardy S, Douce G, Khan S, Shea J, Holden D, Maskell D, Dougan G.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96587

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Food-Borne Outbreak of Gastroenteritis Associated with Genogroup I Calicivirus. by Johansson PJ, Torven M, Hammarlund AC, Bjorne U, Hedlund KO, Svensson L.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120226

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Gastroenteritis outbreaks associated with Norwalk-like viruses and their investigation by nested RT-PCR. by O'Neill HJ, McCaughey C, Wyatt DE, Mitchell F, Coyle PV.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37403

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Gastroenteritis, sepsis, and osteomyelitis caused by Plesiomonas shigelloides in an immunocompetent host: case report and review of the literature. by Ingram CW, Morrison AJ Jr, Levitz RE.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269334

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Homotypic and heterotypic antibodies for prevention of experimental rotavirus gastroenteritis. by Losonsky GA, Vonderfecht SL, Eiden J, Wee SB, Yolken RH.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269095

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Identification and Type Distribution of Astroviruses among Children with Gastroenteritis in Colombia and Venezuela. by Medina SM, Gutierrez MF, Liprandi F, Ludert JE.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87413

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Identification of minireovirus as a Norwalk-like virus in pediatric patients with gastroenteritis. by Lew JF, Petric M, Kapikian AZ, Jiang X, Estes MK, Green KY.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=236832

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Importance of rotavirus and adenovirus types 40 and 41 in acute gastroenteritis in Korean children. by Kim KH, Yang JM, Joo SI, Cho YG, Glass RI, Cho YJ.; 1990 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268162

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Increased Prevalence of G1P[4] Genotype among Children with Rotavirus-Associated Gastroenteritis in Metropolitan Detroit. by Abdel-Haq NM, Thomas RA, Asmar BI, Zacharova V, Lyman WD.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156486

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Klebsiella pneumoniae gastroenteritis masked by Clostridium perfringens. by Rennie RP, Anderson CM, Wensley BG, Albritton WL, Mahony DE.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269578

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Laboratory identification of adenoviruses associated with gastroenteritis in Canada from 1983 to 1986. by Brown M.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267982

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Large-Scale Survey of Campylobacter Species in Human Gastroenteritis by PCR and PCR --Enzyme-Linked Immunosorbent Assay. by Lawson AJ, Logan JM, O'neill GL, Desai M, Stanley J.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85830

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Longitudinal Studies of Neutralizing Antibody Responses to Rotavirus in Stools and Sera of Children following Severe Rotavirus Gastroenteritis. by Coulson BS.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96221

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Major Change in the Predominant Type of "Norwalk-Like Viruses" in Outbreaks of Acute Nonbacterial Gastroenteritis in Osaka City, Japan, between April 1996 and March 1999. by Iritani N, Seto Y, Haruki K, Kimura M, Ayata M, Ogura H.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86988

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Molecular Characterization of Isolates of Waterborne Cryptosporidium spp. Collected during an Outbreak of Gastroenteritis in South Burgundy, France. by Dalle F, Roz P, Dautin G, Di-Palma M, Kohli E, Sire-Bidault C, Fleischmann MG, Gallay A, Carbonel S, Bon F, Tillier C, Beaudeau P, Bonnin A.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156555

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Molecular Detection of Human Calicivirus among Spanish Children with Acute Gastroenteritis. by Roman E, Negredo A, Dalton RM, Wilhelmi I, Sanchez-Fauquier A.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130898

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Molecular Detection of Human Calicivirus in Young Children Hospitalized with Acute Gastroenteritis in Melbourne, Australia, during 1999. by Kirkwood CD, Bishop RF.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88222

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Molecular epidemiologic evidence for association of thermostable direct hemolysin (TDH) and TDH-related hemolysin of Vibrio parahaemolyticus with gastroenteritis. by Shirai H, Ito H, Hirayama T, Nakamoto Y, Nakabayashi N, Kumagai K, Takeda Y, Nishibuchi M.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313699

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Molecular Epidemiology of an Outbreak of Febrile Gastroenteritis Caused by Listeria monocytogenes in Cold-Smoked Rainbow Trout. by Miettinen MK, Siitonen A, Heiskanen P, Haajanen H, Bjorkroth KJ, Korkeala HJ.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85164

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Molecular Epidemiology of Caliciviruses Causing Outbreaks and Sporadic Cases of Acute Gastroenteritis in Spain. by Buesa J, Collado B, Lopez-Andujar P, Abu-Mallouh R, Rodriguez Diaz J, Garcia Diaz A, Prat J, Guix S, Llovet T, Prats G, Bosch A.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120653

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Molecular Epidemiology of Outbreaks of Gastroenteritis Associated with Small Round-Structured Viruses in East Anglia, United Kingdom, During the 1996 --1997 Season. by Maguire AJ, Green J, Brown DW, Desselberger U, Gray JJ.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84173

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New Zealand White Rabbit as a Nonsurgical Experimental Model for Salmonella enterica Gastroenteritis. by Hanes DE, Robl MG, Schneider CM, Burr DH.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98790

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Norwalk virus-associated gastroenteritis traced to ice consumption aboard a cruise ship in Hawaii: comparison and application of molecular method-based assays. by Khan AS, Moe CL, Glass RI, Monroe SS, Estes MK, Chapman LE, Jiang X, Humphrey C, Pon E, Iskander JK, et al.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263031

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Outbreak of human calicivirus gastroenteritis in a day-care center in Sydney, Australia. by Grohmann G, Glass RI, Gold J, James M, Edwards P, Borg T, Stine SE, Goldsmith C, Monroe SS.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269815

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Patients with enteric adenovirus gastroenteritis admitted to an Australian pediatric teaching hospital from 1981 to 1992. by Grimwood K, Carzino R, Barnes GL, Bishop RF.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227894

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Plesiomonas shigelloides bacteremia in a healthy girl with mild gastroenteritis. by Paul R, Siitonen A, Karkkainen P.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267951

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Prevalence of Norwalk-Like Virus Infections in Cases of Viral Gastroenteritis among Children in Osaka City, Japan. by Iritani N, Seto Y, Kubo H, Murakami T, Haruki K, Ayata M, Ogura H.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153863

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Quantitative studies of invasion of rabbit ileal mucosa by Salmonella typhimurium strains which differ in virulence in a model of gastroenteritis. by Amin II, Douce GR, Osborne MP, Stephen J.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186143

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Real-Time PCR Detection of Salmonella in Suspect Foods from a Gastroenteritis Outbreak in Kerr County, Texas. by Daum LT, Barnes WJ, McAvin JC, Neidert MS, Cooper LA, Huff WB, Gaul L, Riggins WS, Morris S, Salmen A, Lohman KL.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120641

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Rotavirus-associated gastroenteritis in black infants in South Africa. by Steele AD, Alexander JJ, Hay IT.; 1986 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268773

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Rotavirus-specific cytotoxic T lymphocytes passively protect against gastroenteritis in suckling mice. by Offit PA, Dudzik KI.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=248814

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Sensitive Detection of RNA Viruses Associated with Gastroenteritis by a HangingDrop Single-Tube Nested Reverse Transcription-PCR Method. by Ratcliff RM, Doherty JC, Higgins GD.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139724

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Studies with enteroaggregative Escherichia coli in the gnotobiotic piglet gastroenteritis model. by Tzipori S, Montanaro J, Robins-Browne RM, Vial P, Gibson R, Levine MM.; 1992 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258311

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Survey of rotavirus G and P types associated with human gastroenteritis in Sao Paulo, Brazil, from 1986 to 1992. by Shif I.; 1995 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=228379

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Use of solid-phase immune electron microscopy for classification of Norwalk-like viruses into six antigenic groups from 10 outbreaks of gastroenteritis in the United States. by Lewis D, Ando T, Humphrey CD, Monroe SS, Glass RI.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227978

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Vibrio-associated gastroenteritis in the lower Cross-River Basin of Nigeria. by Ndon JA, Udo SM, Wehrenberg WB.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270509

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Western blot (immunoblot) assay of small, round-structured virus associated with an acute gastroenteritis outbreak in Tokyo. by Hayashi Y, Ando T, Utagawa E, Sekine S, Okada S, Yabuuchi K, Miki T, Ohashi M.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267662

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

A case of gastroenteritis associated with gastric trichuriasis. Author(s): Hong ST, Lim HS, Kim DH, Kim SJ. Source: Journal of Korean Medical Science. 2003 June; 18(3): 429-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808334

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A guidelines-based approach for managing acute gastroenteritis in children. Author(s): Gallagher C. Source: Journal for Specialists in Pediatric Nursing : Jspn. 2003 July-September; 8(3): 10710. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942889

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A large infantile gastroenteritis outbreak in Albania caused by multiple emerging rotavirus genotypes. Author(s): Villena C, Gabrieli R, Pinto RM, Guix S, Donia D, Buonomo E, Palombi L, Cenko F, Bino S, Bosch A, Divizia M. Source: Epidemiology and Infection. 2003 December; 131(3): 1105-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14959777

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An outbreak of food-borne gastroenteritis caused by Clostridium perfringens carrying the cpe gene on a plasmid. Author(s): Tanaka D, Isobe J, Hosorogi S, Kimata K, Shimizu M, Katori K, Gyobu Y, Nagai Y, Yamagishi T, Karasawa T, Nakamura S. Source: Japanese Journal of Infectious Diseases. 2003 June; 56(3): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944687

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An outbreak of Norwalk-like virus gastroenteritis in an aged-care residential hostel. Author(s): Liu B, Maywood P, Gupta L, Campbell B. Source: New South Wales Public Health Bulletin. 2003 June; 14(6): 105-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907999

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'Benign convulsions with mild gastroenteritis'--a worldwide clinical entity. Author(s): Posner E. Source: Brain & Development. 2003 October; 25(7): 529. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571917

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Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis. Author(s): Hakansson S, Kallen K. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 June; 33(6): 757-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801309

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Childhood gastroenteritis due to Aeromonas hydrophila in Ibadan, Nigeria. Author(s): Kehinde AO, Bakare RA, Oni AA, Okesola AO. Source: Afr J Med Med Sci. 2001 December; 30(4): 345-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510117

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Clinical pathway using rapid rehydration for children with gastroenteritis. Author(s): Phin SJ, McCaskill ME, Browne GJ, Lam LT. Source: Journal of Paediatrics and Child Health. 2003 July; 39(5): 343-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887663

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Comparison of phenotypic and genotypic characteristics of Salmonella bredeney associated with a poultry-related outbreak of gastroenteritis in Northern Ireland. Author(s): Moore JE, Murray L, Fanning S, Cormican M, Daly M, Delappe N, Morgan B, Murphy PG. Source: The Journal of Infection. 2003 July; 47(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850160

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Diagnostic accuracy of stool assays for inflammatory bacterial gastroenteritis in developed and resource-poor countries. Author(s): Gill CJ, Lau J, Gorbach SL, Hamer DH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 365-75. Epub 2003 July 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884161

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Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study. Author(s): Parry SD, Stansfield R, Jelley D, Gregory W, Phillips E, Barton JR, Welfare MR. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1970-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499773

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Eosinophilic gastroenteritis with ascites: a case report and review of the literature. Author(s): Fenoglio LM, Benedetti V, Rossi C, Anania A, Wulhfard K, Trapani M, Scalabrino E, Alberto G, Novero D, Cavalloperin P. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 1013-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772805

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Eosinophilic gastroenteritis: review of the literature. Author(s): Losanoff JE, Sauter ER. Source: Digestive Diseases and Sciences. 2003 November; 48(11): 2214; Author Reply 2215. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705831

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Explosive outbreaks of gastroenteritis in the shipboard environment attributed to Norovirus. Author(s): Bohnker BK, Thornton S. Source: Military Medicine. 2003 May; 168(5): Iv. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775163

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Factors affecting length of hospitalization of infants and children for recurrent gastroenteritis in Western Australia. Author(s): Lee AH, Wang K, Gracey M, Yau KK. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 July; 92(7): 843-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892166

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Factors influencing hospitalisation of infants for recurrent gastroenteritis in Western Australia. Author(s): Wang K, Yau KK, Lee AH. Source: Methods of Information in Medicine. 2003; 42(3): 251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874657

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FactSheet: Viral gastroenteritis. Author(s): NSW Department of Health. Source: New South Wales Public Health Bulletin. 2003 September-October; 14(9-10): 2067. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578954

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Fatal case of Salmonella enterica subsp. arizonae gastroenteritis in an infant with microcephaly. Author(s): Mahajan RK, Khan SA, Chandel DS, Kumar N, Hans C, Chaudhry R. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5830-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662995

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Gastroenteritis and antibiotic-associated diarrhea. Author(s): Jabbar A, Wright RA. Source: Primary Care. 2003 March; 30(1): 63-80, Vi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825250

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Gastroenteritis outbreak with norovirus in a Swiss university hospital with a newly identified virus strain. Author(s): Khanna N, Goldenberger D, Graber P, Battegay M, Widmer AF. Source: The Journal of Hospital Infection. 2003 October; 55(2): 131-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529638

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High hepatocyte growth factor levels in faeces during acute infectious gastroenteritis. Author(s): Nayeri F, Almer S, Brudin L, Nilsson I, Akerlind B, Forsberg P. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(11-12): 858-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723362

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Hypoglycemia complicating dehydration due to acute gastroenteritis. Author(s): Reid S, McQuillan S, Losek J. Source: Clinical Pediatrics. 2003 September; 42(7): 641-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552524

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Incidence of gastroenteritis in Norway--a population-based survey. Author(s): Kuusi M, Aavitsland P, Gondrosen B, Kapperud G. Source: Epidemiology and Infection. 2003 August; 131(1): 591-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948356

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Lethal gastroenteritis associated with clozapine and loperamide. Author(s): Eronen M, Putkonen H, Hallikainen T, Vartiainen H. Source: The American Journal of Psychiatry. 2003 December; 160(12): 2242-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638602

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Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. Author(s): King CK, Glass R, Bresee JS, Duggan C; Centers for Disease Control and Prevention. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 November 21; 52(Rr-16): 1-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627948

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Molecular characterization of isolates of waterborne Cryptosporidium spp. collected during an outbreak of gastroenteritis in South Burgundy, France. Author(s): Dalle F, Roz P, Dautin G, Di-Palma M, Kohli E, Sire-Bidault C, Fleischmann MG, Gallay A, Carbonel S, Bon F, Tillier C, Beaudeau P, Bonnin A. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2690-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791906

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Nosocomial outbreak of norovirus gastroenteritis and investigation of ABO histoblood group type in infected staff and patients. Author(s): Meyer E, Ebner W, Scholz R, Dettenkofer M, Daschner FD. Source: The Journal of Hospital Infection. 2004 January; 56(1): 64-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706273

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Outbreak of severe rotavirus gastroenteritis among children--Jamaica, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 November 14; 52(45): 1103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614409

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Persistent gastroenteritis in children infected with astrovirus: association with serotype-3 strains. Author(s): Caballero S, Guix S, El-Senousy WM, Calico I, Pinto RM, Bosch A. Source: Journal of Medical Virology. 2003 October; 71(2): 245-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938199

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Physician variation in test ordering in the management of gastroenteritis in children. Author(s): Powell EC, Hampers LC. Source: Archives of Pediatrics & Adolescent Medicine. 2003 October; 157(10): 978-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557158

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Prevalence and characterization of astroviruses in Argentinean children with acute gastroenteritis. Author(s): Espul C, Martinez N, Noel JS, Cuello H, Abrile C, Grucci S, Glass R, Berke T, Matson DO. Source: Journal of Medical Virology. 2004 January; 72(1): 75-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635014

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Prevalence of gastroenteritis among 4-year-old children in South Australia. Author(s): Heyworth JS, Baghurst P, McCaul KA. Source: Epidemiology and Infection. 2003 June; 130(3): 443-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825728

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Pseudohypoaldosteronism presenting as acute gastroenteritis: report of one case. Author(s): Yu MC, Hou JW. Source: Acta Paediatr Taiwan. 2003 January-February; 44(1): 44-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800385

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Rotaviral and bacterial gastroenteritis in children during winter: an evaluation of physician ordering patterns. Author(s): Chemaly RF, Yen-Lieberman B, Schindler SA, Goldfarb J, Hall GS, Procop GW. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 September; 28(1): 44-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927750

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Rotavirus detection and characterisation in outbreaks of gastroenteritis in aged-care facilities. Author(s): Marshall J, Botes J, Gorrie G, Boardman C, Gregory J, Griffith J, Hogg G, Dimitriadis A, Catton M, Bishop R. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 December; 28(3): 331-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522072

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Rotavirus gastroenteritis among children under five years of age in Izmir, Turkey. Author(s): Kurugol Z, Geylani S, Karaca Y, Umay F, Erensoy S, Vardar F, Bak M, Yaprak I, Ozkinay F, Ozkinay C. Source: Turk J Pediatr. 2003 October-December; 45(4): 290-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768791

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Rotavirus gastroenteritis associated with afebrile convulsion in children: clinical analysis of 40 cases. Author(s): Hung JJ, Wen HY, Yen MH, Chen HW, Yan DC, Lin KL, Lin SJ, Lin TY, Hsu CY. Source: Chang Gung Med J. 2003 September; 26(9): 654-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651163

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Sequence heterogeneity among human picobirnaviruses detected in a gastroenteritis outbreak. Author(s): Banyai K, Jakab F, Reuter G, Bene J, Uj M, Melegh B, Szucs G. Source: Archives of Virology. 2003 December; 148(12): 2281-91. Epub 2003 September 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648286

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Serotypic and antibiotic susceptibility pattern of Salmonella species isolated from cases of gastroenteritis at Infectious Diseases Hospital (IDH), Delhi from 1997-2000. Author(s): Das S, Gupta S, Mukesh. Source: J Commun Dis. 2002 December; 34(4): 237-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710854

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Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion. Author(s): Kawashima H, Inage Y, Ogihara M, Kashiwagi Y, Takekuma K, Hoshika A, Mori T, Watanabe Y. Source: Life Sciences. 2004 January 30; 74(11): 1397-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706570

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Utility of multilocus sequence typing as an epidemiological tool for investigation of outbreaks of gastroenteritis caused by Campylobacter jejuni. Author(s): Sails AD, Swaminathan B, Fields PI. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4733-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532212

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Viral agents of acute gastroenteritis in German children: prevalence and molecular diversity. Author(s): Oh DY, Gaedicke G, Schreier E. Source: Journal of Medical Virology. 2003 September; 71(1): 82-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858413

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Viral gastroenteritis--a danger to the patient, a danger to the staff. Author(s): Appelboam R, Hammond E. Source: Anaesthesia. 2004 March; 59(3): 293-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984530

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Waterborne outbreak of gastroenteritis associated with a norovirus. Author(s): Parshionikar SU, Willian-True S, Fout GS, Robbins DE, Seys SA, Cassady JD, Harris R. Source: Applied and Environmental Microbiology. 2003 September; 69(9): 5263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957912

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Yersinia enterocolitica gastroenteritis among infants exposed to chitterlings--Chicago, Illinois, 2002. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 October 10; 52(40): 956-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534510

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

Finding Nutrition Studies on Gastroenteritis 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 “gastroenteritis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

Acute gastroenteritis in children. Source: Choudhuri, P K J-Indian-Med-Assoc. 1987 July; 85(7): 214-5 0019-5847

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Antiviral activity of interferon against transmissible gastroenteritis virus in cell culture and ligated intestinal segments in neonatal pigs. Author(s): Department of Veterinary Microbiology and Immunology, Ontario Veterinary, College University of Guelph, Canada. Source: Jordan, L T Derbyshire, J B Vet-Microbiol. 1994 January; 38(3): 263-76 0378-1135

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Comparative study of early-season prophylaxis using ivermectin with lungworm vaccination in the control of parasitic bronchitis and gastroenteritis in cattle. Author(s): Department of Veterinary Pathology, Royal Veterinary College, University of London, Hatfield, Herts., Gt. Britain. Source: Jacobs, D E Foster, J Gowling, G Pilkington, J G Fox, M T Ryan, W G VetParasitol. 1989 November; 34(1-2): 45-56 0304-4017

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Control of parasitic bronchitis and gastroenteritis in grazing cattle by strategic prophylaxis with ivermectin. Source: Armour, J Bairden, K Pirie, H M Ryan, W G Vet-Rec. 1987 July 4; 121(1): 5-8 0042-4900

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Diagnosis and symptomatic therapy of acute gastroenteritis. Source: Jergens, A.E. Compend-contin-educ-pract-vet. Trenton, N.J. : Veterinary Learning Systems Company. December 1994. volume 16 (12) page 1555-1564. 0193-1903

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Diagnosis of enteric pathogens in children with gastroenteritis. Author(s): Department of Microbiology (SEALS), The Prince of Wales Hospital, Randwick, NSW, Australia. Source: McIver, C J Hansman, G White, P Doultree, J C Catton, M Rawlinson, W D Pathology. 2001 August; 33(3): 353-8 0031-3025

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Early season parasitic gastroenteritis in calves and its prevention with ivermectin. Source: Jacobs, D E Fox, M T Ryan, W G Vet-Rec. 1987 January 10; 120(2): 29-31 00424900

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Enteric pathogens, intestinal permeability and nitric oxide production in acute gastroenteritis. Author(s): Northern Territory Clinical School, Flinders University, c/o Royal Darwin Hospital, Australia. Source: Kukuruzovic, R Robins Browne, R M Anstey, N M Brewster, D R Pediatr-InfectDis-J. 2002 August; 21(8): 730-9 0891-3668

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Eosinophilic esophagitis: A subset of eosinophilic gastroenteritis. Author(s): University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, 324 South 34th Street, Philadelphia, PA 19104, USA. Source: Liacouras, C A Markowitz, J E Curr-Gastroenterol-Repage 1999 June; 1(3): 253-8 1522-8037

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Eosinophilic gastroenteritis associated with food allergy and bronchial asthma. Author(s): Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Korea. Source: Park, H S Kim, H S Jang, H J J-Korean-Med-Sci. 1995 June; 10(3): 216-9 1011-8934

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Epitope mapping and the detection of transmissible gastroenteritis viral proteins in cell culture using biotinylated monoclonal antibodies in a fixed-cell ELISA. Author(s): Ohio Agricultural Research and Development Center, Ohio State University, Wooster. Source: Simkins, R A Saif, L J Weilnau, P A Arch-Virol. 1989; 107(3-4): 179-90 0304-8608

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Evaluation of doramectin in a programme for season-long control of parasitic gastroenteritis in calves. Author(s): Department of Pathology and Infectious Diseases, Royal Veterinary College (University of London), Hatfield, Hertfordshire. Source: Fisher, M A Jacobs, D E Hutchinson, M J Simon, A J Vet-Rec. 1995 September 16; 137(12): 281-4 0042-4900

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Extremely low sodium hypotonic rehydration solution for young children with acute gastroenteritis. Author(s): Department of Pediatrics, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, Taiwan, R.O.C. Source: Lin, S L Kong, M S Chang-Gung-Med-J. 2001 May; 24(5): 294-9

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Fatal hyponatraemic brain oedema due to common gastroenteritis with accidental water intoxication. Author(s): Department of Medicine, Soder Hospital, Stockholm, Sweden. Source: Sjoblom, E Hojer, J Ludwigs, U Pirskanen, R Intensive-Care-Med. 1997 March; 23(3): 348-50 0342-4642

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Implementing an evidence-based acute gastroenteritis guideline at a children's hospital. Author(s): Division of Health Policy and Clinical Effectiveness, Department of Neonatology, Children's Hospital Medical Center (CHMC), Cincinnati, Ohio, USA. Source: Perlstein, Paul H Lichtenstein, Philip Cohen, Mitchell B Ruddy, Richard Schoettker, Pamela J Atherton, Harry D Kotagal, Uma Jt-Comm-J-Qual-Improvolume 2002 January; 28(1): 20-30 1070-3241

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Interspecies aminopeptidase-N chimeras reveal species-specific receptor recognition by canine coronavirus, feline infectious peritonitis virus, and transmissible gastroenteritis virus. Source: Benbacer, L. Kut, E. Besnardeau, L. Laude, H. Delmas, B. J-virol. Washington, D.C. : American Society for Microbiology. January 1997. volume 71 (1) page 734-737. 0022-538X

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Milk formulas in acute gastroenteritis and malnutrition: a randomized trial. Author(s): Northern Territory Clinical School, Flinders University and Paediatric Department, Royal Darwin Hospital, Australia. Source: Kukuruzovic, R H Brewster, D R J-Paediatr-Child-Health. 2002 December; 38(6): 571-7 1034-4810

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Normal boron excretion levels and borates related gastroenteritis cases in Singapore. Author(s): Institute of Science and Forensic Medicine, Singapore. Source: Chao, T C Ho, M L Cheng, H K Lo, D S Chen Bloodworth, B Singapore-Med-J. 1990 December; 31(6): 548-52 0037-5675

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Observation of curative effect on eosinophilic gastroenteritis by treatment with method of reinforcement of essence of the kidney. Author(s): Affiliated Hospital, Anhui College of Traditional Chinese Medicine, Hefei. Source: Bo, Y J-Tradit-Chin-Med. 1996 September; 16(3): 186-9 0254-6272

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Outbreak of Salmonella enteritidis phage type 913 gastroenteritis associated with mung bean sprouts--Edmonton, 2001. Author(s): Capital Health-Regional Public Health, Edmonton, Alberta. Source: Honish, L Nguyen, Q Can-Commun-Dis-Repage 2001 September 15; 27(18): 1516 1188-4169

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Persistent diarrhoea following gastroenteritis. Author(s): Department of Paediatrics and Child Health, Faculty of Medicine, University of Natal, Durban, South Africa. Source: Haffejee, I E J-Diarrhoeal-Dis-Res. 1990 December; 8(4): 143-6 0253-8768

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Pre-admission management of acute gastroenteritis in children: too much or too little? Author(s): Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur. Source: Lee, W S Lee, S P Boey, C C Med-J-Malaysia. 1999 March; 54(1): 22-5 0300-5283

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Prevention of parasitic gastroenteritis and parasitic bronchitis in first and second season grazing cattle. Author(s): Department of Veterinary Parasitology, Faculty of Veterinary Medicine, Ghent, Belgium. Source: Hollanders, W Berghen, P Dorny, P Hilderson, H Vercruysse, J Ryan, W G VetRec. 1992 April 18; 130(16): 355-6 0042-4900

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Prophylaxis of rotavirus gastroenteritis using immunoglobulin. Author(s): Division of Immunology, Research Institute Miyagi Cancer Center, Japan. Source: Ebina, T Arch-Virol-Suppl. 1996; 12217-23 0939-1983

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Treatment of rotaviral gastroenteritis with Qiwei Baizhu powder. Author(s): Institute of Combined Traditional Chinese and Western Medicine, Xiangya Hospital, Hunan Medical University, Changsha 410008, Hunan Province, China. [email protected] Source: He, S T He, F Z Wu, C R Li, S X Liu, W X Yang, Y F Jiang, S S He, G World-JGastroenterol. 2001 October; 7(5): 735-40 1007-9327

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Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source. Author(s): Robert Koch Institut, Wernigerode, Germany. Source: Tschape, H Prager, R Streckel, W Fruth, A Tietze, E Bohme, G Epidemiol-Infect. 1995 June; 114(3): 441-50 0950-2688

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. DISSERTATIONS ON GASTROENTERITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to gastroenteritis. 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 “gastroenteritis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on gastroenteritis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Gastroenteritis 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 gastroenteritis. 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: •

A Study of the Mechanisms Responsible for Diarrhea in an Acute Viral Enteritis in Piglets, Transmissible Gastroenteritis by Butler, Daniel George; PhD from University of Toronto (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK26042

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Antibody-dependent Cell-Mediated Cytotoxicity and Spontaneous Cell-Mediated Cytotoxicity in Porcine Transmissible Gastroenteritis by Cepica, Arnost; PhD from University of Guelph (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK55525

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The Use of Temporal-Spatial Analyses in the Epidemiological Investigation of Endemic and Epidemic Waterborne Gastroenteritis by Aramini, Jeffery Joseph; PhD from University of Guelph (Canada), 2003, 200 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75973

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Transmissible Gastroenteritis Virus : Growth in Organ Culture and Agar Gel Precipitation Reactions by Bohac, Jiri; PhD from University of Guelph (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK16318

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

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

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

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

Antibodies specific for the group antigen of astroviruses Inventor(s): Blacklow; Neil R. (Weston, MA), Herrmann; John E. (Northboro, MA) Assignee(s): University of Massachusetts Medical Center (worcester, Ma) Patent Number: 5,556,746 Date filed: June 14, 1994 Abstract: The present invention is based upon the discovery of a group antigen common to various types of astroviruses and the production of polyclonal and monoclonal antibodies reactive with this group antigen. The present invention encompasses the polyclonal antibodies, monoclonal antibodies, hybridoma cell lines which produce these monoclonal antibodies, and methods of using the monoclonal antibodies for diagnosing and treating gastroenteritis. Excerpt(s): Astroviruses were first visualized by electron microscopy (EM) of specimens from infants with gastroenteritis (Madeley et al., Lancet 2:451-452 (1975). Since that time, there have been several reports of infantile gastroenteritis due to astroviruses (Kurtz et al., J. Clin. Pathol. 30:94814 952 (1977); Madeley et al., J. Hyg. (Lond) 78:261-273 (1977); Ashley et al., J. Clin. Pathol. 31:939-943 (1978); Konno et al., J. Med. Virol. 9:11-17 (1982)). Infections in adults have also been reported and there have been suggestions that these viruses have been involved in food and water-borne outbreaks of gastroenteritis (Kurtz et al., Ciba Found. Symp. 128:92-107 (1987). In most studies, EM of stool samples has been the sole means of establishing the diagnosis of astrovirus infection. Kurtz and co-workers (Kurtz et al., J. Gen. Virol. 57:421-421 (1981) reported serial cultivation of the virus and later determined that five astrovirus types could be distinguished by serological methods (Kurtz et al., Lancet 2:1405 (1984). The true incidence of astrovirus infection has been difficult to establish because of the lack of convenient and efficacious identification and detection techniques. Diagnostic techniques using EM for observing the presence or absence of an astrovirus in a biological sample are labor-intensive and are not always reliable due to the risk of human error. According to Kurtz and co-workers, (Kurtz et al., Lancet 2:1405 (1984) astrovirus antisera is type specific. Therefore, an antiserum against one strain of astrovirus may not be capable of detecting a different strain of astrovirus. Web site: http://www.delphion.com/details?pn=US05556746__

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Diploid porcine embryonic cell strains, cultures produced therefrom, and use of said cultures for production of vaccines Inventor(s): Bordt; Dale Emil (Des Moines, IA), Thomas; Phillip Clay (Des Moines, IA) Assignee(s): Syntex (u.s.a.) Inc. (palo Alto, Ca) Patent Number: 4,070,453 Date filed: June 25, 1976 Abstract: Diploid porcine embryonic cell strains, method of growing same from porcine embryonic tissue, culturing and subculturing said diploid cell strains, and preparing a virus vaccine (exemplary of the virus vaccine thus prepared is a porcine transmissible gastroenteritis virus vaccine) from said diploid cell strain cultures. A novel nutrient

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growth medium composition for culturing and subculturing by serial subcultivation is also disclosed. Excerpt(s): This invention relates to cell strains, particularly to novel diploid porcine embryonic cell strains, methods of growing same from porcine embryonic tissue, culturing and subculturing said diploid cell strains, and preparing a virus vaccine, and particularly a porcine virus vaccine from said diploid porcine embryonic cell strain cultures. Exemplary of a vaccine thus prepared is one from porcine transmissible gastroenteritis virus. This invention also relates to a novel nutrient growth medium composition for culturing and subculturing said diploid porcine embryonic cell strains. It has been known to grow viruses which cause disease states in many species, such as porcine transmissible gastroenteritis (TGE) virus, bovine virus diarrhea (BVD) virus, infectious canine hepatitis (ICH) virus, rabies (R) virus, and hog cholera (HC) virus, and the like, in primary tissue cultures of porcine origin. However, the use of porcine primary tissue cultures for the growing of viruses suffers from the disadvantage that the porcine primary tissue cultures are prone to contamination with not easily detectable viruses and the probability of which cannot be thoroughly established prior to the actual use of the porcine primary tissue culture in vaccine component preparation. Hence, purity of vaccines prepared using porcine primary tissue cultures is not established until well after the preparation of the vaccine component. It had been proposed, as a theoretical alternative to the use of porcine primary tissue cultures for vaccine preparation, that cultures, termed continuous porcine cell lines, having the potential of being stored frozen and possessing unlimited growth potential be used. Such continuous cell lines can be established directly from tumors, arise unpredictably spontaneously from cell strains, or result from transformation of cell strains by certain viral or chemical means. Continuous cell lines are usually aneuploid with a subtetraploid karyotype and contain chromosomes displaying structural anomalies. Continuous cell lines do not display contact inhibition, but grow in dense piles of randomly arranged cells that have a "transformed" appearance from that of the normal cell. Web site: http://www.delphion.com/details?pn=US04070453__ •

Epithelial adhesive lactobacilli Inventor(s): Adlerberth; Ingegerd (Goteborg, SE), Ahrne; Siv (Bjarred, SE), Jeppsson; Bengt (Lund, SE), Johansson; Marie-Louise (Lund, SE), Molin; Goran (Lund, SE), Wold; Agnes (Goteborg, SE) Assignee(s): Probi AB (lund, Se) Patent Number: 6,159,465 Date filed: September 23, 1997 Abstract: The invention refers to the use of Lactobacillus plantarum 299v having a mannose-specific adhesin for the preparation of a pharmaceutical composition inhibiting the binding of pathogenic bacteria expressing mannose-specific adhesins to the epithelial cell surface. The strain of Lactobacillus plantiarum which can be used in the invention adheres to D-mannose-coated agarose beads. The invention also refers to the use of said strain for the preparation of a pharmaceutical composition to be used in prophylatic and/or curative treatment of bacterial translocation, gastroenteritis and other diseases caused by pathogenic bacteria expressing mannose-specific adhesins.

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Excerpt(s): The present invention refers to Lactobacillus strains which have the ability to adhere to epithelial cell surfaces, especially in the human intestinal mucosa, and which can be used for the prophylactic and/or curative treatment of bacterial disturbances caused by pathogenic bacteria adhering to the epithelial cell in a similar way. The indigenous microbiota is one of the major defense mechanisms that protect the human or animal body against colonization by invading bacteria. Immunosuppressed, antibiotic treated and parenterally fed patients are at a risk of infectious diseases like sepsis, meningitis or urinary tract infections produced by spread of bacteria mainly deriving form the normal fecal population. One mechanism behind this process can be bacterial translocation, which is defined as the passage of viable bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs. Blood poisoning, sepsis, is still a very common surgical complication in connection with abdominal surgery with a high death-rate. Bacteria or bacterial products may penetrate the malfunctioning intestinal wall and infect or induce malfunction in other remote organs, such as lungs, liver, heart etc. and this leads to multiple organ dysfunction or the so called intensive-care-disease. These patients are today treated by administration of antibiotics and surgical treatment of the abscess to the extent it could be located. At present antibiotics are conventionally administered before intestinal surgery in order to reduce the risk of postoperative infections and illness caused thereby. However, the treatment with antibiotics is associated with destruction of the normal intestinal flora and overgrowth with still more pathogenic bacteria. Web site: http://www.delphion.com/details?pn=US06159465__ •

Intestinal function using leptin Inventor(s): O'Connor; Darlise (Newark, DE), Schwartz; Marshall (Bryn Mawr, PA) Assignee(s): The Nemours Foundation (wilmington, De) Patent Number: 6,630,444 Date filed: October 23, 2000 Abstract: A method for treating a patient that has inadequate intestinal function is described. Administering leptin to a subject increases the intestinal function beyond that for a normal intestine and beyond that of a normal adaptive response. Further, administering leptin to a subject results in an increase in amino acid absorption, sugar absorption, mucosal mass, transport mechanisms for amino acids, or transport mechanisms for sugars. The method may be used for treating subjects have conditions such as short bowel syndrome, inflammation of the bowel, necrotizing enterocolitis, intestinal atresia, midgut volvulus, severe acute gastroenteritis, chronic gastroenteritis, cholera, chronic infections of the bowel, immunologic disorders affecting the small intestine, and inflammatory bowel disease such as, chronic ulcerative colitis and Crohn's Disease. Excerpt(s): The present invention relates broadly to enhancing the functions of the small intestine and the treatment of inflammatory bowel diseases in a patient by the administration of leptin. Short bowel syndrome ("SBS") is a devastating clinical disorder resulting from massive small bowel resection. SBS affects many infants and children and threatens normal growth and development. The remnant intestine naturally adapts to resection, however, this adaptation process is often inadequate to meet the patients fluid and nutritional goals. There is no effective treatment and current management includes total parenteral nutrition ("TPN"), which itself is a source of significant morbidity and mortality. Accordingly, there is a need for an alternative method of management for

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short bowel syndrome. Other disorders of the small intestine can render the bowel nonfunctional for a prolonged period of time such as severe infection and inflammatory bowel disease. It is an object of the present invention to provide an alternative method for management for short bowel syndrome and other disorders of the intestine. Web site: http://www.delphion.com/details?pn=US06630444__ •

Lipoxygenase inhibitors Inventor(s): Allen; Larry M. (Fort Collins, CO) Assignee(s): Chemex Pharmaceuticals (denver, Co) Patent Number: 4,708,964 Date filed: February 9, 1984 Abstract: This invention provides methods of using a number of compounds for the inhibition of lipoxygenase in humans. Pathological conditions which may be treated by the compounds described herein include psoriasis, cellular proliferation, skin allergies, insect bites, allergic rhinitis, conjunctivitis, hay fever, bronchial asthma, allergic gastroenteritis, uterine contractions, hyperactivity of the colon and bronchospasms. Excerpt(s): This application is related to commonly assigned U.S. application Ser. Nos. 578,413, abandoned, for "Tumor Reducing Compositions," Allen, and 578,412, abandoned, "Antioxidant Compounds and Methods of Synthesis," Allen, et al., being filed in the U.S. Patent Office concurrently herewith. The entire contents of those applications are incorporated herein by reference. This invention relates to the use of certain organic compounds as inhibitors of the lipoxygenase pathway of the arachidonic acid. The assignee hereof has filed a number of applications referring to nordihydroguaiaretic acid (NDGA) and related compounds, and also mixtures of such compounds with metal salts, useful for the treatment of psoriasis, namely U.S. application Ser. No. 578, 501, abandoned, "Pharmacologically Active Mixtures of Organic Compositions and Metal Salts," Jordan, a continuation in part of Ser. No. 465,631, abandoned, being filed in the U.S. Patent Office concurrently herewith; U.S. application Ser. No. 578,549 "Methods of Treating Psoriasis and Inhibiting the Action of Lipoxygenase on Arachidonic Acid," Jordan, also being filed concurrently herewith; and U.S. Ser. No. 365,784, "Modification of Plant Extracts from Zygophyllaceae," Jordan. Web site: http://www.delphion.com/details?pn=US04708964__

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Mammalian livestock feed, Mammalian livestock feed additive, and methods for using same Inventor(s): DeRovira; Dorf A. (Branchburg, NJ), Kare; Morley R. (Narberth, PA), Mason; J. Russell (Philadelphia, PA) Assignee(s): Monell Chemistry Senses Center (philadelphia, Pa) Patent Number: 4,790,990 Date filed: July 31, 1986 Abstract: The present application discloses a novel mammalian livestock feed additive containing a selective avian taste aversive agent, preferably dimethyl anthranilate, which is at least partially entrapped in an edible solid vehicle to improve its taste persistency. In the preferred embodiment, the edible vehicle is a modified food starch

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which is spray dried with the avian taste aversive agent. The disclosed livestock feed additive may be incorporated in a livestock feed to reduce the amount of feed lost to avian species, and to reduce the likelihood that mammals will be infected by avian transmitted diseases such as transmissible gastroenteritis. Alternatively, a mammalian poison is disclosed comprising an avian taste aversive additive which will increase the amount of that poison available for ingestion by mammalian target species and decrease the likelihood of secondary poisoning of a number of endangered species. An improved avian poison is also disclosed comprising a mixture of a discrete avian toxicant and a discrete avian food component, comprising an avian taste aversive additive which is at least partially entrapped in a vehicle to improve its taste persistency. Excerpt(s): The present invention relates to the fields of livestock feeds, mammalian poisons and avian poisons, including in particular such feeds and poisons which include effective amounts of materials which are distasteful to avian species. Certain embodiments of the present invention relate to materials and methods for reducing agricultural losses due to certain avian species, such as starlings. The cost of starlings to an individual farmer from consuming livestock feed can vary considerably fromnegligible loss up to several thousand dollars during the fall-winter damage season. Palmer, T. K. 1976, "Pest Bird Damage Control in Cattle Feedlots: The Integrated Systems Approach", Proc. Vertebr. Pest Control Conf., Monterey, Calif. 7:17-21. Generally, the large beef cattle feedlots of the west have the most significant losses. However, moderately sized dairy farms in Tennessee feeding 100 to several hundred head of cattle have been estimated to sustain losses of several hundred dollars during a 3-month damage season. Glahn, J. F., "Blackbird and Starling Depredations at Tennessee Livestock Farms", Proc. Ninth Bird Control Seminar, Bowling Green, Ohio. In Press. Although starlings can be a problem at hog operations, hog producers need not suffer significant feed loss problems with the use and proper adjustment of flip-top feeders and confinement of swine when feeding. In terms of percent feed loss farmers in Tennessee sustained up to 10% loss to birds of the grain component fed to livestock. A similar study in the United Kingdom estimated losses to farmers at up to 12%. Feare, C. J., and K. P. Swannack, "Starling Damage and its Prevention at an Open-Fronted Calf Yard", Anim. Prod. 26:259-265 (1978). Uses of repellents to reduce damage in actual field conditions for protecting costly ($8-12 per hundred weight) high protein feeds from starlings would probably be beneficial if costs of the repellent were below 10% the cost of the feed. This estimate considers only the limited data now available on the maximum cost due to feed loss only. It does not consider other factors such as potential for disease transmission. The distribution and magnitude of feed loss damage on a national scale has not been studied. However, one study in the winter of 1980 inspected 287 livestock farms in 6 selected livestock producing countries in Tennessee. Glahn, J. F. supra. (In press). Results of this study indicated that 26% of the farms had more than a negligible damage problem including 6% with significant problems where losses exceeding $100 per season would be expected. Based on Tennessee Ag Statistics there were 43,000 hog and dairy farms in Tennessee in 1980. However, since the bird damage survey only sampled farms with greater than 20 head of livestock, the authors estimated the sampled population at 25,900 farms. Therefore, the 6% of the farms that could have benefitted from control measures was 1,554. These data are subject to seasonal changes in bird populations, weather conditions, and farm practices, but gives some idea of the number of farms that might benefit from bird control measures. Web site: http://www.delphion.com/details?pn=US04790990__

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Method for immunizing nursing piglets against transmissible gastroenteritis(TGE) virus Inventor(s): Parks; John B. (Mountain View, CA) Assignee(s): Syntex (u.s.a.) Inc. (palo Alto, Ca) Patent Number: 3,962,422 Date filed: February 18, 1975 Abstract: Method for immunizing nursing piglets against transmissible gastroenteritis (TGE) virus by administering to the pregnant sow an effective amount of a vaccine containing attenuated TGE virus and permitting the nursing piglets to suckle the sow. The vaccine is administered twice, (a) intramuscularly at from about 63 days to about 21 days pre-farrowing and (b) intranasally at from about 21 days to about 7 days prefarrowing, with the proviso that at least 14 days and not more than 42 days elapse between the intranasal and intramuscular inoculations. Excerpt(s): This invention relates to a novel method of immunizing nursing piglets against transmissible gastroenteritis (TGE) virus by administering to a pregnant sow an effective amount of a vaccine containing attenuated TGE virus, said vaccine being administered twice, (a) intramuscularly at from about 63 days to about 21 days prefarrowing and (b) intranasally at from about 21 days to about 7 days pre-farrowing, with the proviso that at least 14 days and not more than 42 days elapse between the intranasal and intramuscular inoculations, and permitting said nursing piglets to suckle said sow. Bohl et al., Infection and Immunity, September 6, 1972, p. 289-301 and Saif et al., Infection and Immunity, Oct. 6, 1972, p. 600-609, have reported that (1) there is high mortality in challenged nursing piglets when attenuated strains of TGE virus are administered to pregnant sows intramuscularly and (2) nursing piglets are better protected when virulent TGE virus was orally-intranasally administered to pregnant sows. Abou-Youssef et al., Proceedings of the 75th Annual Meeting of the United States Animal Health Association, 1971, p. 329-341, have reported that nursing piglets were not protected when virulent TGE virus was administered intramuscularly to the pregnant sow; but when virulent TGE virus was administered orally to pregnant sows, the nursing piglets were protected. However, Stone et al., American Journal of Veterinary Research, 35, Mar. 3, l974, p. 339-345, have reported that pregnant sows inoculated either orally or intramuscularly with virulent TGE virus afforded protection to the nursing piglets. Thus, it will be seen that there is disagreement in the art regarding both the type of virus (virulent or attenuated ) to be administered and the mode of administration. This invention relates to a method for the immunization of nursing piglets against transmissible gastroenteritis (TGE). More particularly it relates to a method for imparting immunity to nursing piglets against TGE virus by vaccinating the pregnant sow, the dam, twice (a) intramuscularly from about 63 days to about 21 days pre-farrowing and (b) intranasally from about 21 days to about 7 days pre-farrowing, with the proviso that at least 14 days and not more than 42 days elapse between the intranasal and intramuscular inoculations, and permitting said nursing piglets to suckle their dam. Web site: http://www.delphion.com/details?pn=US03962422__

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Method for preventing diarrhea Inventor(s): Ebina; Takusaburo (Sendai, JP) Assignee(s): Mitsubishi Kasei Corporation (tokyo, Jp), Sendai Institute of Microbiology (sendai, Jp) Patent Number: 5,143,727 Date filed: August 29, 1988 Abstract: A therapeutic agent which is milk collected from a milk animal which has been immunized by a virus or viruses capable of growing in the digestive tract can be used to prevent a disease such as intractable diseases including multiple sclerosis, acute gastroenteritis and viral hepatitis, which are caused by said virus. Excerpt(s): The present invention relates to a therapeutic method, more particularly, to a therapeutic method for diseases such as intractable diseases including multiple sclerosis, acute gastroenteritis, viral hepatitis and the like, which are caused by virus capable of growing in the digestive tract. Heretofore, no effective preventive method has been found for intractable neuropathic diseases such as multiple sclerosis, Bechet disease, myasthenia gravis, amyotrophic lateral sclerosis, systemic lupus erythematosus, Parkinson disease, and slow virus infection disease. Corticosteroids such as Prednisolone are only examples which have been practically used. However, they are accompanied by strong side effects. As a result of a long term virological and immunological study on the above-described diseases, it has now been found that these intractable diseases are autoimmune diseases triggered by virus infections and, to prevent such diseases, it is only necessary to avoid the growth of respective virus in a digestive tract. It has also been found that, when a milk animal such as cow or goat, preferably in her pregnancy, is immunized by viruses, lots of anti-virus antibody are contained in the milk, particularly, colostrum and, upon oral administration of the milk such intractable disease or diseases can be considerably prevented. Web site: http://www.delphion.com/details?pn=US05143727__

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Method of preparing an attenuated transmissible gastroenteritis (TGE) virus strain for use in live vaccines Inventor(s): Bachmann; Peter A. (Veterinar-Str. 13, 8000 Munich 22, DE), Mayr; Anton (Veterinar-Str. 13, 8000 Munich 22, DE) Assignee(s): None Reported Patent Number: 4,159,319 Date filed: April 19, 1978 Abstract: The invention relates to a method of preparing an attenuated virus strain, which can be used to protect pigs, and in particular piglets, against transmissible gastroenteritis (TGE). Excerpt(s): The disease TGE is nearly always fatal for piglets which are infected in the first few weeks after birth. Since active immunization is not yet possible at such an instant within that period, it has been endeavoured for some time already to find a method to provide a passive immunity to piglets through the sow. Although a few methods are known for giving piglets a passive immunity through the colostrum of the mother animal (Belgian Patent Specification No. 669,881 and Netherlands Patent Application No. 68.09013), it is known from recent literature that passive immunity in

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piglets can be produced by oral infection of the sow with field strains of the TGE (that is to say with virulent virus), but attempts to produce this with virus strains attenuated by cell culture passages have failed or have given only a restricted degree of protection (Infection and Immunity, 1976 pp. 1642-1646). This is because by the use of serial passages not only the virulence but also the immunogenicity decrease considerably. Since the administration of virulent virus to sows involves great risks, this is an undesired and unacceptable method of protecting piglets against TGE. Web site: http://www.delphion.com/details?pn=US04159319__ •

Method of treating inflammatory conditions with progesterone analogs Inventor(s): Schreiber; Alan D. (Philadelphia, PA) Assignee(s): University of Pennsylvania (philadelphia, Pa) Patent Number: 6,610,674 Date filed: September 8, 2000 Abstract: The present invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis, using progesterone or progesterone analogs such as medroxyprogesterone acetate. Excerpt(s): This invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis using progesterone and progesterone analogs. Proctitis, inflammation of the rectum, is invariably present in UC and is sometimes present in CD. It may also occur independently from these diseases. Proctitis is another manifestation of IBD with pathology similar to UC. A patient presenting with proctitis may later develop fullblown UC or CD. Physicians and medical researchers have not been successful in identifying a cause for these diseases, although several theories have been postulated. The diseases may be caused by a pathogen or other antigen that initiates the inflammatory response in the bowel, accompanied by a defect in the ability to downregulate the immune response. Once initiated, many of the pathophysiological events in IBD are related to amplification of the inflammatory process. In response to antigens, cytokines and other inflammatory mediators are released. Some cytokines promote T cell activity. The inflammatory cascade continues with IL-2, helper T cells, B-cell proliferation, and antibody synthesis. Stimulated neutrophils and macrophages accumulate and further damage the tissue by releasing reactive oxygen species and other biologically active products. Additional acute inflammatory cells respond to the tissue damage, whether or not the primary initiating stimulus has ceased. Web site: http://www.delphion.com/details?pn=US06610674__

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Pathogenic porcine respiratory coronavirus Inventor(s): Halbur; Patrick G. (Ames, IA), Paul; Prem S. (Ames, IA), Vaughn; Eric M. (Ames, IA) Assignee(s): Iowa State University Research Foundation, Inc. (ames, Ia) Patent Number: 5,419,907 Date filed: November 10, 1992 Abstract: The present invention provides a biologically pure culture of a novel pathogenic porcine respiratory coronavirus (PRCV) and a vaccine derived therefrom effective against PRCV infection and transmissible gastroenteritis virus (TGEV) infection. Excerpt(s): Transmissible gastroenteritis virus (TGEV) causes a fatal diarrheal disease in neonatal piglets because it selectively infects and destroys the small-intestinal enterocytes required for nutrient absorption and fluid regulation (H. W. Moon, J. Am. Vet. Med. Assoc., 172, 443 (1978)). Additionally, TGEV replicates in porcine respiratory tract tissues but this does not result in primary respiratory disease (L. J. Kemeny et al., Cornell Vet., 65, 352 (1975)). A new porcine respiratory coronavirus, tentatively designated PRCV, which has a close antigenic relationship to TGEV, suddenly emerged in 1983 to 1984 and spread within less than 2 years in most if not all European countries, where it now persists enzootically. A cytopathic agent has been isolated in cell culture and pathogenesis studies have shown that it replicated at a high titre in the respiratory tract, but to a very low extent in the gut (M. Pensaert et al., Veterinary Quarterly, 8, 257 (1986)). Conventional serological tests do not distinguish between PRCV- and TGEVinfected animals. However, antigenic dissimilarities were evident on examining the heterologous reactivity of monoclonal antibodies (MAbs). PRCV was found to be nonreactive towards several non-neutralizing anti-TGEV MAbs directed against the S (spike) or M (membrane) proteins (P. Callebaut et al., J. Gen. Virol., 69, 1725 (1988); J. Garwes et al., Veterinary Record, 122, 86 (1988)). Neutralization-mediating epitopes unique to TGEV have been identified also, e.g., by H. Laude et al., Journees de la Recherche Porcine en France, 20, 89 (1988). Conversely, anti-PRCV S-specific MAbs have been shown to differentiate between the two viruses. Web site: http://www.delphion.com/details?pn=US05419907__

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Specific antigen vaccine for TGE in swine Inventor(s): Gough; Patricia M. (Ames, IA) Assignee(s): Iowa State University Research Foundation, Inc. (ames, Ia) Patent Number: 4,335,105 Date filed: May 11, 1981 Abstract: A vaccine for protecting swine against transmissible gastroenteritis (TGE) is prepared from a specific antigenic protein (SPA) obtained by separation from TGE virus. The SPA is characterized by a buoyant density of 1.02 to 1.03 gms/ml in a solution of sucrose. The vaccine may be prepared in parenteral dose form for administration to pregnant sows, thereby effectively protecting the baby pigs against fatal TGE infection. Excerpt(s): Transmissible gastroenteritis (TGE) of swine is caused by a coronavirus (TGEV). The disease occures wherever swine are raised, and it is highly fatal for baby pigs during the first few weeks after farrowing. However, if the sow has had a recent

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TGE infection, protective antibodies are transferred to the offspring in the colostrum and milk which protect the baby pigs against TGE. Bohl et al, Infect. & Immun., 6, 289-230 (1972). TGE vaccines have been developed which are capable of producing high serum virus neutralizing titers to TGEV. Such vaccines are prepared from attenuated, nonvirulent TGEV, strains of which may be prepared by continuous cell culture of virulent TGEV. See, for example, U.S. Pat. Nos. 3,479,430 and 3,585,108. However, such vaccines are not very effective in producing lactogenic immunity in the sow, whether the attenuated TGEV is given live or inactivated. Tamoglia, J.A.V.M.A., 160, 554-558 (1972). Studies have shown that IgA antibodies are produced in milk by TGE infection or by administration of live virulent TGEV, while the administration of attenuated vaccines produces mainly IgG antibodies. Bohl et al, Infect. & Immun., 11, 23-32 (1975). Bohl et al suggest that effective passive immunization of baby pigs may depend on continual neutralization of virus within their intestinal tracts by the IgA antibodies produced in milk after exposure of the sow to virulent TGE. However, vaccines containing virulent TGEV would be hazardous to use, since the virus is readily transferred among swine in a herd. Coronaviruses have been reported as containing from four to sixteen different proteins, which are in the form of polypeptides, some of which are glycosylated. Wege et al, J. Gen. Virol., 42, 37-47 (1979). For example, Wege et al analyzed the proteins of the murine coronavirus and found that it contained six proteins, two of which were glycoproteins, and that the protein components ranged in molecular weight from about 170,000 to 22,700. A preliminary report on the purification and fractionation of the proteins of TGE virus was presented by Gough and Ellis to the 1976 Conference of Research Workers in Animal Disease at Chicago, Ill. An Abstract of the Gough and Ellis paper was published: Abstracts of Papers Presented at Conference of Research Workers in Animal Disease, 57th Annual Meeting Nov. 29-30, 1976, p. 11. The discoveries on which the present invention are based occurred subsequent to 1976, which were not made public prior to the filing of this application. Web site: http://www.delphion.com/details?pn=US04335105__ •

Transmissible gastroenteritis virus genes Inventor(s): Brian; David A. (Knoxville, TN), Kapke; Paul A. (Ames, IA) Assignee(s): University of Tennessee (knoxville, Tn) Patent Number: 5,202,430 Date filed: January 10, 1991 Abstract: The present invention provides recombinant DNA molecules comprising a sequence encoding a transmissible gastroenteritis virus polypeptide selected from the group consisting of M, N and P, host cells transformed by said recombinant DNA molecule sequences, the M, N and P polypeptides. The present invention also provides subunit vaccines for TGEV. Excerpt(s): This invention relates to recombinant DNA. More specifically, the invention relates to DNA sequences encoding transmissible gastroenteritis virus proteins and polypeptides related thereto. These DNA sequences are useful fro screening animals to determine whether they are infected with transmissible gastroenteritis virus and also for expressing the polypeptides encoded thereby. Transmissible gastroenteritis virus (TGEV) is a highly contagious, enteric disease of swine characterized by vomiting, severe diarrhea, and a high mortality in piglets under two weeks old. Although swine of all ages are susceptible to TGEV, the mortality rate in swine over five weeks old is very low. The first reported occurrence of TGEV in the United States was in 1945. Subsequent

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to its recognition in the United States, TGEV has been reported in Japan, England, many European countries, Taiwan. Central and South America and Canada. Web site: http://www.delphion.com/details?pn=US05202430__ •

Treatment of diarrhea Inventor(s): Casas; Ivan A. (Raleigh, NC), Mollstam; Bo (Lerum, SE) Assignee(s): Biogaia Biologics AB (stockholm, Se) Patent Number: 5,837,238 Date filed: June 5, 1996 Abstract: A therapeutic method of treating diarrhea of a patient, such as that caused by rotavirus in which a liquid suspension of one or more strains of Lactobacillus reuteni is administered to the patient. Preferably the L. reuteri is isolated from an animal of the same species as the animal to which the therapy is being given. Preferably at least about 10.sup.7 cells of L. reuteri, and most preferably, at least 10.sup.8 cells, are administrated per day, over a period of one to seven days, depending on the severity of the gastroenteritis. The result is a rapid, dramatic reduction in animal's diarrhea and vomiting, previously not found using other therapies. Excerpt(s): This invention relates to therapeutic treatment of infectious gastroenteritis. Normal microflora is important in the protection of the host against diseases of the gastrointestinal (GI) tract (Fuller, R., Gut 1991;32:439-42; Salminen, S. et al., Dig Dis Sci 1992;10:227-38). During periods of acute diarrhea, the normal gastrointestinal microflora is radically changed. These changes include decreasing numbers of Lactobacilli, Bacteroides and Bifidobacteria (Saiminen S. et al., Dig Dis Sci 1992;10:227-38; Tazume S. et al., Clin Infect Dis 1993;16(2 suppl):77-82S; Mitsuoka T., in Wood B J B, London:Elsevier Applied Science 1992, 1:69-114; Salminen S. et al., Chemotherapy, in press.). Lactobacillus reuteri is the most commonly occurring Lactobacillus species found in the GI tract of humans and animals (Kandler O. et al., Zbl Bakt Abt Orig 1980; C1:264-9). Like other Lactobacilli, L. reuteri produces acidic metabolic end-products (lactic and acetic acids) which have considerable antimicrobial activity (Axelson L. T. et al., Microb Ecology Health Dis 1989;2: 131-6). Use of L. reuteri cell therapy for other than probiotic purposes, i.e., benefitting the host by improving the indigenous microflora, or antibiotic purposes, is not known. Web site: http://www.delphion.com/details?pn=US05837238__

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Vaccine based on TGEV for protection of dogs against canine coronavirus Inventor(s): Bordt; Dale (White Hall, IL), Draayer; Hans (White Hall, IL) Assignee(s): Pfizer, Inc. (new York, Ny) Patent Number: 5,911,999 Date filed: March 27, 1991 Abstract: A method for preventing canine coronavirus in dogs is disclosed which comprises administering to a dog a live or inactivated vaccine prepared from transmissible gastroenteritis virus of swine (a TGEV vaccine). An inactivated vaccine composition for use in such a method and a process for the manufacture of the inactivated vaccine composition are described.

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Excerpt(s): This invention relates to vaccines and in particular to vaccines which are useful in protecting dogs against canine coronavirus. The coronaviruses were first recognised and morphologically defined as a group by Tyrrell and co-workers. A comprehensive review of the biology and pathogenesis of coronaviruses has been published by H. Wege et al., Current Topics in Microbial Immunology, 1982, 99, 165-200. Canine coronavirus (CCV) was first isolated in 1971, and has increasingly become a problem, particularly amongst puppies and in kennel-raised dogs. It produces a mild to moderate diarrhea, often preceded by lethargy, depression and lack of appetite. Dehydration and subsequent weight loss generally follow. Although the disease is generally not fatal, it is felt that few puppies achieve their full vitality following the infection. Web site: http://www.delphion.com/details?pn=US05911999__

Patent Applications on Gastroenteritis 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 gastroenteritis: •

Expression cassetts and methods for delivery of animal vaccines Inventor(s): All, Benjamin P.; (Johnston, IA), Howard, John A.; (College Station, TX) Correspondence: Zarley Mckee Thomte Voorhees & Sease Plc; Suite 3200; 801 Grand Avenue; Des Moines; IA; 50309-2721; US Patent Application Number: 20020058312 Date filed: March 1, 2001 Abstract: The present invention provides an expression cassette for expressing vaccine antigens in a plant cell. The expression cassette includes a DNA sequence which encodes for at least one vaccine antigen which is operably linked to transcriptional and translational control regions functional in the plant cell. The vaccine antigens of the invention are useful for protection of an animal against mucosal diseases such as Transmissible Gastroenteritis Virus (TGEV) and rotavirus. The invention also provides a transgenic plant and transgenic plant seed which has been stably transformed to express a vaccine antigen which is included in an expression cassette of the invention. The transformed plant and plant cells may be from monocot or dicot plants and include, for example, corn, soybeans, sunflower, canola or alfalfa.The transgenic plants and plant seeds of the invention may be used as a feed composition for animals. Alternatively, the transgenic plant and plant seeds of the invention may provide an immunogenic composition for protecting animals against mucosal diseases after oral administration. Excerpt(s): Diseases of the mucosal tissue, such as those affecting the enteric system, the respiratory tract, urogenital tract and mammary glands are of significant economic impact in domestic animals. These diseases include, for example, the Bovine Respiratory Disease Complex (BRDC), bovine and porcine rotavirus and coronavirus, bacterial pathogens such as Pasteurella spp. and Haemophilus spp., mastitis in dairy cattle and abortion-inducing pathogens such as Leptospira spp. and Campylobacter fetus. Mucosal

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

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immunity is of prime importance in protection against these diseases. Secretory IgA (SIgA) is the predominant immunoglobulin relevant to the prevention of infection of mucosal surfaces. The main protective function of SIgA antibodies is the "immune exclusion" of bacterial and viral pathogens, bacterial toxins and other antigens. The immune response generated at the surface of one mucosal tissue site can be disseminated to other mucosal sites due to the migration of lymphocytes to other mucosal tissue, thus providing immunity at all mucosal tissue sites. Once mucosal immunity is established in an animal it can be advantageously transferred to the offspring. Immunity in neonates may be passively acquired through colostrum and/or milk. This has been referred to as lactogenic immunity and is an efficient way to protect animals during early life. SIgA is the major immunoglobulin in milk and is most efficiently induced by mucosal immunization. It is now widely recognized that mucosal immunity is generally best induced by direct immunization of the mucosal tissue. In order to enhance efficacy against mucosal diseases, vaccines should stimulate the mucosal system and generate an SIgA immune response. One way of achieving this goal is by administering the vaccine orally and targeting the mucosal tissue lining the gastrointestinal tract. Studies support the potential of inducing SIgA antibody formation and immune protection in "distant" extra-intestinal mucosal sites after oral vaccination. Activated lymphocytes from the gut can disseminate immunity to other mucosal and glandular tissues. Therefore, oral vaccines can protect against infections at sites remote from the antigenic stimulation, for example in the respiratory and urogenital tracts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of treating inflammatory conditions with progesterone or progesterone analogs Inventor(s): Schreiber, Alan D.; (Philadelphia, PA) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040038954 Date filed: June 24, 2003 Abstract: The present invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis, using progesterone or progesterone analogs such as medroxyprogesterone acetate. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/156,434, filed Sep. 28, 1999. This invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis using progesterone and progesterone analogs. "Inflammatory bowel disease" (IBD) encompasses the idiopathic, chronic inflammatory bowel diseases ulcerative colitis (UC), Crohn's disease (CD), and proctitis. Researchers do not know the cause of these diseases, but believe that they involve genetic and immunologic influences on the gastrointestinal tract's ability to distinguish foreign from self-antigens and/or to alter the mucosal immune response. They share many overlapping

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epidemiological, clinical, and therapeutic features IBD affects up to 1,000,000 Americans and disease symptoms can be so severe as to prevent the patient from carrying on a normal life. The total cost of the disease, including lost productivity, in the US is two billion dollars per year. Ward et al., Clinical economics review: medical management of inflammatory bowel disease; Ailment Pharmacol Ther 13:15-25 (1999). Drug therapies that allow patients to avoid surgical intervention could reduce the cost significantly. 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 gastroenteritis, 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 “gastroenteritis” (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 gastroenteritis. You can also use this procedure to view pending patent applications concerning gastroenteritis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON GASTROENTERITIS Overview This chapter provides bibliographic book references relating to gastroenteritis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on gastroenteritis include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

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

PDR for Herbal Medicines. 1st ed Source: Montvale, NJ: Medical Economics Company. 1998. 1244 p. Contact: Available from Medical Economics Publishing Inc. P.O. Box 10689, Des Moines, IA 50336. (800) 922-0937. Fax (515) 284-6714. Website: www.medecbookstore.com. PRICE: $59.99. ISBN: 1563632926. Summary: Most of today's herbal remedies exhibit varying degrees of therapeutic value. Some, such as ginkgo, valerian, and saw palmetto, seem genuinely useful, while others, such as ephedra, tansy, and nightshade, can actually be dangerous. As the use of unfamiliar botanicals spreads, the need to steer patients toward the few truly useful preparations and warn them away from ineffective, dangerous alternatives is becoming an increasingly significant priority. This volume, from the publishers of Physicians Desk Reference, brings together the findings of the German Regulatory Authority's herbal

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watchdog agency (commonly caused Commission E). This agency conducted an intensive assessment of the peer-reviewed literature on some 300 common botanicals, weighing the quality of the clinical evidence and identifying the uses for which the herb can reasonably be considered effective. This reference book contains profiles of over 600 medicinal herbs. Each entry contains up to 9 standard sections: name(s), description, actions and pharmacology, indications and usage, contraindications, precautions and adverse reactions, overdosage, dosage, and literature. The entries have also been indexed by scientific and common name, indications, therapeutic category, and side effects. To assist in identification, the reference book includes a section of full-color plates of the plants included. The book concludes with a glossary of the specialized botanical nomenclature and other unfamiliar terminology, a list of poison control centers, and a list of drug information centers. Some of the herbs are listed for use for abdominal cramps or distress, acid indigestion, appetite stimulation, rectal bleeding, various bowel disorders, stomach cancer, cholelithiasis (gallstones), colic, colitis, constipation, dehydration, diarrhea, digestive disorders, dysentery, enteritis, anal fissure, flatulence (intestinal gas), gastritis, gastroenteritis, gastrointestinal disorders, gout, helminthiasis, hemorrhage, hemorrhoids, hepatitis, hypercholesterolemia, jaundice, liver and gall bladder complaints, liver disorders, malaria, nausea, abdominal pain, and vomiting. •

Diseases of the Small Intestine in Childhood. 4th ed Source: Oxford, UK: Isis Medical Media, Ltd. 1999. 412 p. Contact: Available from Isis Medical Media, Ltd. 59 St. Aldates, Oxford, OX1 1ST, UK. 01865 202939. Fax 01865 202940. E-mail: [email protected]. Website: www.isismedical.com. PRICE: $99.00 plus shipping and handling. Summary: The small intestine is the principal organ of absorption in the human body, and complete resection of the small intestine is not compatible with life. It is thus considered a vital organ whose continuing healthy function is a major determinant of the good health and normal development of the growing infant and child. This textbook reviews diseases of the small intestine in childhood, with emphasis on a discussion of their causes, clinical manifestations, newer techniques used in diagnosis, and modern methods of patient management, notably diet therapy. The text offers 17 chapters: the architecture and matrix of the small intestine, enterocyte proliferation and functions, the immune system of the small intestine, mechanisms of malabsorption and secretion, clinical and laboratory assessment (diagnostic tests), gastroenteritis and its sequelae, parasitic infections, gastrointestinal food allergy, celiac disease, intractable diarrhea, Crohn's disease and abdominal tuberculosis, surgically correctable lesions of the small intestine, necrotizing enterocolitis, short bowel syndrome and small intestinal transplantation, disorders of small intestinal motility, and miscellaneous disorders of the small intestine. Each chapter offers full color photographs and diagrams, and concludes with extensive references. One appendix reviews special milks; a subject index concludes the volume.

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Medical Advisor Home Edition: The Complete Guide to Alternative and Conventional Treatments Source: Alexandria, VA: Time-Life Books. 1997. 960 p. Contact: Available from Time-Life Books. 400 Keystone Industrial Park, Dunsmore, PA 18512. PRICE: $20.00. ISBN: 0783552505.

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Summary: This book offers information about 300 health problems, ranging from relatively benign conditions to the most serious diseases. There are symptoms charts which name several related problems and help readers decide which ailment entry to look up. Ailment entries provide a more complete list of symptoms, plus guidelines to discern whether the condition is potentially serious or requires a doctor's attention. Each entry describes the ailment and how it affects the body. Next, the entry outlines the underlying causes of the ailment and the tests and procedures a doctor may use to confirm the diagnosis. The treatment segment presents conventional and alternative recommendations for curing the problem or alleviating the symptoms. Most ailment entries conclude with advice on preventive measures that can be used to maintain health. Alternative treatments discussed include bodywork, acupuncture and acupressure, herbal therapies, homeopathy, lifestyle changes, and nutrition and diet. The book begins with a section on emergency medicine. Also included is a visual diagnostic guide, an atlas to the body, a medicine chest section (describing herbs, homeopathic remedies, and over the counter drugs), a glossary, a subject index, a bibliography, and a list of health associations and organizations. Topics related to digestive diseases include abdominal pain, AIDS, allergies, anal bleeding, anal fissure, anorexia nervosa, bad breath, bowel movement abnormalities, bulimia, celiac disease, cholesterol problems, colitis, colorectal cancer, constipation, Crohn's disease, diarrhea, diverticulitis, flu, food poisoning, gallstones, gas and gas pains, gastritis, gastroenteritis, heartburn, hiatal hernia, hiccups, incontinence, indigestion, irritable bowel syndrome, lactose intolerance, lupus, obesity, pancreatic cancer, pancreatic problems, stomach cancer, stomach ulcers, swallowing difficulty, trichomoniasis, vomiting, and worms. The book is illustrated with line drawings and full-color photographs. •

Understanding Indigestion and Other Tummy Troubles Source: Woollahra, New South Wales, Australia: Health Books, Gore and Osment Publications. 1993. 64 p. Contact: Available from Health Books, Gore and Osment Publications, Private Box 427, 150 Queen Street, Woollahra, NSW 2025, Australia. (02) 361-5244. Fax (02) 360-7558. PRICE: $9.95 (as of 1995). ISBN: 187553136X. Summary: This book presents basic information on the causes and treatments of common stomach and digestive tract ailments. After an introductory section that reviews the anatomy and physiology of the gastrointestinal (GI) tract, the book features nine chapters on the following topics: indigestion; ulcers; food poisoning and other causes of upset stomachs and diarrhea; irritable bowel syndrome (IBS); inflammatory bowel disease (IBD); dealing with diverticular disease; bowel cancer; other GI problems, including hiccups, gas, hepatitis, food allergies, appendicitis, and sexually transmitted diseases of the bowel; and children's GI problems, including colic, food intolerance, gastroenteritis, reflux, celiac disease, constipation, IBS, IBD, polyps, and phantom pains. The book is written in clear, easy-to-understand language and focuses on practical, selfcare tips for many of the disorders covered.

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Clinical Practice of Gastroenterology. Volume One Source: Philadelphia, PA: Current Medicine. 1999. 783 p. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2).

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Summary: This lengthy textbook brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. This first volume includes 86 chapters in four sections: esophagus, stomach and duodenum, small bowel, and colon. Specific topics include normal esophageal physiology, gastroesophageal reflux disease (GERD), motor disorders of the esophagus, esophageal foreign bodies, esophagitis, esophageal trauma, esophageal surgery, gastric and duodenal histology and histopathology, gastroduodenal motility and motility disorders, abdominal pain, nausea and vomiting, dyspepsia (heartburn), Helicobacter pylori, gastric and duodenal ulcer, gastric cancer, gastric infection, gastric surgery, small intestine anatomy and physiology, symptoms and signs of small bowel disease, maldigestion and malabsorption, intestinal obstruction and pseudoobstruction, immunologic disorders, small intestinal malignancies (cancer), short bowel syndrome, Whipple's disease, infectious diarrhea, parasitic diseases of the small intestine, foodborne diseases of the small intestine, gastroenteritis, Crohn's disease, anatomy and physiology of the colon, irritable bowel syndrome (IBS), secretory diarrhea, constipation and fecal impaction, fecal incontinence, gas and flatulence, gastrointestinal bleeding, colitis (including ulcerative colitis), diverticulitis and diverticular hemorrhage, appendicitis, benign tumors of the colon and polyposis syndrome, malignant tumors of the colon, and anorectal disorders. The chapters include figures, algorithms, charts, graphs, radiographs, endoscopic pictures, intraoperative photographs, photomicrographs, tables, and extensive references. The volume concludes with a detailed subject index and a section of color plates. •

Foods That Harm, Foods That Heal: An A-Z Guide to Safe and Healthy Eating Source: Pleasantville, NY: Reader's Digest. 1997. 400 p. Contact: Available from Customer Service, Reader's Digest. Pleasantville, NY 10570. (800) 846-2100. PRICE: $30.00. ISBN: 0895779129. Summary: This nutrition reference book features more than 400 photographs and illustrations with more than 400 A to Z entries on a vast range of foods and health concerns, include caffeine, cancer, diabetes, fast food, garlic, heart disease, influenza, osteoporosis, pregnancy, sexually transmitted diseases, and vegetarianism. The book is designed to provide families with information to help understand the close links between foods and wellness. Each food entry provides at-a-glance information on its nutrients (or lack of) and its benefits and drawbacks. Each ailment is accompanied by a list of foods and beverages that are considered safe, and what foods or beverages should be cut down or avoided altogether. Personalized case studies help to illustrate various topics. There are special features on eating during different life stages, from infancy to old age, as well as such issues as genetically altered foods, irradiation, pesticides, and pollution. Other topics include how to cook foods to achieve maximum nutritional benefits; which dietary supplements really work; tips on exercising, storing food, and reading food labels; an instructive analysis of the most popular diet regimens; and controversial foods and additives such as eggs, nitrites, bran, cheese, milk, fat, wine, and alcohol. A glossary defines unfamiliar or technical terms; there is also a listing of organizations that can provide further information and resources. Topics specifically related to digestive diseases include allergic reactions to food, anorexia nervosa, antioxidants, appetite loss, basic food groups, carbohydrates, celiac disease, childhood and adolescent nutrition, cholesterol, constipation, convenience foods, Crohn's disease, diarrhea, dieting and weight control, digestive and malabsorption disorders, diverticulitis, fats, fiber, food poisoning, gastritis, gastroenteritis, gout, hiatal hernia, indigestion and heartburn, intolerance to milk and other foods, irritable bowel

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syndrome, malnutrition, medicine-food interactions, minerals, obesity, organic and health foods, preparation and storage of food, restaurants and eating out, smoking and diet, sports nutrition, supplements, traveler's health, ulcers, vitamins, and worms and other parasites. •

A-Z Reference Book of Childhood Conditions Source: San Diego, CA: Singular Publishing Group, Inc. 1995. 200 p. Contact: Available from Singular Publishing Group, Inc. 401 West A Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. PRICE: $44.75. ISBN: 156593332x. Summary: This reference book is designed as a quick, ready reference for parents, caregivers, and teachers who may need to deal with unexpected medical events with children. The author stresses that, in addition to knowledge of emergency treatment for a variety of conditions, knowledge of prevention and the spread of infectious disease, as well as the natural history of the illness, is very valuable. After an introductory section outlining the special features of children's disease, the author provides information on 44 conditions, including appendicitis, celiac disease, constipation, and gastroenteritis. The book also includes a glossary of terms and a subject index. (AA-M).

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 “gastroenteritis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “gastroenteritis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “gastroenteritis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Acute gastroenteritis in children : symposium proceedings, December 1-3, 1989, Dorado, Puerto Rico; ISBN: 0444013989; http://www.amazon.com/exec/obidos/ASIN/0444013989/icongroupinterna

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Atlas of Infectious Diseases: Intraabdominal Infections, Hepatitis, and Gastroenteritis (Atlas of Infectious Diseases) by B. Lorber (Editor); ISBN: 1878132474; http://www.amazon.com/exec/obidos/ASIN/1878132474/icongroupinterna

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Atlas of Infectious Diseases: Intra-Abdominal Infections, Hepatitis, and Gastroenteritis (Atlas of Infectious Diseases, Vol 7) by Gerald L. Mandell (Editor), Bennett Lorber (Editor); ISBN: 0443077304; http://www.amazon.com/exec/obidos/ASIN/0443077304/icongroupinterna

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Gastroenteritis Viruses by Novartis Foundation Symposium (Author); ISBN: 0471496634; http://www.amazon.com/exec/obidos/ASIN/0471496634/icongroupinterna

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Intra-Abdominal Infections, Hepatitis, and Gastroenteritis (WINDOWS/MACINTOSH CD-ROM) by Mandell, Bennett Lorber; ISBN: 0443078769; http://www.amazon.com/exec/obidos/ASIN/0443078769/icongroupinterna

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Viral Gastroenteritis (Archives of Virology. Supplementum, 12) by Shunzo Chiba (Editor), Sapporo International Symposium on Viral Gastroenteritis; ISBN: 3211828753; http://www.amazon.com/exec/obidos/ASIN/3211828753/icongroupinterna

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Viral Gastroenteritis (Perspectives in Medical Virology) by Ulrich Desselberger (Editor), James Gray (Editor) (2003); ISBN: 0444514449; http://www.amazon.com/exec/obidos/ASIN/0444514449/icongroupinterna

Chapters on Gastroenteritis In order to find chapters that specifically relate to gastroenteritis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and gastroenteritis 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 “gastroenteritis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on gastroenteritis: •

Eosinophilic Gastroenteritis Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1972-1982. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Eosinophilic gastroenteritis is a disease characterized by tissue eosinophilia (an increase in a type of white blood cells) that can involve any layer or layers of the gut wall. This chapter on eosinophilic gastroenteritis is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include definition and incidence; pathogenesis; classification and clinical features; diagnostic considerations; differential diagnosis; treatment options, including diet, antihelminthics, sodium cromoglycate, glucocorticoids and immunosuppressive agents, and surgery; and prognosis. The chapter includes a mini-outline with page citations, illustrations, and extensive references. 4 figures. 1 table. 100 references.

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Escherichia Coli O157:H7 Gastroenteritis and the Hemolytic Uremic Syndrome: An Emerging Infectious Disease Source: in Coggins, C.H., ed. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 50. Palo Alto, CA: Annual Reviews. 1999. p. 355-367. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org. PRICE: $60.00 plus shipping and handling. ISBN: 0824305507. Summary: Escherichia coli O157:H7 is an increasingly common cause of a variety of illnesses, including blood diarrhea and the hemolytic uremic syndrome (HUS). This emerging infectious agent was first identified in 1982 and has been isolated with

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increasing frequency since then. This article reviews the epidemiology, clinical spectrum, diagnosis, treatment, and prevention of infections with E. coli O157:H7. Infection with E. coli O157:H7 can be entirely asymptomatic or can present with a wide variety of clinical findings, including watery diarrhea, bloody diarrhea, HUS, thrombotic thrombocytopenic purpura (TTP), and death. The illness usually resolves after 1 week with no obvious sequelae; however, 5 to 10 percent of children with E. coli O157:H7 infection will develop HUS. HUS consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and oliguric renal failure. Antimicrobial agents have no proven value in the treatment of E. coli O157:H7 infections. Antimotility agents should not be given to patients with bloody diarrhea or suspected E. coli O157:H7 infection, as these drugs may increase the risk of HUS in these patients. Treatment of HUS is supportive, with particular attention to the management of fluids and electrolytes. With meticulous care, the mortality rate for HUS is approximately 4 percent. 1 figure. 62 references. (AA-M). •

Technical Report Summary: Acute Gastroenteritis Source: in American Academy of Pediatric. Pediatric Clinical Practice Guidelines and Policies: A Compendium of Evidence-based Research for Pediatric Practice. Elk Grove Village, IL: American Academy of Pediatrics. 2001. p. 195-201. Contact: Available from American Academy of Pediatrics. P.O. Box 927, 141 Northwest Point Boulevard, Elk Grove Village, IL 60009-0927. (800) 433-9016. PRICE: $47.95 (members) plus $6.25 shipping and handling; $52.95 for nonmembers; plus $8.95 shipping and handling. ISBN: 1581100701. Summary: The practice parameter on acute gastroenteritis (published concomitantly in this journal) is intended to present current knowledge about the optimal treatment of children with diarrhea. This technical report details the process followed in the development of the practice parameter, and presents the evidence used to formulate the final recommendations. The authors describe the development of the evidence model, the literature review, article selection, statistical methods, recommendations and level of evidence. Three areas were considered: oral rehydration therapy versus intravenous therapy; early refeeding; and drug therapy for diarrhea. Conclusions were that oral rehydration therapy (ORT) is recommended as the preferred treatment of fluid and electrolyte losses due to diarrhea in children with mild to moderate dehydration. Appropriate diets are recommended during an episode of diarrhea as soon as rehydration has been achieved. Drug agents are not recommended to treat acute childhood diarrhea.

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Practice Parameter: The Management of Acute Gastroenteritis in Young Children Source: in American Academy of Pediatrics. Clinical Practice Guidelines of the American Academy of Pediatrics: A Compendium [Compilation] of Evidence-Based Research for Pediatric Practice. Elk Grove Village, IL: American Academy of Pediatrics. 1999. p. 119-146. Contact: Available from American Academy of Pediatrics. P.O. Box 747, Elk Grove Village, IL 60009-0747. (800) 433-9016 or (947) 228-5005. Fax (847) 228-1281. PRICE: $39.95 for members; $44.95 for nonmembers. ISBN: 1581100264. Summary: This Clinical Practice Guideline from the American Academy of Pediatrics offers recommendations for the management of acute diarrhea in children ages 1 month to 5 years. Three specific management issues are considered: methods of rehydration, refeeding after rehydration, and the use of antidiarrheal agents. Main outcomes

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considered by the subcommittee that created the Guideline were success or failure of rehydration, resolution of diarrhea, and adverse effects from various treatment options. Oral rehydration was found to be as effective as intravenous therapy in rehydrating children with mild to moderate dehydration and is the therapy of first choice in these patients. Early refeeding with milk or food after rehydration does not prolong diarrhea; there is evidence that it may reduce the duration of diarrhea by approximately half a day and is recommended to restore nutritional balance as soon as possible. Data on antidiarrheal agents were not sufficient to demonstrate efficacy; therefore, the routine use of antidiarrheal agents is not recommended, because many of these agents have potentially serious adverse effects in infants and young children. The chapter includes an algorithm summarizing patient care strategies. 4 tables. 93 references. •

Viral Gastroenteritis Source: in Evans, A.S. and Kaslow, R.A., eds. Viral Infections of Humans: Epidemiology and Control. 4th ed. New York, NY: Plenum Medical Book Company. 1997. p. 285-343. Contact: Available from Plenum Publishing Corporation. 233 Spring Street, New York, NY 10013. (800) 221-9369. Fax (212) 647-1898. E-mail: [email protected]. PRICE: $59.50. ISBN: 0306448556 (hardback); 0306448564 (paperback). Summary: This lengthy chapter on viral gastroenteritis is from a textbook on the epidemiology and control of viral infections in humans. Despite the great importance of this problem, research studies have failed to reveal an etiologic agent (cause) for the majority of diarrheal illnesses. However, the discovery of the Norwalk virus (1972) and the rotavirus (1973) provided additional information about viral gastroenteritis. This chapter deals primarily with the rotaviruses and the Norwalk group of viruses. The Norwalk virus group has been associated with gastroenteritis outbreaks occurring in school, community, and family settings, and affecting school-aged children, adults, family contacts, and some preschool-aged children. The 70-nm rotaviruses are associated with 35-52 percent of acute diarrheal diseases of infants and young children requiring hospitalization in developed countries. Other viral agents that play a role in these diarrheal syndromes are discussed at the end of the chapter. The author covers historical background, the methodology involved in epidemiologic analysis, sources of mortality and morbidity data, laboratory methods, epidemic behavior, geographic distribution, temporal distribution, socioeconomic status, incidence and prevalence data, pathogenesis and immunity, patterns of host response, and control and prevention considerations. 10 figures. 7 tables. 656 references. (AA-M).

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Clinical Practice Guideline: The Management of Acute Gastroenteritis in Young Children Source: in American Academy of Pediatric. Pediatric Clinical Practice Guidelines and Policies: A Compendium of Evidence-based Research for Pediatric Practice. Elk Grove Village, IL: American Academy of Pediatrics. 2001. p. 182-194. Contact: Available from American Academy of Pediatrics. P.O. Box 927, 141 Northwest Point Boulevard, Elk Grove Village, IL 60009-0927. (800) 433-9016. PRICE: $47.95 (members) plus $6.25 shipping and handling; $52.95 for nonmembers; plus $8.95 shipping and handling. ISBN: 1581100701. Summary: This practice parameter formulates recommendations for health care providers about the management of acute diarrhea in children ages 1 month to 5 years. It was developed through a comprehensive search and analysis of the medical literature. Three specific management issues were considered: methods of rehydration, refeeding

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after rehydration, and the use of antidiarrheal agents. Main outcomes considered were success or failure of rehydration, resolution of diarrhea, and adverse effects from various treatment options. Oral rehydration was found to be as effective as intravenous therapy in rehydrating children with mild to moderate dehydration and is the therapy of first choice in these patients. Refeeding was supported by enough comparable studies to permit valid analysis. Early refeeding with milk or food after rehydration does not prolong diarrhea; there is evidence that it may reduce the duration of diarrhea by approximately half a day and is recommended to restore nutritional balance as soon as possible. Data on antidiarrheal agents were not sufficient to demonstrate efficacy; therefore, the routine use of antidiarrheal agents is not recommended, because many of these agents have potentially serious adverse effects in infants and young children. 1 figure. 3 tables. 93 references. •

Technical Report Practice Parameter: Acute Gastroenteritis Source: in American Academy of Pediatrics. Clinical Practice Guidelines of the American Academy of Pediatrics: A Compendium [Compilation] of Evidence-Based Research for Pediatric Practice. Elk Grove Village, IL: American Academy of Pediatrics. 1999. p. 147-197. Contact: Available from American Academy of Pediatrics. P.O. Box 747, Elk Grove Village, IL 60009-0747. (800) 433-9016 or (947) 228-5005. Fax (847) 228-1281. PRICE: $39.95 for members; $44.95 for nonmembers. ISBN: 1581100264. Summary: This technical report was prepared to support the Clinical Practice Guideline from the American Academy of Pediatrics that offers recommendations for the management of acute diarrhea in children ages 1 month to 5 years. Three specific management issues are considered: methods of rehydration, refeeding after rehydration, and the use of antidiarrheal agents. Main outcomes considered by the subcommittee that created the Guideline were success or failure of rehydration, resolution of diarrhea, and adverse effects from various treatment options. The technical report details the process followed in the development of the Guideline, and presents the evidence used to formulate the final recommendations. The literature search identified 230 articles that could potentially be included in the parameter. Of these, 88 compared (ORT) with (IV) therapy for dehydration, 46 compared different refeeding strategies, and 76 reported the effects of symptomatic drug therapy. Tables in this report summarize the data from these articles. Oral rehydration was found to be as effective as intravenous therapy in rehydrating children with mild to moderate dehydration and is the therapy of first choice in these patients. Early refeeding with milk or food after rehydration does not prolong diarrhea; there is evidence that it may reduce the duration of diarrhea by approximately half a day and is recommended to restore nutritional balance as soon as possible. Data on antidiarrheal agents were not sufficient to demonstrate efficacy; therefore, the routine use of antidiarrheal agents is not recommended, because many of these agents have potentially serious adverse effects in infants and young children. 1 appendix. 5 figures. 13 tables. 188 references.

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CHAPTER

6.

PERIODICALS AND GASTROENTERITIS

NEWS

ON

Overview In this chapter, we suggest a number of news sources and present various periodicals that cover gastroenteritis.

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

Antiemetics often given to children with gastroenteritis, side effects rare Source: Reuters Medical News Date: May 26, 2003

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•

Norwalk-like virus responsible for gastroenteritis outbreak in Afghanistan Source: Reuters Medical News Date: June 07, 2002

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Ondansetron improves outcomes of gastroenteritis-related vomiting in ER setting Source: Reuters Industry Breifing Date: April 26, 2002

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Gastroenteritis is associated with elevated serum amylase levels Source: Reuters Medical News Date: April 01, 2002

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CDC establishes computer network to track gastroenteritis Source: Reuters Medical News Date: July 20, 2000

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Interactive fountain linked to gastroenteritis outbreak Source: Reuters Health eLine Date: July 05, 2000

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Bacterial gastroenteritis linked to increased risk of irritable bowel syndrome Source: Reuters Medical News Date: February 26, 1999

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L. Monocytogenes In Milk Causes Outbreak Of Gastroenteritis And Fever Source: Reuters Medical News Date: January 10, 1997

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Gastroenteritis Kills 234 In Eastern India Source: Reuters Medical News Date: June 27, 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

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Market Wire’s home page at http://www.marketwire.com/mw/home, type “gastroenteritis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “gastroenteritis” (or synonyms). If you know the name of a company that is relevant to gastroenteritis, 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 “gastroenteritis” (or synonyms).

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

Dietary Factors in Gastrointestinal Diseases Source: Networking News. 20(4): 1, 5, 10. Summer 1999. Contact: Available from Nutrition Education for the Public. ADA/DPG 52, Bill Evers, 2971 Soldiers Home Road, West Lafayette, IN 47906-1660. Summary: This newsletter article reviews the role of dietary factors in gastrointestinal diseases. Many factors have been implicated to produce worsening of symptoms of functional gastrointestinal disorders (FGID), such as irritable bowel syndrome (IBS), including stress and diet. The author discusses several specific diseases that are associated with adverse reactions to food. The common complaints that are associated with reactions to food are: bloating, heartburn, dyspepsia, excessive gas, diarrhea, and constipation. Some of these diseases (gastroesophageal reflux disease, celiac disease, food allergies, and lactose intolerance) are associated with specific dietary therapies that improve symptoms; each is summarized briefly. The author also discusses a rare syndrome, called eosinophilic gastroenteritis, which is treated with prednisone therapy. All of these diseases have characteristics that differentiate them from functional GI

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disorders (those without a clear underlying pathology). The author notes that a symptoms diary collected over 2 to 3 weeks can help determine the relationship of the symptoms to foods. Many individuals with FGID believe that specific foods are responsible for their symptoms, yet no clear resolution of symptoms occurs when the offending foods are eliminated. An elimination diet should be performed with the help of a health professional, since unmonitored elimination diets can produce malnutrition. 8 references.

Academic Periodicals covering Gastroenteritis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to gastroenteritis. In addition to these sources, you can search for articles covering gastroenteritis 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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APPENDICES

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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

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•

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

•

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “gastroenteritis” (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 92097 149 35 63 316 92660

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

13

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

14

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

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

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

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

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

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

•

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

18 Adapted 19

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

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

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

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Guides on gastroenteritis Gastroenteritis http://www.nlm.nih.gov/medlineplus/gastroenteritis.html

•

Other guides Food Contamination and Poisoning http://www.nlm.nih.gov/medlineplus/foodcontaminationandpoisoning.html Nausea and Vomiting http://www.nlm.nih.gov/medlineplus/nauseaandvomiting.html Rotavirus Infections http://www.nlm.nih.gov/medlineplus/rotavirusinfections.html Viral Infections http://www.nlm.nih.gov/medlineplus/viralinfections.html

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

General/Overviews Gastroenteritis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00085 Viral Gastroenteritis Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dvrd/revb/gastro/faq.htm

•

Diagnosis/Symptoms Abdominal Pain, Short-Term Source: American Academy of Family Physicians http://familydoctor.org/527.xml Diarrhea Source: American Academy of Family Physicians http://familydoctor.org/534.xml Nausea and Vomiting Source: American Academy of Family Physicians http://familydoctor.org/529.xml Nausea and Vomiting in Infants and Children Source: American Academy of Family Physicians http://familydoctor.org/530.xml Stool Tests Source: Nemours Foundation http://kidshealth.org/parent/general/sick/labtest8.html

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•

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Treatment Gastroenteritis: First Aid Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=FA00030

•

Specific Conditions/Aspects Cruising with Confidence Source: Food and Drug Administration http://www.fda.gov/fdac/features/2003/303_virus.html Foodborne Illness Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/foodborneinfections_g.htm Norovirus: Food Handlers Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirus-foodhandlers.htm Norovirus: Q&A Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirus-qa.htm

•

Children Gastrointestinal Infections and Diarrhea Source: Nemours Foundation http://kidshealth.org/parent/medical/digestive/gastrointestinal.html Rotavirus Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/rotavirus.html Vomiting Source: Nemours Foundation http://kidshealth.org/parent/firstaid_safe/emergencies/vomit.html

•

From the National Institutes of Health Viral Gastroenteritis Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/viralgastroenteritis/index.htm

•

Organizations Centers for Disease Control and Prevention http://www.cdc.gov/ National Center for Infectious Diseases http://www.cdc.gov/ncidod/index.htm National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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Prevention/Screening Clean Your Hands: A Simple Way to Prevent Infection Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00407 Cruise Ships and Gastrointestinal Illness: How to Keep the Bug at Bay Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00498

•

Research Researchers Identify Cause of Diarrheal Illness in Nursing Homes Source: National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/jan2002/niaid-08.htm

•

Teenagers Dangers of Dehydration Source: Nemours Foundation http://kidshealth.org/teen/safety/first_aid/dehydration.html Gastrointestinal Infections and Diarrhea Source: Nemours Foundation http://kidshealth.org/teen/infections/intestinal/diarrhea.html

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

Vibrio vulnificus Fact Sheet for Health Care Providers Source: Cedar Grove, NJ: American Liver Foundation. 2001. [2 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) 4HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling.

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Summary: Every year, millions of Americans consume raw molluscan shellfish, especially oysters and clams. For some people, eating these shellfish raw or undercooked can cause serious illness or death from Vibrio vulnificus. V. vulnificus is a gram-negative bacterium and is considered the most lethal of the vibrios bacteria inhabiting brackish and salt water. This bacterium is not the result of bacteriological or chemical pollution of marine waters, but occurs naturally in warm, coast areas. This fact sheet provides health care workers with basic information about V. vulnificus. Topics include persons at high risk, how infection occurs, the resulting illness (primary septicemia, gastroenteritis, wound infection), diagnostic considerations, treatment (notably prompt antimicrobial therapy), the long term sequelae of V. vulnificus infection, how to reduce the risk of infection, and prevention recommendations. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org). •

CMV: What You Need to Know Contact: Research and Education Group, Community Program for Clinical Research on AIDS, 2701 NW Vaughn Ste 840, Portland, OR, 97210, (503) 229-8428, http://www.reg.org. Summary: This brochure discusses cytomegalovirus (CMV), pointing out that it is one of the most common opportunistic infections in people with AIDS. It summarizes how the infection is contracted, its symptoms, treatment approaches, and methods of prevention. A final section presents background information on the Research & Education Group, producers of the brochure, which is offering participation in a clinical trial comparing oral ganciclovir to placebo for the prevention of CMV retinitis and gastroenteritis in qualifying HIV- positive persons.

•

Look After Your Insides Source: London, England: British Digestive Foundation. 1993. 4 p. Contact: Available from British Digestive Foundation. 7 Chandos Street, London W1A 2LN England. PRICE: Single copy free. Summary: This health education brochure provides basic information about digestive tract diseases. Topics include the importance of regular, healthy living in the prevention of digestive tract problems; the role of eating well; how to improve one's diet; avoiding food poisoning and gastroenteritis; food problems; traveler's diarrhea; the role of alcohol consumption and recommended amounts; gastrointestinal problems caused or exacerbated by smoking; reducing stress; exercise; problems arising from certain prescribed drugs; and suggestions for gastrointestinal problems during pregnancy. In addition, the brochure outlines recommendations for determining when to consult with a health care provider. The brochure concludes with a brief description of the activities of the British Digestive Foundation.

•

Escherichia Coli O157:H7 Infection Source: American Family Physician. 56(3): 859-861. September 1, 1997. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This three page fact sheet reviews basic information about Escherichia coli O157:H7 infection and how to prevent it. E. coli is the name of a strain of bacteria that causes severe gastroenteritis (cramps and diarrhea). E. coli is one of the leading causes

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of bloody diarrhea. The symptoms are worse in children and older people, and especially in people who have another illness. Written in a question and answer format, the fact sheet covers how E. coli infection is transmitted, the symptoms of E. coli infection, complications arising from E. coli infection, diagnostic strategies for establishing E. coli infection, treatment options, and ways to prevent infection with E. coli. The most common way to get this infection is by eating rare (undercooked) hamburgers. The germ can also be passed from person to person in day care centers and nursing homes. The most common complication of E. coli infection is hemolytic uremic syndrome (HUS), which consists of hemolytic anemia (low red blood cell count), thrombocytopenia (low platelet count), and renal (kidney) failure. A stool culture is required to confirm E. coli infection. There is no special treatment for E. coli infection, except hydration (drinking a lot of water) and watching for complications. The fact sheet lists rules to follow to prevent contracting foodborne infections such as E. coli. These rules cover handwashing techniques, cooking meat thoroughly, defrosting meats safely, and handling leftovers properly. The fact sheet is also available online. 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 “gastroenteritis” (or synonyms). The following was recently posted: •

Evidence based clinical practice guideline for children with acute gastroenteritis (AGE) Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1999 November (revised 2001 Apr); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3117&nbr=2343&a mp;string=gastroenteritis 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 gastroenteritis. 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

Patient Resources

•

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

•

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

•

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

•

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

•

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

•

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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to gastroenteritis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with gastroenteritis. 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 gastroenteritis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “gastroenteritis” (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

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your search to “Organizations” and “gastroenteritis”. 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 “gastroenteritis” (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 “gastroenteritis” (or a synonym) into the search box, and click “Submit Query.”

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

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

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

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

21

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

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

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

22

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

Finding Medical Libraries 115 •

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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•

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

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

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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/

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

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

•

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

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

•

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 117 •

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/

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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

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

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

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

•

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

119

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

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

•

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

•

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

•

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

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GASTROENTERITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Cramps: Abdominal pain due to spasmodic contractions of the bowel. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [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] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] 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] 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] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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,

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nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescent Nutrition: Nutrition of children aged 13-18 years. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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

Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU]

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Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amylase: An enzyme that helps the body digest starches. [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] Anal Fissure: A small tear in the anus that may cause itching, pain, or bleeding. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans.

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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] Anionic: Pertaining to or containing an anion. [EU] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Anthropogenic: Of human origin or influence. [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 lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Monoclonal: Antibodies produced by clones of cells such as those isolated after hybridization of activated B lymphocytes with neoplastic cells. These hybrids are often referred to as hybridomas. [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] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU]

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Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the

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enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrovirus: A genus of small, circular RNA viruses in the family Astroviridae. They cause gastroenteritis and are found in the stools of several vertebrates including humans. Transmission is by the fecal-oral route. There are at least seven human serotypes and the type species is human astrovirus 1. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] 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] Avian: A plasmodial infection in birds. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills,

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tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bacterial Translocation: The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH]

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Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [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] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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 Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose.

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[NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [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] Borates: Inorganic or organic salts and esters of boric acid. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile.

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Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calicivirus: A genus in the family Caliciviridae containing many species including feline calicivirus , vesicular exanthema of swine virus, and San Miguel sea lion viruses. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [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] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as

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metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholelithiasis: Presence or formation of gallstones. [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]

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Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] 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] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH]

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Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] 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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [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] Concentric: Having a common center of curvature or symmetry. [NIH]

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Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consumption: Pulmonary tuberculosis. [NIH] Contact Inhibition: Arrest of cell locomotion or cell division when two cells come into contact. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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]

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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronavirus: A genus of the family Coronaviridae which causes respiratory or gastrointestinal disease in a variety of vertebrates. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] 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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals

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in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] 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] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are

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the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]

Dyspepsia: Impaired digestion, especially after eating. [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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital

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or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work.

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Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [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] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [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] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH]

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Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [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] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling

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reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Feline Infectious Peritonitis: Common coronavirus infection of cats caused by the feline infectious peritonitis virus. The disease is characterized by a long incubation period, fever, depression, loss of appetite, wasting, and progressive abdominal enlargement. Infection of cells of the monocyte-macrophage lineage appears to be essential in FIP pathogenesis. [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] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filarioidea: A superfamily of nematodes of the suborder Spirurina. Its organisms possess a filiform body and a mouth surrounded by papillae. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances

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that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens ingested in food. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fucose: Deoxysugar. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] 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] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU]

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Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic 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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids

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(steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [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 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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanine: One of the four DNA bases. [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] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Handwashing: The act of cleansing the hands with water or other liquid, with or without the inclusion of soap or other detergent, for the purpose of removing soil or microorganisms. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody

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response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helminthiasis: Infestation with parasitic worms of the helminth class. [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] 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] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH]

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Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the opening. [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] Histology: The study of tissues and cells under a microscope. [NIH] Hog Cholera: An acute, highly contagious disease affecting swine of all ages and caused by the hog cholera virus. It has a sudden onset with high morbidity and mortality. [NIH] Hog Cholera Virus: A species of the Pestivirus genus causing exceedingly contagious and fatal hemorrhagic disease of swine. [NIH] Homeopathic remedies: Small doses of medicines, herbs, or both that are believed to stimulate the immune system. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin

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help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] 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] 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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH]

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Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH]

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In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] 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] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Information Centers: Facilities for collecting and organizing information. They may be specialized by subject field, type of source material, persons served, location, or type of services. [NIH] Information Systems: Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. [NIH] Infuse: To pour (a liquid) into something. [EU] Ingestion: Taking into the body by mouth [NIH]

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Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH]

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Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestinal Obstruction: Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anus. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intussusception: A rare disorder. A part of the intestines folds into another part of the intestines, causing blockage. Most common in infants. Can be treated with an operation. [NIH]

Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt

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solution and the blood serum. [EU] Ivermectin: A mixture of ivermectin component B1a (RN 71827-03-7) and B1b (RN 70209-813), which is a semisynthetic product from Streptomyces avermitilis. A potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasite infestations in animals. The compound has activity against internal and external parasites and has been found effective against arthropods, insects, nematodes, filarioidea, platyhelminths, and protozoa. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal

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tract and the immune system. [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] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [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] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries

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cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH]

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Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesenteric Lymphadenitis: Inflammation of the mesenteric lymph nodes. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the

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abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Hypersensitivity: Allergic reaction to milk (usually cow's milk) or milk products. In infants the hypersensitivity is manifested by colic, vomiting, diarrhea, rhinitis, wheezing, etc. Milk hypersensitivity should be differentiated from lactose intolerance, an intolerance to milk as a result of congenital deficiency of lactase. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other

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procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mung bean: A type of bean grown in warm climates. It is usually used for its seed and for bean sprouts. Mung bean may have anticancer effects. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense

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pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [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] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

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Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutralization Tests: Titration of an antiserum by testing a series of dilutions of virus or immune serum to a given end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50). [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nordihydroguaiaretic Acid: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Octamer: Eight molecules of histone. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU]

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Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] 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] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor

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molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [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] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a

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single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroral: Performed through or administered through the mouth. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer

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phenotype, characteristic of yeasts. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Diseases: Diseases of plants. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH]

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Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [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]

Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poison Control Centers: Facilities which provide information concerning poisons and treatment of poisoning in emergencies. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA 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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH]

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Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Proctitis: Inflammation of the rectum. [EU] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Prone: Having the front portion of the body downwards. [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]

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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] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] 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] Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

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Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH]

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Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Rehydration Solutions: Fluids restored to the body in order to maintain normal waterelectrolyte balance. [NIH] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH]

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Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rotavirus Infections: Infection with any of the rotaviruses. Specific infections include human infantile diarrhea, neonatal calf diarrhea, and epidemic diarrhea of infant mice. [NIH] Rotavirus Vaccines: Vaccines or candidate vaccines used to prevent infection with rotavirus. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Salmonella Infections: Infections with bacteria of the genus Salmonella. [NIH] Salmonellosis: Infection by salmonellae. [NIH] Sanitary: Relating or belonging to health and hygiene; conductive to the restoration or maintenance of health. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH]

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Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sendai: A virus that causes an important and widespread infection of laboratory mice; it belongs to the parainfluenza group of mixoviruses. The virus is widely used in cell fusion studies. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serial Passage: Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in virulence studies and the development of vaccines. [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] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the

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broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shigellosis: Infection with the bacterium Shigella. Usually causes a high fever, acute diarrhea, and dehydration. [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]

Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

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

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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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sphincters: Any annular muscle closing an orifice. [NIH] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between

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the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH]

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Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Tetravalent: Pertaining to a group of 4 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH]

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Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH]

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Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Trichuriasis: Infection with nematodes of the genus Trichuris, formerly called Trichocephalus. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of

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urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vesicular Exanthema of Swine: A calicivirus infection of swine characterized by hydropic degeneration of the oral and cutaneous epithelia. [NIH] Vesicular Exanthema of Swine Virus: The type species of the genus Calicivirus, an RNA virus infecting pigs. The resulting infection is an acute febrile disease which is clinically indistinguishable from foot and mouth disease. Transmission is by contaminated food. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH]

Dictionary 179

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] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Proteins: Proteins found in any species of virus. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] 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] Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [NIH] Vomitus: 1. Vomiting. 2. Matter vomited. [EU] Water Intoxication: A condition resulting from the excessive retention of water with sodium depletion. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

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X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

181

INDEX A Abdominal, 70, 84, 85, 86, 87, 106, 121, 132, 136, 142, 143, 155, 156, 162, 163, 177 Abdominal Cramps, 84, 121 Abdominal Pain, 84, 85, 86, 106, 121, 143, 155, 163, 177 Abortion, 79, 121, 179 Abscess, 70, 121 Acetic Acids, 78, 121 Acetylcholine, 121, 154, 160 Acidity, 11, 121 Acute Disease, 30, 121 Acute renal, 121, 146 Adaptation, 9, 70, 121 Adenosine, 121, 130, 164 Adenovirus, 15, 47, 49, 121 Adipocytes, 121, 153 Adjustment, 72, 121 Adjuvant, 16, 31, 121 Adolescent Nutrition, 86, 122 Adrenal Cortex, 122, 135, 166 Adrenergic, 122, 125, 138, 154 Adverse Effect, 90, 91, 122, 132, 172 Aerosol, 9, 122 Afferent, 122, 153 Affinity, 36, 122, 132, 172 Agar, 66, 122, 164 Agarose, 69, 122 Alertness, 122, 129 Alfalfa, 79, 122 Algorithms, 86, 122, 128 Alimentary, 122, 162, 163 Alkaline, 10, 122, 130 Alkaloid, 122, 127 Alleles, 41, 122 Allergen, 33, 122 Allergic Rhinitis, 71, 123, 146 Alternative medicine, 94, 123 Ameliorating, 18, 24, 123 Amenorrhea, 123, 124 Amino Acid Sequence, 123, 124 Amplification, 5, 75, 123 Ampulla, 123, 139 Amylase, 94, 123 Anaerobic, 123, 170 Anaesthesia, 57, 123, 150 Anal, 84, 85, 123, 142 Anal Fissure, 84, 85, 123

Analog, 18, 123, 143 Analogous, 123, 138, 176 Analytes, 123, 174 Anatomical, 123, 126, 129, 149, 171 Anemia, 89, 110, 123, 146, 155 Angioplasty, 33, 123 Animal model, 7, 9, 10, 21, 22, 36, 123 Anionic, 38, 124 Annealing, 124, 165 Anomalies, 69, 124 Anorectal, 86, 124 Anorexia, 85, 86, 124, 143 Anorexia Nervosa, 85, 86, 124 Antagonism, 124, 130, 132 Anthrax, 9, 124 Anthropogenic, 15, 124 Antibacterial, 124, 137, 173 Antibiotic, 8, 9, 25, 38, 53, 56, 70, 78, 124, 129, 173 Antibodies, 5, 10, 12, 17, 20, 37, 42, 43, 44, 47, 68, 77, 80, 124, 125, 141, 145, 149, 155, 158, 164 Antibodies, Monoclonal, 68, 124 Anticoagulant, 124, 167 Antiemetic, 4, 12, 124, 125 Antigen, 13, 32, 46, 68, 75, 76, 79, 122, 124, 125, 133, 136, 141, 147, 148, 149, 150, 156, 174 Antigen-presenting cell, 125, 136 Anti-inflammatory, 7, 12, 36, 125, 136, 145, 166 Antimicrobial, 6, 32, 38, 78, 89, 109, 125 Antioxidant, 71, 125, 160 Antipsychotic, 125, 132, 159 Antiserum, 68, 125, 160 Antiviral, 19, 27, 28, 60, 125, 151 Anus, 123, 124, 125, 126, 129, 133, 142, 152, 165, 169 Apoptosis, 14, 125, 130 Appendicitis, 19, 85, 86, 87, 125 Approximate, 18, 125 Aqueous, 125, 127, 135 Arachidonate 15-Lipoxygenase, 125, 154 Arachidonate Lipoxygenases, 125, 154 Arachidonic Acid, 71, 125, 126, 153, 160, 167 Archaea, 126, 157 Arginine, 126, 160, 177

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Aromatic, 9, 126, 132 Arterial, 126, 134, 148, 167 Arteries, 126, 128, 134, 157, 167, 175 Artery, 123, 126, 128, 135, 139, 167, 178 Assay, 18, 25, 31, 48, 50, 126, 149, 177 Astrovirus, 4, 45, 46, 47, 55, 68, 126 Asymptomatic, 89, 126 Atopic, 13, 126 Atresia, 70, 126 Atrial, 126, 134, 177 Atrioventricular, 126, 134 Atrium, 126, 134, 177, 178 Atrophy, 126, 159 Atypical, 126, 132 Autoimmune disease, 74, 126, 158 Autonomic, 12, 121, 125, 126, 163 Avian, 15, 71, 72, 126 B Bacillus, 9, 124, 126, 174 Bacteremia, 49, 126, 170 Bacterial Physiology, 121, 127 Bacterial toxin, 80, 127 Bacterial Translocation, 69, 70, 127 Bacteriophage, 127, 164, 170, 176, 179 Bacterium, 10, 18, 21, 46, 109, 127, 146, 171, 172, 177 Base, 127, 136, 143, 153, 175, 177 Benign, 51, 85, 86, 127, 146, 159, 168 Berberine, 27, 127 Bilateral, 127, 170 Bile, 25, 127, 143, 144, 148, 149, 153, 154, 173 Bile Acids, 127, 144, 173 Bile Acids and Salts, 127 Bile duct, 127, 143, 149 Bile Pigments, 127, 153 Biliary, 88, 127, 130 Bilirubin, 127, 143, 148 Bioassay, 128 Bioavailability, 30, 128 Biochemical, 12, 19, 25, 27, 28, 30, 35, 36, 40, 122, 128, 142, 171 Biological Assay, 10, 128 Biological response modifier, 128, 151 Biomolecular, 128, 174 Biophysics, 32, 128 Biotechnology, 45, 50, 94, 101, 128 Bioterrorism, 10, 29, 34, 41, 128 Bladder, 84, 128, 150, 158, 177, 178 Bloating, 95, 128, 150, 155 Blood Cell Count, 110, 128, 146 Blood Coagulation, 128, 130, 175

Blood Platelets, 128, 171, 175 Blood pressure, 128, 148, 157, 167, 173 Blood urea, 4, 128 Blood vessel, 128, 130, 134, 139, 144, 146, 155, 156, 157, 172, 173, 175, 178 Blood Volume, 4, 128 Blot, 50, 128 Body Fluids, 129, 173 Body Regions, 129, 132 Bone Marrow, 30, 33, 129, 144, 149, 155 Borates, 61, 129 Boron, 61, 129 Boron Neutron Capture Therapy, 129 Bowel Movement, 85, 129, 136, 174 Brachytherapy, 129, 152, 168, 180 Bradykinin, 129, 160 Branch, 117, 129, 138, 155, 162, 167, 173 Breakdown, 128, 129, 136, 143 Broad-spectrum, 9, 129 Bronchi, 129 Bronchial, 60, 71, 129, 147 Bronchitis, 60, 62, 129 Buccal, 129, 154 Bulimia, 85, 129 C Caffeine, 86, 129, 168 Calcium, 14, 25, 31, 37, 130, 133, 172 Calculi, 130, 145 Calicivirus, 4, 22, 27, 41, 42, 47, 48, 49, 130, 178 Caloric intake, 5, 130 Capsid, 16, 22, 26, 35, 37, 40, 41, 130, 179 Carbohydrate, 37, 130, 145, 165, 171 Carcinoembryonic Antigen, 28, 130 Carcinogenesis, 130, 131 Carcinogenic, 130, 151, 166, 173 Cardiac, 129, 130, 134, 139, 143, 158, 170, 173 Cardiovascular, 130, 153, 171 Case report, 47, 52, 130, 142 Caspase, 14, 130 Catecholamines, 13, 130, 137 Catheterization, 123, 130 Causal, 12, 130, 171 Celiac Disease, 75, 80, 84, 85, 86, 87, 95, 130 Cell Adhesion, 28, 130 Cell Death, 125, 130 Cell Differentiation, 131, 172 Cell Division, 127, 131, 134, 156, 157, 164, 166 Cell Fusion, 131, 171

Index 183

Cell membrane, 28, 131, 136, 138, 152, 156, 164 Cell motility, 131, 147 Cell proliferation, 75, 131, 151, 172 Cell Size, 131, 142 Cellulose, 131, 164 Central Nervous System, 121, 129, 131, 132, 146, 153, 154, 158, 161, 171 Central Nervous System Infections, 131, 146 Cerebrospinal, 57, 131 Cerebrospinal fluid, 57, 131 Cervix, 121, 131 Chemopreventive, 27, 131 Chemotaxis, 18, 131 Chemotherapeutic agent, 30, 131 Chemotherapy, 12, 27, 78, 131 Chimeras, 61, 131 Chlorophyll, 131, 140 Cholelithiasis, 84, 131 Cholera, 9, 11, 70, 131, 172, 179 Cholesterol, 28, 85, 86, 127, 132, 143, 148, 154, 173 Chorioretinitis, 132, 170 Choroid, 132, 170 Chromatin, 125, 132 Chromosomal, 123, 132, 164 Chromosome, 132, 145, 153, 176 Chronic, 15, 24, 26, 28, 33, 70, 80, 132, 141, 150, 167, 174, 175, 177 Chymotrypsin, 30, 132 CIS, 24, 26, 132 Clinical Medicine, 32, 132, 166 Clinical trial, 6, 7, 23, 101, 109, 132, 167, 168 Cloning, 9, 27, 41, 128, 132, 151 Clozapine, 54, 132 Cofactor, 28, 132, 167, 175 Colic, 84, 85, 132, 157 Colitis, 33, 36, 75, 80, 84, 85, 86, 132 Collagen, 123, 132, 164 Colon, 21, 36, 71, 86, 130, 132, 133, 138, 149, 150, 153, 177 Colorectal, 85, 133 Colorectal Cancer, 85, 133 Colostrum, 74, 77, 80, 133 Commensal, 10, 133 Complement, 133, 144, 153 Complementary and alternative medicine, 27, 133 Complementation, 20, 133 Computational Biology, 101, 133

Concentric, 40, 133 Conception, 121, 134, 142 Concomitant, 13, 134 Conjunctiva, 134, 150 Conjunctivitis, 71, 134, 146 Connective Tissue, 129, 132, 134, 142, 155, 156, 170, 175 Constipation, 84, 85, 86, 87, 95, 125, 134, 163 Constitutional, 134, 158, 170 Consumption, 11, 17, 49, 109, 134, 136, 143, 169 Contact Inhibition, 69, 134 Contamination, 6, 15, 44, 69, 106, 134, 147, 170 Continuum, 17, 134 Contraindications, ii, 6, 84, 134 Convulsion, 56, 57, 128, 134 Coordination, 134, 158 Cor, 12, 134 Coronary, 33, 134, 135, 157 Coronary Thrombosis, 135, 157 Coronavirus, 26, 28, 61, 76, 78, 79, 135, 142 Corpus, 135, 166 Corpus Luteum, 135, 166 Cortex, 135, 141, 161 Corticosteroids, 74, 135, 144, 166 Cortisol, 13, 135 Cortisone, 135, 136, 166 Cranial, 135, 146, 161, 163 Craniocerebral Trauma, 135, 146 Cryptosporidiosis, 44, 135 Crystallization, 9, 135 Curative, 61, 69, 70, 135 Cutaneous, 124, 135, 152, 154, 178 Cyclic, 12, 130, 135, 145, 160 Cytokine, 13, 17, 21, 135 Cytomegalovirus, 30, 33, 35, 109, 135, 143 Cytomegalovirus Infections, 135, 143 Cytoplasm, 37, 125, 131, 135, 140, 145, 170 Cytotoxic, 14, 50, 135, 149, 168, 172 D Day Care, 110, 135 Defense Mechanisms, 19, 70, 135 Degenerative, 136, 147 Dehydration, 3, 4, 54, 79, 84, 89, 90, 91, 108, 131, 136, 172 Deletion, 38, 125, 136 Delivery of Health Care, 136, 146 Denaturation, 136, 165 Dendrites, 136, 159 Dendritic, 23, 136, 173

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Dendritic cell, 23, 136 Density, 15, 76, 136, 142, 154, 161 Depolarization, 136, 172 Dermatitis, 13, 136 Developed Countries, 18, 90, 136 Developing Countries, 11, 21, 23, 39, 41, 136 Developmental Biology, 8, 136 Dexamethasone, 12, 136 Diagnostic procedure, 67, 95, 136 Diaphragm, 136, 147, 165 Diarrhoea, 62, 136, 143 Digestion, 122, 127, 129, 136, 138, 150, 152, 154, 163, 173 Digestive system, 136, 144 Digestive tract, 74, 85, 109, 136, 172 Dilatation, 121, 123, 137, 178 Dilution, 137, 141, 160 Dimerization, 30, 137 Dimethyl, 71, 137, 154 Diploid, 68, 69, 133, 137, 164 Direct, iii, 13, 15, 21, 39, 43, 48, 80, 132, 137, 138, 162, 169, 175 Discrete, 72, 137 Disease Transmission, 17, 72, 137 Disease Transmission, Horizontal, 137 Disease Transmission, Vertical, 137 Disinfection, 39, 137 Dislocation, 17, 137 Dissection, 29, 40, 137 Dissociation, 122, 137 Distal, 17, 137, 144, 167 Diuresis, 129, 137 Diurnal, 13, 137 Diverticula, 137 Diverticulitis, 85, 86, 137 Diverticulum, 137 Dopamine, 125, 132, 137, 160 Drug Design, 30, 138 Drug Tolerance, 138, 176 Duodenal Ulcer, 86, 138 Duodenum, 86, 127, 132, 138, 139, 143, 162, 174 Dura mater, 138, 156, 162 Dysentery, 84, 138 Dyspepsia, 86, 95, 138, 150 E Edema, 138, 161 Effector, 8, 23, 43, 121, 133, 138 Efficacy, 12, 18, 23, 31, 35, 39, 80, 90, 91, 138 Electrolyte, 31, 89, 138, 169, 173

Electrophysiological, 32, 138 Electroporation, 14, 138 Embryo, 121, 131, 138, 150 Emergency Medicine, 85, 138 Emergency Treatment, 87, 139 Encapsulated, 40, 139 Encephalitis, 26, 29, 41, 139 Encephalitis, Viral, 139 Encephalomyelitis, 28, 139 Endarterectomy, 123, 139 Endemic, 4, 65, 131, 139, 155, 173 Endocarditis, 29, 139 Endocardium, 139 Endocrine System, 139, 159 Endogenous, 40, 137, 139, 167 Endoscope, 139 Endoscopic, 86, 139 Endothelium, 139, 160 Endothelium-derived, 139, 160 Endotoxic, 139, 154 Endotoxin, 8, 139 Energy balance, 139, 153 Enhancer, 34, 140 Enteric bacteria, 19, 140 Enteritis, 65, 84, 140 Enterocolitis, 13, 140 Enterocytes, 76, 140 Enteropeptidase, 140, 177 Enterotoxins, 18, 140 Environmental Exposure, 39, 140, 161 Environmental Health, 17, 100, 102, 140 Enzymatic, 123, 130, 133, 140, 147, 165 Eosinophil, 33, 140 Eosinophilia, 88, 140 Eosinophilic, 13, 33, 52, 53, 60, 61, 75, 80, 88, 95, 140 Eosinophilic Gastroenteritis, 13, 33, 60, 61, 75, 80, 88, 95, 140 Epidemic, 22, 26, 28, 41, 65, 90, 140, 170, 173 Epidemiological, 15, 46, 47, 57, 65, 81, 140, 142 Epidermal, 36, 140 Epidermal Growth Factor, 36, 140 Epidermal growth factor receptor, 36, 140 Epidermis, 140, 141, 168 Epigastric, 141, 162 Epithelial, 8, 10, 11, 14, 23, 24, 32, 34, 36, 69, 70, 140, 141, 145, 147, 162 Epithelial Cells, 23, 24, 36, 140, 141, 147 Epithelium, 24, 43, 139, 140, 141, 143 Epitopes, 13, 76, 141

Index 185

Erythema, 141, 178 Erythrocyte Indices, 128, 141 Erythrocyte Volume, 128, 141 Erythrocytes, 123, 128, 129, 141, 169 Esophageal, 86, 141 Esophagitis, 60, 75, 80, 86, 141 Esophagus, 86, 126, 136, 137, 141, 144, 146, 154, 163, 169, 174 Evacuation, 134, 141 Evoke, 141, 173 Excitation, 141, 142, 160 Exhaustion, 124, 141, 155 Exocrine, 141, 162 Exogenous, 139, 141, 144, 167 Extensor, 141, 167 External-beam radiation, 141, 152, 168, 180 Extracellular, 18, 134, 141, 173 Eye Infections, 121, 141 F Faecal, 136, 141 Family Planning, 101, 141 Fat, 86, 121, 126, 127, 129, 133, 134, 142, 153, 154, 158, 173 Fatal Outcome, 142, 168 Fatty acids, 142, 154, 167, 175 Fecal Incontinence, 86, 142, 150 Feces, 4, 6, 130, 134, 141, 142, 174 Feline Infectious Peritonitis, 61, 142 Fermentation, 142, 170 Fetus, 79, 121, 142, 164, 178 Fibrosis, 31, 142, 171 Filarioidea, 142, 153 Filtration, 39, 142 Fistula, 142, 143 Flatulence, 84, 86, 142 Flatus, 142, 143 Flow Cytometry, 22, 142 Fluorescence, 142, 143 Fluorescent Dyes, 142 Fold, 24, 143, 156 Food Hypersensitivity, 14, 143 Fractionation, 77, 143 Frameshift, 143, 177 Frameshift Mutation, 143, 177 Fucose, 18, 143 Fungi, 9, 141, 143, 152, 157, 180 G Gallbladder, 121, 127, 136, 143, 144 Gallstones, 84, 85, 127, 131, 143 Ganciclovir, 109, 143 Gangrenous, 143, 172

Gas, 84, 85, 86, 95, 142, 143, 148, 150, 155, 160, 174, 178 Gastric, 10, 11, 12, 51, 86, 140, 143, 144, 146, 147, 163 Gastric Juices, 143, 163 Gastric Mucosa, 143, 163 Gastritis, 84, 85, 86, 143 Gastroduodenal, 86, 143 Gastroenterology, 5, 8, 52, 85, 86, 144 Gastroesophageal Reflux, 86, 95, 144 Gastrointestinal tract, 8, 10, 18, 19, 21, 33, 36, 70, 80, 88, 127, 130, 142, 144, 153, 154, 171 Gene, 25, 27, 34, 35, 37, 38, 41, 42, 51, 121, 122, 128, 144, 151, 161, 169 Gene Expression, 27, 34, 35, 37, 38, 144 Gene Expression Profiling, 27, 144 Gene Targeting, 35, 144 Gene Therapy, 121, 144 Genetic Engineering, 128, 132, 144 Genetic testing, 144, 165 Genetics, 19, 29, 37, 144, 157 Genital, 144, 178 Genitourinary, 144, 178 Genotype, 15, 48, 144, 163 Gland, 122, 135, 144, 155, 162, 171, 173, 174 Glomerular, 144, 169 Glomerulus, 144, 159 Glucocorticoid, 136, 144, 166 Gluconeogenesis, 145 Gluten, 130, 145 Glycine, 123, 127, 145, 160, 171 Glycogen, 145 Glycoprotein, 14, 130, 145, 175 Glycosidic, 145, 161 Goblet Cells, 140, 145 Gout, 84, 86, 145 Governing Board, 145, 166 Graft, 145, 148 Gram-negative, 19, 23, 109, 127, 139, 145, 170, 179 Granulocytes, 145, 153, 172, 179 Gravis, 74, 145 Growth, 66, 69, 70, 74, 124, 125, 131, 136, 140, 145, 147, 151, 155, 159, 161, 164, 179 Guanine, 23, 145, 168 Guanylate Cyclase, 145, 160 H Haemorrhage, 121, 145 Handwashing, 110, 145 Haploid, 145, 164

186

Gastroenteritis

Haptens, 122, 145 Hay Fever, 71, 123, 146 Headache, 12, 129, 146, 150 Headache Disorders, 146 Health Care Costs, 6, 21, 146 Health Education, 109, 146 Health Expenditures, 146 Heart failure, 146, 161 Heartburn, 85, 86, 95, 146, 147, 150 Helminthiasis, 84, 131, 146 Hematocrit, 128, 141, 146 Hemoglobin, 123, 128, 141, 146 Hemolytic, 88, 110, 146 Hemorrhage, 84, 86, 135, 146, 168 Hemorrhoids, 75, 80, 84, 147 Hepatitis, 26, 28, 30, 33, 69, 84, 85, 87, 147, 179 Hepatitis A, 30, 147 Hepatocyte, 54, 147 Hepatocyte Growth Factor, 54, 147 Hepatovirus, 147 Heredity, 144, 147 Herpes, 30, 147 Herpes Zoster, 147 Heterogeneity, 56, 122, 147 Heterotrophic, 143, 147 Hiatal Hernia, 85, 86, 147 Histamine, 125, 147, 154 Histology, 86, 147 Hog Cholera, 69, 147 Hog Cholera Virus, 147 Homeopathic remedies, 85, 147 Homeostasis, 32, 147 Homogeneous, 134, 147 Homologous, 18, 41, 42, 122, 144, 147, 158, 175, 176 Homotypic, 16, 47, 147 Hormonal, 126, 128, 147 Hormone, 128, 135, 147, 151, 153, 156, 166, 172 Humoral, 13, 42, 148 Humour, 148 Hybrid, 14, 148 Hybridization, 124, 131, 148, 157 Hybridoma, 68, 148 Hydration, 4, 5, 110, 148 Hydrogen, 121, 127, 130, 136, 148, 157, 160, 161 Hydrolysis, 148, 164, 177 Hydroxyproline, 123, 132, 148 Hygienic, 17, 148 Hyperbilirubinemia, 148, 153

Hypercholesterolemia, 84, 148 Hypersensitivity, 13, 122, 140, 148, 153, 157 Hypertension, 146, 148 Hypertrophy, 134, 148, 177 Hyperuricemia, 145, 148 Hypothalamic, 12, 148 Hypothalamus, 148 I Id, 63, 106, 107, 108, 110, 116, 118, 148 Idiopathic, 80, 148 Ileal, 49, 148 Ileostomy, 149, 159 Ileum, 148, 149 Immune function, 43, 149 Immune response, 12, 16, 22, 41, 42, 75, 80, 122, 124, 125, 126, 135, 145, 149, 174, 178, 179 Immune Sera, 149 Immune system, 19, 22, 30, 36, 43, 84, 125, 147, 149, 154, 155, 158, 178, 179 Immunity, 16, 21, 22, 23, 34, 41, 42, 44, 73, 74, 77, 80, 90, 149, 176 Immunization, 4, 6, 31, 37, 42, 73, 74, 77, 80, 149 Immunoassay, 45, 149 Immunocompromised, 6, 149 Immunofluorescence, 14, 149 Immunogenic, 79, 149, 154 Immunoglobulin, 42, 46, 62, 80, 124, 149, 158 Immunologic, 14, 22, 23, 42, 70, 80, 86, 149, 168 Immunology, 8, 14, 22, 28, 29, 37, 52, 60, 62, 79, 121, 122, 143, 149 Immunosuppressive, 88, 145, 149 Immunosuppressive Agents, 88, 149 Impaction, 86, 149 Impairment, 141, 149, 152 Implant radiation, 149, 152, 168, 180 In vitro, 7, 10, 11, 13, 14, 16, 18, 28, 35, 36, 43, 128, 131, 144, 149, 150, 165, 171, 176 In vivo, 10, 14, 16, 18, 28, 38, 39, 42, 128, 131, 144, 149, 150, 175 Incompetence, 144, 150 Incontinence, 85, 150 Incubation, 142, 150 Incubation period, 142, 150 Indicative, 24, 87, 150, 162, 178 Indigestion, 84, 85, 86, 150, 153 Induction, 17, 24, 38, 125, 150 Infancy, 23, 86, 150

Index 187

Infant Mortality, 12, 150 Infarction, 135, 150, 157 Infectious Diarrhea, 6, 86, 150 Inflammatory bowel disease, 24, 36, 70, 75, 80, 85, 150 Influenza, 86, 150 Information Centers, 84, 150 Information Systems, 44, 150 Infuse, 20, 150 Ingestion, 72, 124, 150, 165 Inhalation, 122, 151, 165 Initiation, 21, 151 Initiator, 128, 151 Inlay, 151, 169 Inorganic, 129, 151, 158 Insecticides, 151, 163 Insertional, 10, 151 Insight, 27, 40, 151 Insulator, 151, 158 Insulin, 128, 151 Interferon, 22, 60, 151 Interferon-alpha, 151 Interleukin-1, 7, 151 Interleukin-2, 151 Interleukins, 149, 151 Internal Medicine, 5, 144, 151 Internal radiation, 152, 168, 180 Interstitial, 129, 152, 156, 159, 169, 180 Intestinal Flora, 70, 152 Intestinal Mucosa, 70, 80, 127, 130, 140, 152 Intestinal Obstruction, 86, 152 Intestine, 9, 10, 11, 24, 33, 70, 84, 86, 127, 129, 133, 140, 152, 153, 179 Intoxication, 152, 179 Intracellular, 14, 25, 27, 31, 32, 38, 40, 130, 150, 152, 156, 160, 172 Intracellular Membranes, 152, 156 Intramuscular, 73, 152, 162 Intravascular, 4, 152 Intravenous, 4, 89, 90, 91, 152, 162 Intrinsic, 25, 122, 152 Intussusception, 23, 31, 152 Invasive, 149, 152 Involuntary, 134, 142, 152, 158, 169, 172 Ionizing, 140, 152, 168 Ions, 121, 127, 137, 138, 148, 152 Irradiation, 39, 86, 129, 152, 180 Irritants, 138, 152 Isotonic, 5, 152 Ivermectin, 60, 153

J Jaundice, 84, 148, 153 Joint, 17, 153, 154, 175 K Karyotype, 69, 153 Kb, 26, 100, 153 L Labile, 18, 133, 153 Lactation, 133, 153 Lactose Intolerance, 85, 95, 153, 157 Large Intestine, 133, 136, 137, 140, 152, 153, 169, 172, 179 Latency, 34, 153 Latent, 30, 153 Leptin, 70, 153 Lethal, 4, 28, 54, 109, 127, 153 Lethargy, 79, 153 Leucocyte, 140, 153 Leukocytes, 128, 129, 145, 151, 153 Leukotrienes, 8, 126, 153 Library Services, 116, 154 Life cycle, 30, 34, 143, 154 Ligaments, 134, 154 Ligands, 154, 174 Lipid, 32, 37, 151, 154, 158 Lipid A, 32, 154 Lipopolysaccharide, 38, 145, 154 Lipoprotein, 145, 154, 179 Lipoxygenase, 71, 126, 153, 154, 160 Localized, 15, 36, 121, 139, 150, 154, 161, 164, 177, 178 Locomotion, 134, 154, 164 Longitudinal Studies, 42, 48, 154 Loop, 26, 149, 154 Loperamide, 54, 154 Lower Esophageal Sphincter, 144, 154 Lumen, 19, 154 Lupus, 85, 154, 175 Luxation, 137, 154 Lymph, 19, 70, 127, 139, 148, 154, 155, 156, 174 Lymph node, 19, 70, 127, 155, 156 Lymphatic, 139, 150, 154, 155, 156, 161, 173, 175 Lymphatic system, 154, 155, 173, 175 Lymphocyte, 22, 124, 155, 156 Lymphocyte Subsets, 22, 155 Lymphoid, 8, 17, 124, 135, 153, 155 Lysine, 155, 177 Lytic, 155, 171, 179 M Macrophage, 142, 151, 155

188

Gastroenteritis

Malabsorption, 84, 86, 130, 155, 172 Malabsorption syndrome, 155, 172 Malaria, 29, 84, 155 Malaria, Falciparum, 155 Malaria, Vivax, 155 Malignant, 86, 155, 159, 168, 170 Malignant tumor, 86, 155 Malnutrition, 61, 87, 96, 126, 155 Mammary, 79, 133, 155 Mastitis, 79, 155, 172 Meat, 8, 11, 110, 156 Mediate, 44, 138, 156 Mediator, 7, 12, 21, 151, 156, 172 MEDLINE, 101, 156 Medroxyprogesterone, 75, 80, 156 Medroxyprogesterone Acetate, 75, 80, 156 Meiosis, 156, 158, 175 Membrane Fusion, 28, 156 Memory, 17, 21, 124, 156 Meninges, 131, 135, 138, 156 Meningitis, 70, 156 Menstrual Cycle, 156, 166 Mental, iv, 7, 100, 102, 137, 150, 156, 167, 171, 177 Mental Health, iv, 7, 100, 102, 156, 167 Mercury, 142, 156 Mesenchymal, 140, 156 Mesenteric, 19, 70, 127, 156 Mesenteric Lymphadenitis, 19, 156 Mesentery, 156, 163 Metabolic disorder, 145, 157 Metabolite, 137, 157 Metaphase, 157, 175 Methionine, 137, 157 MI, 119, 157 Microbiology, 8, 14, 19, 28, 29, 33, 43, 53, 54, 57, 60, 61, 74, 121, 126, 157 Microorganism, 132, 157, 162, 179 Microscopy, 5, 14, 20, 24, 50, 68, 157 Migration, 17, 24, 80, 157 Milk Hypersensitivity, 13, 157 Mitosis, 125, 157 Mobilization, 14, 31, 157 Modeling, 138, 157 Modification, 32, 38, 71, 123, 144, 157 Molecular Probes, 138, 157 Monitor, 17, 130, 157, 160 Monoclonal, 40, 43, 61, 68, 76, 152, 158, 168, 180 Monoclonal antibodies, 40, 61, 68, 76, 158 Monocyte, 142, 158 Mononuclear, 158

Morphogenesis, 40, 158 Morphological, 24, 138, 158 Morphology, 8, 20, 126, 158 Motility, 18, 84, 86, 158, 171 Motion Sickness, 158 Mucins, 140, 145, 158 Mucosa, 31, 36, 49, 143, 154, 158 Mucus, 10, 138, 158, 177 Multiple sclerosis, 74, 158 Multivalent, 16, 158 Mung bean, 62, 158 Myalgia, 150, 158 Myasthenia, 74, 158 Myelin, 158 Myeloma, 148, 158 Myocardium, 157, 158 N Naive, 16, 158 Nasal Mucosa, 150, 158 Nausea, 13, 84, 86, 106, 124, 125, 143, 150, 158, 177 NCI, 1, 99, 132, 159 Necrotizing Enterocolitis, 70, 84, 159 Need, 3, 5, 9, 16, 27, 29, 34, 35, 70, 72, 83, 87, 88, 95, 109, 111, 145, 159, 176 Neonatal, 16, 60, 76, 150, 159, 170 Neoplasm, 159, 170 Neoplastic, 124, 159 Nephritis, 26, 159 Nerve, 122, 136, 156, 158, 159, 161, 166, 171, 173, 176, 178 Nervous System, 122, 131, 156, 159, 163, 168 Networks, 11, 17, 38, 159 Neural, 122, 148, 159 Neurodegenerative Diseases, 28, 159 Neuroendocrine, 12, 159 Neuroleptic, 125, 132, 159 Neuromuscular, 10, 121, 159 Neuronal, 159 Neurons, 136, 159, 175 Neuropeptides, 8, 159 Neuroretinitis, 159, 170 Neurotic, 159, 178 Neurotransmitter, 121, 123, 129, 137, 145, 147, 160, 172, 174 Neutralization, 17, 37, 76, 77, 160 Neutralization Tests, 17, 160 Neutrons, 129, 152, 160, 168 Neutrophil, 7, 160 Nitric Oxide, 24, 60, 160 Nitrogen, 4, 122, 160

Index 189

Nordihydroguaiaretic Acid, 71, 160 Nosocomial, 34, 38, 55, 160 Nuclear, 36, 160 Nucleic acid, 130, 148, 160, 168 Nucleus, 125, 132, 135, 156, 158, 160, 166, 174 O Octamer, 26, 160 Odour, 126, 160 Oedema, 61, 161 Oligosaccharides, 18, 161 Oncogene, 147, 161 Opacity, 136, 161 Operon, 25, 161, 169 Opportunistic Infections, 35, 109, 161 Optic Nerve, 159, 161, 162, 170 Organ Culture, 66, 161, 176 Organelles, 135, 161 Osteomyelitis, 47, 161 Osteoporosis, 86, 161 Outpatient, 6, 161 Overdosage, 84, 161 Ovum, 135, 154, 161, 166 Oxidation, 125, 161 Oxidative metabolism, 153, 162 P Pachymeningitis, 156, 162 Pancreas, 88, 121, 132, 136, 144, 151, 162, 177 Pancreatic, 85, 132, 144, 162 Pancreatic cancer, 85, 162 Pancreatic Juice, 132, 144, 162 Paneth Cells, 140, 162 Paralysis, 10, 162 Parasite, 153, 162, 177 Parasitic, 34, 60, 61, 62, 84, 86, 127, 135, 138, 146, 162 Parasitic Diseases, 86, 162 Parenteral, 70, 76, 162 Parenteral Nutrition, 70, 162 Pathogen, 14, 15, 19, 23, 25, 26, 28, 36, 39, 75, 150, 162 Pathogenesis, 6, 8, 12, 19, 22, 23, 24, 28, 29, 35, 38, 41, 42, 43, 76, 79, 88, 90, 142, 162 Pathologic, 125, 134, 148, 162, 167 Pathologic Processes, 125, 162 Pathophysiology, 5, 10, 88, 162 Patient Education, 108, 114, 116, 119, 162 Pepsin, 162, 163 Pepsin A, 162, 163 Peptic, 11, 163 Peptic Ulcer, 11, 163

Peptide, 123, 140, 153, 162, 163, 167, 174 Perforation, 163, 179 Pericardium, 163, 175 Periodontitis, 29, 163 Peripheral blood, 13, 151, 163 Peripheral Nervous System, 159, 160, 163, 174 Peritoneal, 88, 161, 163 Peritoneal Cavity, 161, 163 Peritoneum, 156, 163 Peritonitis, 142, 163, 179 Peroral, 22, 163 Pesticides, 86, 151, 163 Phantom, 85, 163 Pharmacokinetic, 30, 163 Pharmacologic, 163, 176 Pharynx, 144, 150, 163 Phenotype, 13, 18, 133, 163 Phospholipases, 164, 172 Phospholipids, 142, 154, 164 Phosphorus, 130, 164 Physical Examination, 3, 164 Physiologic, 152, 156, 164, 168 Physiology, 10, 31, 38, 85, 86, 138, 144, 164 Placenta, 164, 166 Plague, 9, 164 Plant Diseases, 140, 164 Plants, 9, 39, 79, 84, 122, 127, 128, 158, 164, 176, 177 Plaque, 123, 164 Plasma, 14, 124, 128, 131, 146, 158, 164 Plasma cells, 124, 158, 164 Plasmid, 51, 164, 178 Platelet Activation, 164, 172 Platelet Aggregation, 160, 164, 175 Platelet Count, 110, 165 Platelets, 160, 164, 165 Platinum, 154, 165 Platyhelminths, 153, 165 Pleural, 161, 165 Pleural cavity, 161, 165 Pneumonia, 34, 35, 134, 165 Pneumonitis, 30, 33, 165 Poison Control Centers, 84, 165 Poisoning, 70, 72, 85, 86, 106, 109, 143, 152, 156, 159, 165, 170, 171 Polymerase, 5, 30, 165, 169 Polymerase Chain Reaction, 5, 165 Polymorphic, 15, 165 Polymorphism, 16, 165 Polyposis, 86, 133, 165 Polysaccharide, 122, 124, 131, 165

190

Gastroenteritis

Posterior, 123, 132, 162, 165 Postmenopausal, 161, 165 Postoperative, 70, 166 Postsynaptic, 166, 172, 175 Potentiates, 151, 166 Potentiating, 128, 166 Potentiation, 166, 172 Practice Guidelines, 89, 90, 91, 102, 110, 166 Precancerous, 131, 166 Precursor, 126, 137, 138, 140, 166, 177 Prednisolone, 74, 166 Prednisone, 95, 166 Prevalence, 18, 28, 44, 48, 49, 55, 57, 90, 166 Proctitis, 21, 75, 80, 166 Progesterone, 75, 80, 166, 173 Prognostic factor, 166, 174 Progression, 7, 124, 166 Progressive, 131, 138, 142, 145, 159, 164, 166, 169 Projection, 136, 161, 166 Promoter, 24, 34, 166 Prone, 69, 166 Prophase, 158, 166, 175 Prophylaxis, 60, 62, 167, 178 Proportional, 167, 174 Prostaglandins, 126, 167 Protease, 20, 30, 35, 37, 40, 167 Protein Binding, 37, 167 Protein C, 31, 32, 77, 123, 127, 154, 167, 177, 179 Protein S, 27, 29, 43, 128, 167, 170 Protocol, 6, 167 Protozoa, 138, 153, 157, 167, 177 Protozoan, 131, 135, 155, 167, 177 Proximal, 17, 26, 34, 137, 167 Psoriasis, 71, 75, 80, 167 Psychoactive, 167, 179 Public Health, 4, 5, 12, 14, 23, 25, 35, 39, 44, 51, 53, 62, 102, 167 Public Policy, 101, 167 Pulmonary, 128, 134, 140, 153, 167, 178 Pulmonary hypertension, 134, 167 Pulse, 157, 167 Purines, 168, 171 Purpura, 89, 145, 168 Pyogenic, 161, 168, 171 Pyrimidines, 168, 171 R Rabies, 69, 168 Race, 153, 157, 168

Radiation, 140, 141, 142, 143, 152, 163, 168, 179, 180 Radiation therapy, 141, 143, 152, 168, 180 Radioactive, 148, 149, 152, 157, 158, 160, 168, 180 Radiolabeled, 152, 168, 180 Radiotherapy, 129, 152, 168, 180 Randomized, 12, 13, 39, 61, 138, 168 Reactive Oxygen Species, 75, 168 Receptor, 7, 13, 14, 18, 24, 27, 31, 36, 40, 61, 121, 124, 132, 138, 147, 168, 171, 172 Recombinant, 9, 25, 27, 34, 37, 40, 41, 43, 46, 77, 168, 178 Recombinant Proteins, 25, 168 Recombination, 144, 169 Rectal, 84, 169 Rectum, 75, 124, 125, 129, 133, 136, 137, 142, 143, 150, 153, 166, 169 Red blood cells, 141, 146, 169 Refer, 1, 129, 133, 143, 147, 154, 158, 159, 160, 169, 176 Reflex, 33, 169 Reflux, 85, 144, 169 Refraction, 169, 173 Regimen, 138, 169 Regulon, 39, 169 Regurgitation, 144, 146, 169 Rehydration, 4, 5, 6, 52, 54, 61, 89, 90, 91, 169 Rehydration Solutions, 4, 169 Reinfection, 23, 169 Renal failure, 89, 169 Replicon, 26, 41, 169 Repressor, 34, 161, 169 Resection, 70, 84, 169, 172 Respiration, 157, 162, 169, 170 Restoration, 4, 169, 170 Resuscitation, 138, 170 Retina, 132, 159, 161, 170 Retinitis, 30, 33, 35, 109, 170 Reversion, 170, 177 Rhinitis, 157, 170, 172 Ribonuclease, 35, 170 Ribosome, 170, 176 Rigidity, 164, 170 Rod, 126, 127, 170 Rodenticides, 163, 170 Rotavirus Infections, 23, 106, 170 Rotavirus Vaccines, 23, 31, 170 S Salivary, 135, 136, 162, 170, 174 Salivary glands, 135, 136, 170

Index 191

Salmonella, 8, 10, 15, 23, 24, 32, 38, 43, 46, 47, 49, 52, 53, 56, 62, 143, 170 Salmonella Infections, 32, 170 Salmonellosis, 8, 38, 170 Sanitary, 17, 170 Sanitation, 17, 170 Sarcoma, 31, 170 Scatter, 163, 170 Schizoid, 171, 179 Schizophrenia, 171, 179 Schizotypal Personality Disorder, 171, 179 Sclerosis, 74, 158, 171 Screening, 9, 77, 108, 132, 171 Secretion, 9, 14, 19, 25, 31, 43, 84, 140, 147, 148, 151, 153, 158, 171 Secretory, 8, 23, 31, 36, 80, 86, 171, 175 Sedative, 171, 178 Semisynthetic, 153, 171 Sendai, 74, 171 Senile, 161, 171 Sepsis, 47, 70, 127, 171 Septic, 29, 171 Septicaemia, 171, 172 Septicemia, 14, 109, 171 Sequence Analysis, 25, 171 Sequencing, 15, 20, 41, 165, 171 Serial Passage, 75, 171 Serine, 30, 132, 171, 174, 177 Serologic, 149, 171 Serotonin, 125, 132, 160, 171 Serotypes, 16, 23, 26, 126, 172 Serous, 133, 139, 172 Serum, 4, 5, 20, 57, 77, 94, 125, 133, 149, 153, 160, 163, 171, 172 Sexually Transmitted Diseases, 85, 86, 172 Shedding, 11, 31, 172 Shigellosis, 36, 172 Shock, 29, 143, 172, 177 Short Bowel Syndrome, 70, 71, 84, 86, 172 Side effect, 21, 30, 74, 84, 93, 122, 125, 148, 172, 176 Signal Transduction, 8, 14, 24, 38, 172 Skeleton, 153, 172 Skull, 135, 172, 175 Small intestine, 36, 70, 84, 86, 138, 140, 148, 149, 152, 172, 177 Smooth muscle, 33, 129, 147, 172, 174 Sneezing, 172 Sodium, 61, 88, 145, 172, 179 Soft tissue, 129, 172, 173 Somatic, 131, 148, 156, 157, 163, 173 Spasmodic, 121, 173

Specialist, 111, 173 Specificity, 35, 42, 122, 125, 173, 174 Spectrum, 89, 173 Sphincters, 142, 173 Spike, 28, 37, 40, 76, 173 Spinal cord, 131, 132, 138, 139, 156, 159, 162, 163, 169, 173 Spleen, 19, 42, 127, 135, 148, 155, 173 Sporadic, 49, 159, 173 Stasis, 12, 173 Steroid, 127, 135, 173 Stimulant, 129, 147, 173 Stimulus, 75, 141, 153, 169, 173 Stomach, 10, 84, 85, 86, 121, 128, 136, 137, 140, 141, 143, 144, 147, 148, 154, 158, 162, 163, 169, 172, 173, 179 Stool, 4, 5, 17, 39, 41, 52, 68, 106, 110, 133, 149, 150, 153, 174, 175 Strand, 26, 165, 174 Stress, 6, 10, 14, 95, 109, 135, 143, 158, 174, 178 Stupor, 153, 174 Subacute, 150, 174 Subarachnoid, 146, 174 Subclinical, 150, 174 Subcutaneous, 121, 138, 143, 161, 162, 174 Submaxillary, 140, 174 Subspecies, 15, 173, 174 Substance P, 157, 171, 174 Substrate, 25, 174 Subtilisin, 30, 174 Suction, 142, 174 Surface Plasmon Resonance, 14, 174 Survival Analysis, 10, 174 Symptomatic, 11, 17, 20, 60, 91, 174 Synapses, 173, 175 Synaptic, 160, 172, 175 Synergistic, 24, 175 Systemic, 12, 17, 19, 32, 41, 42, 74, 127, 128, 150, 152, 161, 166, 168, 171, 175, 176, 177, 180 Systemic disease, 19, 171, 175 Systemic lupus erythematosus, 74, 175 T Tachycardia, 127, 175 Tachypnea, 127, 175 Temporal, 34, 44, 65, 90, 146, 175 Tenesmus, 138, 175 Tetravalent, 23, 175 Thermal, 129, 137, 160, 165, 175 Threonine, 171, 175 Thrombin, 164, 167, 175

192

Gastroenteritis

Thrombocytopenia, 89, 110, 175 Thrombomodulin, 167, 175 Thrombosis, 167, 175 Thromboxanes, 126, 175 Thymus, 149, 155, 175 Tissue Culture, 8, 46, 69, 160, 176 Titre, 76, 176 Tolerance, 18, 176 Tonicity, 152, 176 Tooth Preparation, 121, 176 Toxic, iv, 25, 30, 127, 139, 140, 149, 176 Toxicology, 102, 176 Toxin, 139, 176 Trace element, 129, 176 Transcriptase, 5, 176 Transcutaneous, 31, 176 Transduction, 14, 38, 172, 176 Transfection, 26, 128, 138, 144, 176 Transfer Factor, 149, 176 Translation, 26, 29, 123, 176 Translational, 79, 176 Translocating, 127, 176 Translocation, 37, 127, 176 Transmitter, 121, 137, 156, 175, 176 Transplantation, 84, 149, 176 Trauma, 86, 141, 177, 179 Triad, 30, 89, 177 Trichomoniasis, 85, 177 Trichuriasis, 51, 177 Tricuspid Atresia, 134, 177 Tropism, 22, 28, 42, 177 Trypanosomiasis, 29, 177 Trypsin, 37, 40, 132, 140, 177, 180 Tunica, 139, 158, 177 TYPHI, 15, 177 Typhimurium, 8, 15, 24, 43, 47, 49, 177 Typhoid fever, 15, 23, 32, 177 Tyrosine, 130, 137, 177 U Ulcer, 138, 163, 177 Ulcerative colitis, 24, 70, 75, 80, 86, 150, 177 Unconscious, 135, 148, 177 Urea, 128, 177 Uremia, 169, 177 Ureters, 177, 178 Urethra, 177, 178 Uric, 145, 148, 168, 177 Urinary, 7, 70, 130, 144, 150, 177, 178 Urinary tract, 70, 178 Urinary tract infection, 70, 178 Urine, 128, 137, 140, 150, 177, 178

Urogenital, 79, 144, 178 Urticaria, 13, 178 Uterine Contraction, 71, 121, 178 Uterus, 121, 131, 135, 166, 178 V Vaccination, 6, 17, 21, 22, 42, 60, 80, 178 Vaccine, 4, 6, 10, 16, 19, 21, 23, 31, 34, 37, 41, 42, 68, 69, 73, 76, 78, 79, 80, 122, 167, 178 Valerian, 83, 178 Vascular, 132, 139, 146, 150, 160, 161, 164, 178 Vasodilators, 160, 178 Vector, 151, 162, 176, 178 Vegetarianism, 86, 178 Vein, 152, 160, 178 Venous, 128, 147, 161, 165, 167, 177, 178 Venous blood, 128, 165, 178 Ventricle, 126, 134, 148, 167, 177, 178 Ventricular, 134, 177, 178 Vesicular, 130, 147, 178 Vesicular Exanthema of Swine, 130, 178 Vesicular Exanthema of Swine Virus, 130, 178 Veterinary Medicine, 62, 101, 178 Vibrio, 9, 48, 50, 108, 109, 131, 179 Vibrio cholerae, 131, 179 Villous, 130, 179 Viral Hepatitis, 74, 179 Viral Proteins, 16, 19, 34, 61, 179 Virion, 20, 43, 179 Virulence, 7, 8, 10, 18, 19, 20, 22, 24, 32, 38, 39, 42, 44, 49, 75, 128, 171, 179 Virulent, 16, 73, 75, 77, 179 Vitro, 10, 28, 179 Vivo, 43, 179 Volvulus, 70, 179 Vomitus, 11, 179 W Water Intoxication, 61, 179 Wheezing, 157, 179 White blood cell, 88, 124, 133, 140, 153, 155, 158, 160, 164, 179 Withdrawal, 37, 179 Wound Infection, 109, 179 X Xenograft, 124, 179 X-ray, 9, 27, 40, 142, 152, 160, 168, 179, 180 X-ray therapy, 152, 180 Y Yeasts, 143, 152, 164, 180

Index 193

Z Zoonoses, 168, 180

Zymogen, 132, 167, 180

194

Gastroenteritis

Index 195

196

Gastroenteritis