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

ESOPHAGITIS 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., 1960Esophagitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00422-4 1. Esophagitis-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 esophagitis. 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 ESOPHAGITIS ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Esophagitis .................................................................................... 9 The National Library of Medicine: PubMed ................................................................................ 44 CHAPTER 2. NUTRITION AND ESOPHAGITIS ................................................................................... 87 Overview...................................................................................................................................... 87 Finding Nutrition Studies on Esophagitis................................................................................... 87 Federal Resources on Nutrition ................................................................................................... 88 Additional Web Resources ........................................................................................................... 89 CHAPTER 3. ALTERNATIVE MEDICINE AND ESOPHAGITIS............................................................. 91 Overview...................................................................................................................................... 91 National Center for Complementary and Alternative Medicine.................................................. 91 Additional Web Resources ........................................................................................................... 94 General References ....................................................................................................................... 95 CHAPTER 4. PATENTS ON ESOPHAGITIS ......................................................................................... 97 Overview...................................................................................................................................... 97 Patents on Esophagitis................................................................................................................. 97 Patent Applications on Esophagitis ........................................................................................... 103 Keeping Current ........................................................................................................................ 104 CHAPTER 5. BOOKS ON ESOPHAGITIS ........................................................................................... 105 Overview.................................................................................................................................... 105 Book Summaries: Federal Agencies............................................................................................ 105 Book Summaries: Online Booksellers......................................................................................... 110 Chapters on Esophagitis............................................................................................................. 110 CHAPTER 6. MULTIMEDIA ON ESOPHAGITIS ................................................................................ 115 Overview.................................................................................................................................... 115 Video Recordings ....................................................................................................................... 115 CHAPTER 7. PERIODICALS AND NEWS ON ESOPHAGITIS ............................................................. 117 Overview.................................................................................................................................... 117 News Services and Press Releases.............................................................................................. 117 Newsletter Articles .................................................................................................................... 119 Academic Periodicals covering Esophagitis ............................................................................... 122 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 125 Overview.................................................................................................................................... 125 NIH Guidelines.......................................................................................................................... 125 NIH Databases........................................................................................................................... 127 Other Commercial Databases..................................................................................................... 129 APPENDIX B. PATIENT RESOURCES ............................................................................................... 131 Overview.................................................................................................................................... 131 Patient Guideline Sources.......................................................................................................... 131 Finding Associations.................................................................................................................. 133 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 135 Overview.................................................................................................................................... 135 Preparation................................................................................................................................. 135 Finding a Local Medical Library................................................................................................ 135 Medical Libraries in the U.S. and Canada ................................................................................. 135 ONLINE GLOSSARIES................................................................................................................ 141 Online Dictionary Directories ................................................................................................... 143

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ESOPHAGITIS DICTIONARY................................................................................................... 145 INDEX .............................................................................................................................................. 205

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

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

Bile Reflux and Oesophagitis Source: European Journal of Gastroenterology and Hepatology. 13(1): 1-3. January 2001. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London SE1 1GB, UK 44(0)20-7940-7502. Fax: 44(0)20-7940-7574. Website: http://www.eurojgh.com/. Summary: Experimental data suggest that bile acids and trypsin are noxious to the esophageal mucosa and that their damaging potential depends on pH. The injurious concentrations are, however, higher than those usually observed in the human esophagus. This article explores the interplay between bile reflux (return of stomach contents to the esophagus) and esophagitis. Direct measurement of bile acids and trypsin is difficult and various methodologies have been used to measure

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duodenogastric or duodenogastroesophageal reflux; all of them having technical limitations. Whereas available data as to the extent of duodenogastric reflux (return of the contents of the duodenum or first part of the small intestine, back to the stomach) in gastroesophageal reflux disease (GERD) are controversial, most observations show that reflux of both acid and duodenal contents occur simultaneously in most reflux episodes. This article also comments on another article published in this issue of the Journal in which Marshall et al report that exposure of the gastric fundus to duodenal contents as assessed by bilirubin monitoring is similar in GERD patients with varying degrees of esophageal mucosal injury and in healthy controls. 19 references. •

Refractory Peptic Lesions: Therapeutic Strategies for Ulcers and Reflux Esophagitis that Resist Standard Regimens Source: Postgraduate Medicine. 93(4): 143-163. March 1993. Summary: Generally, ulcers and erosive reflux esophagitis heal after a couple months of therapy with agents that inhibit gastric acid secretion and bolster mucosal defense mechanisms. In this article, the author summarizes the approach to therapy for patients resistant to standard therapy. Such therapy includes use of high-dose regimens, use of a stronger agent or one with a different mechanism of action, triple-drug therapy for concomitant Helicobacter pylori infection, and surgery when necessary. The author also provides evidence from the literature supporting the effectiveness of these techniques. 1 table. 19 references. (AA).

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Long-Term Therapy for Reflux Esophagitis (editorial) Source: New England Journal of Medicine. 333(17): 1148-1150. October 26, 1995. Summary: In this editorial, the author explores current options for long term therapy for reflux esophagitis. Topics include symptoms of reflux esophagitis; their management with antacids and lifestyle modifications; maintenance therapy used to prevent recurrent symptoms and esophagitis; and the indications for antireflux surgery. The author then comments on a study, reported elsewhere in the Journal, in which researchers combined an acid-suppressing medication with a prokinetic drug as one of various maintenance regimens used for reflux esophagitis. The author concludes that combination therapy with an H2-receptor antagonist or a proton-pump inhibitor and a prokinetic agent is reasonable for healing and maintenance in patients who have incomplete symptomatic improvement or mucosal healing with single-drug therapy. Combination therapy should be limited to situations in which the added clinical benefit has been shown to justify the added cost. 16 references.

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Rationale for Continuous Maintenance Treatment of Reflux Esophagitis Source: Archives of Internal Medicine. 155(14): 1465-1471. July 24, 1995. Summary: In this review article, the authors investigated the rationale for continuous maintenance treatment of reflux esophagitis, a chronic process associated with frequent episodes of relapse in many patients. They note the accumulating evidence that continuous treatment of patients with erosive esophagitis effectively maintains symptomatic remission and absence of esophageal erosions. The authors investigated a number of questions concerning the natural history and complications of erosive esophagitis and the need for maintenance treatment for patients with severe manifestations of disease. They also studied the impact of continuous maintenance treatment on the natural history of reflux esophagitis and its complications. 2 tables. 48 references. (AA-M).

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Acid Reflux is a Poor Predictor for Severity of Erosive Reflux Esophagitis Source: Digestive Diseases and Sciences. 47(11): 2565-2573. November 2002. Contact: Available from Kluwer Academic Publishers. Customer Service Department, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: It is unknown which factors determine the severity of mucosal damage in gastroesophageal reflux disease (GERD). This article reports on a study that tested whether the amount of esophageal acid exposure could predict the severity of esophageal injury in erosive reflux esophagitis. A total of 644 outpatients with symptomatic GERD underwent an esophagogastroduodenoscopy followed by esophageal manometry and 24 hour pH monitoring. GERD was graded according to the endoscopic severity of mucosal damage as no erosions, single erosions, confluent erosions, esophageal ulcers, and strictures. The authors also assessed the influences of demographic characteristics, social habits, endoscopic anatomy, and various parameters of esophageal function tests on the severity of erosive reflux disease. No clear-cut association between the amount of acid reflux and severity of erosive reflux esophagitis could be established. All individual parameters of esophageal pH monitoring, such as upright or supine (lying down) acid contact time, frequency of all or only long reflux episodes, and an overall summary score of pH-metry, revealed no or only a weak correlation with the severity grade of erosive reflux esophagitis. Similarly, the pressure of the lower esophageal sphincter was only slightly more decreased in patients with extensive erosive esophagitis as compared to subjects without esophageal erosions. In analyses, the presence of hiatus hernia was a stronger predictor of disease severity than any of the other parameters. The authors conclude that factors other than exposure of the esophageal mucosa to acid must contribute to the development of erosive esophagitis. 4 figures. 3 tables. 32 references.

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Pill Esophagitis Source: Journal of Clinical Gastroenterology. 28(4): 298-305. June 1999. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1550, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Summary: Oral medications are most commonly administered as nonchewable tablets or capsules (pills). Injuries occur when caustic medicinal pills dissolve in the esophagus rather than passing rapidly into the stomach as intended. This article reviews 979 cases of pill esophagitis due to nearly 100 different medications. Most patients suffer only self limited pain, but esophageal hemorrhage, stricture, and perforation can occur, and fatal injuries have been reported. Types of pills discussed include antibiotics and antiviral pills; aspirin and other nonsteroidal antiinflammatory drugs; potassium chloride, quinidine, ferrous sulfate or succinate, and alprenolol (a beta blocker); and alendronate and pamidronate. The author concludes that the incidence of this iatrogenic injury can be reduced but not eliminated by emphasizing the importance of taking pills while upright and with plenty of fluids. In addition, pills implicated as causing frequent or severe esophageal injury should be avoided in bedridden patients or those with esophageal compression, stricture, or dysmotility. 4 tables. 39 references. (AA-M).

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Clinicopathologic Features of Esophagitis in Children Source: Gastrointestinal Endoscopy Clinics of North America. 11(4): 683-715. October 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: The esophagus traditionally has been considered a simple conduit for over 50 tons of foodstuffs ingested during a lifetime. However, when the innate protective mechanisms of the esophagus are overcome by an injurious agent, an inflammatory process ensues and the clinicopathologic features of esophagitis are manifest. This article explores these features as they arise in children. The article begins with a review of esophageal histology, esophageal protective mechanisms, and methods of evaluation, including gross inspection, mucosal biopsy, endoluminal ultrasound, and optical coherence tomography. The author then focuses on features of several manifestations, including peptic disease, duodenogastroesophageal reflux (DGER), Crohn's disease (CD), and infections. In addition, a relatively new, but increasingly recognized entity, eosinophilic esophagitis (EE) is highlighted. For each condition, the author reviews diagnostic criteria, epidemiology, treatments, and prognosis. 3 figures. 4 tables. 138 references.

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Increased Gastric Acid Secretion After Helicobacter Pylori Eradication May Be a Factor for Developing Reflux Oesophagitis Source: Alimentary Pharmacology and Therapeutics. 15(6): 813-820. June 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The role of acid secretion in reflux esophagitis, which may develop after Helicobacter pylori eradication, is not well known. This article reports on a study undertaken to investigate the participation of altered gastric (stomach) acid secretion and the presence of hiatal hernia in the development of reflux esophagitis after eradication therapy for H. pylori. A total of 105 patients with H. pylori infection, but without reflux esophagitis at the time of eradication therapy, were followed prospectively for 7 months after the clearance of this microorganism. Gastric acid secretion was assessed by endoscopic gastrin test and the presence of hiatal hernia was assessed by endoscopy. Reflux esophagitis developed in 11 out of 105 (10.5 percent) patients when examined at 7 months after the eradication therapy. The incidence was correlated significantly with the increase in gastric acid secretion after the eradication of H. pylori and was significantly higher in the patients with hiatal hernia (20 percent) than in those without it (0 percent). The authors conclude that increased acid secretion after H. pylori eradication is an important risk factor of reflux esophagitis, especially in patients with hiatal hernia. 3 figures. 41 references.

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Esophagitis Associated With the Use of Alendronate Source: New England Journal of Medicine. 335(14): 1016-1059. October 3, 1996. Summary: This article describes three patients who had severe esophagitis shortly after starting to take alendronate. Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobisphosphonates can irritate the upper gastrointestinal mucosa. The authors also analyze adverse esophageal effects

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reported to Merck, the manufacturer, through postmarketing surveillance. As of March 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1,213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 described in this article, adverse effects were categorized as serious or severe. Thirtytwo patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. Appended to the article are two related letters, each with references. 2 figures. 1 table. 35 references. (AA-M). •

Curing Helicobacter Pylori Infection in Patients with Duodenal Ulcer May Provoke Reflux Esophagitis Source: Gastroenterology. 112(5): 1442-1447. May 1997. Summary: This article reports on a study undertaken to investigate whether cure of the infection increases the risk of reflux esophagitis. The authors note that their previous work shows that cure of Helicobacter pylori infection leads to the disappearance of acidneutralizing substances. Also, patients with ulcer after cure may gain weight. In this study, patients with duodenal ulcer without reflux esophagitis at the time of Helicobacter treatment were followed up prospectively after cure of the infection (n = 244) or after diagnosis of persisting infection (n = 216). All patients underwent endoscopy at 1 year intervals or when upper gastrointestinal symptoms recurred. H. pylori infection was assessed by rapid urease test and histology. The estimated incidence of reflux esophagitis within 3 years was 25.8 percent after cure of the infection and 12.9 percent when the infection was ongoing. Patients who developed reflux esophagitis after the cure had a more severe body gastritis before cure, gained weight more frequently after cure, and were predominantly men. The authors propose the following hypothesis: certain subjects with high gastric acid secretion are at risk for development of reflux esophagitis; however, when these subjects are infected by H. pylori, duodenal ulcer develops instead. The infection exerts a protective effect on the esophagus, probably mediated by the ammonia buffer produced by H. pylori and refluxing in the esophagus. They conclude that patients with duodenal ulcer whose Helicobacter infection has been cured should carefully watch their dietary habits and body weight so as not to develop reflux esophagitis. 2 figures. 1 table. 54 references. (AA-M).

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Endoscopic Assessment of Oesophagitis Source: Gullet. 1(2): 63-67. 1990. Contact: Available from Churchill Livingstone. 1560 Broadway, 7th Floor, New York, NY 10036. (212) 819-5400. Summary: This article reviews the endoscopic assessment of esophagitis. After a discussion of the importance of diagnosis and classification, the authors consider the problems with endoscopic classifications and propose a new endoscopic classification. The authors stress that for research purposes it is preferable to use a classification system that can separate the pathologically distinct lesions of columnar metaplasia,

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ulceration, stricture formation, and epithelial erosion, and grade them independently. 2 figures. 25 references. •

Complications of Gastroesophageal Reflux Disease: Esophagitis, Acid Laryngitis, and Beyond Source: Postgraduate Medicine. 100(5): 95-97, 100, 106, 108, 113. November 1996. Summary: This article, the second of a four-part series on peptic acid disease, describes the most common esophageal and extraesophageal complications of gastroesophageal reflux disease (GERD). The authors also discuss various treatment options, emphasizing early, accurate diagnosis as crucial in appropriate treatment choice. Reflux of gastric contents can cause esophageal mucosal abnormalities, such as ulcers and peptic strictures, as well as pulmonary and otolaryngologic symptoms, including refluxinduced asthma and acid laryngitis. Left untreated, some complications can lead to more severe disorders, such as esophageal adenocarcinoma that develops in patients with Barrett's esophagus. The authors stress that accurate recognition of these diverse manifestations allows improved identification of patients at risk for reflux-related disorders and aids in proper evaluation and treatment. 1 table. 19 references. (AA-M).

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Heartburn and Reflux Oesophagitis (editorial) Source: Journal of Gastroenterology and Hepatology. 15(1): 1-2. January 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: This editorial comments on an accompanying article about heartburn and reflux esophagitis in a population in Australia. The authors disagree with some of the researchers' definitions, particularly as the study equates heartburn with gastroesophageal reflux disease (GERD). The editorial authors, however, agree that there is a high prevalence of dyspepsia in the Australian community and GERD is a large contributory component. The editorial than addresses some of the implications that result from this conclusion. Topics covered include symptomless reflux, cancer of the esophagus, Barrett's esophagus and reflux, and the use of antisecretory drugs to prevent the complications of esophageal reflux. The editorial comments on a major clinical and epidemiological puzzle in this arena: an epidemic of adenocarcinoma of the lower third of the esophagus has developed. This epidemic began just before the introduction of proton pump inhibitor drugs, which are a major means of managing the symptoms of reflux disease. There is no proof of the linkage involved or whether aggressive management of GERD is of more than symptomatic benefit. The authors call for more and better epidemiological studies into the mysteries of reflux and its complications. 9 references.

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Impact of Omeprazole and Laparoscopy Upon Hiatal Hernia and Reflux Esophagitis Source: Journal of the American College of Surgeons. 183(4): 413-418. October 1996. Summary: This review article analyzes the treatment successes on hiatal hernia and reflux esophagitis that are attributable to omeprazole and laparoscopy. Both approaches challenge the accepted multimodal, nonoperative therapy of the past two decades and the reproducible efficacy of the open fundoplication procedure. As a proton pump blocker, omeprazole decreases gastric acidity by directly blocking acid production. Omeprazole has a long duration of acid suppression that does not appear to affect

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gastroesophageal sphincter function or gastric motility. However, long-term use of omeprazole is questionable in terms of both safety and efficacy. The authors note that operative therapy, especially if minimally invasive (as in laparoscopy) is being more widely practiced. Laparoscopic Nissen fundoplication (LNF) has proved to be a very safe operation overall and the principles of reconstruction of the lower esophageal sphincter, which have been learned from open techniques, can be strictly maintained with the minimally invasive approach. The authors conclude with a call for additional studies to fully evaluate the clinical effectiveness of LNF and to define the 'learning curve' required for physicians. 6 tables. 46 references.

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

Project Title: 13 C SPIRULINA BREATH TEST TO MEASURE GASTRIC EMPTYING Principal Investigator & Institution: Murray, Joseph A.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: Our hypotheses are that a simple nonradioactive breath test can identify GERD patients who have delayed gastric emptying; gastric emptying is similar in a referral group of patients with gastroesophageal reflux disease as compared to those community based who self report GERD symptoms; and delayed gastric emptying in GERD is more associated with dyspeptic symptoms than the severity of frequency of GERD symptoms. The specific aims of the study are to validate the breath test method with scintigraphy in patients with delayed gastric emptying; to compare gastric emptying obtained from patients with GERD with the data obtained in healthy subjects; to compare the gastric emptying rates between patients seen in a referral population with GERD with a community based sample of subjects with GERD symptoms; and to correlate the degree of delayed gastric emptying with the severity and frequency of GERD and dyspeptic symptoms and the presence of complications of GERD if any. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

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Project Title: ACID SUPPRESSION EFFECT ON LASER TREATMENT OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Horwitz, Brenda; Temple University 406 Usb, 08345 Philadelphia, Pa 19122 Timing: Fiscal Year 2002 Summary: The aims of this protocol are to determine whether the normal lining of the esophagus in patients with Barrett's epithelium (a premalignant condition) can be restored by ablating the abnormal mucosa with endoscopic laser therapy and to determine whether the restoration of normal esophageal mucosa can be accelerated and prolonged by suppressing acid within the esophagus with medications vs Nissen fundoplication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AIRWAY PROTECTION AGAINST ASPIRATION OF GASTRIC CONTENT Principal Investigator & Institution: Shaker, Reza; Professor and Chief; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: A large number of pulmonary and aerodigestive tract disorders, ranging from aspiration pneumonitis, and lung abscesses to benign inflammatory lesions of the larynx and aerodigestive tract are caused by misdirection of gastric content into the respiratory system. The mechanisms of airway protection during retrograde transit of gastric content through the esophagopharyngeal lumen is not completely understood. In addition, although substantial information is available regarding the volume clearance of the aspirated material by the pulmonary structures, the defense mechanisms of the alveolar and bronchial linings against aspirated gastric acid remains unclear. Because of multisystem/organ involvement, systematic investigation of these mechanisms in health and disease conditions requires expertise from multiple disciplines. For this reason, during the past three years a concerted multidisciplinary, multidepartmental effort with participation of investigators from the Departments of Medicine, Otolaryngology, and Radiology was organized at the Medical College of Wisconsin Dysphagia Institute to systematically address these issues. The long-term objective of this program project is to provide the basis for preventive and/or therapeutic interventions in the future through the understanding of the central neural control and peripheral protective mechanisms against retrograde aspiration. All of the projects in this program share the common interest of identifying, characterizing, and quantitating the mechanisms that contribute to the protection of the airway against aspiration of gastric content in health and disease. The theme of this program project grant encompasses the function of the gastroesophageal junction as it relates to escape of gastric content into the esophagus, the significance of esophagopharyngeal, esophagolaryngeal, and pharyngolaryngeal reflexes in the closure mechanism of the tracheal inlet in response to gastroesophageal and esophagopharyngeal reflux and vomiting, and the role of bronchoalveolar defense mechanisms against acid alkaline and water exposure. The proposed program includes four projects and the administrative core. Projects 1 and 2 address the issue of extrapulmonary defense mechanisms against retrograde aspiration. Project 3 addresses the intrapulmonary defense mechanism against aspirated gastric content. Project 4 examines the mechanisms of airway protection during vomiting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AIRWAY PROTECTION DURING VOMITING Principal Investigator & Institution: Lang, Ivan M.; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002 Summary: Vomiting is a complex motor behavior that requires the coordinated action of musculature within the gastrointestinal and aerodigestive tracts. The mechanisms of airway protection during vomiting have not been studied and are presently unknown. This is in contrast to an extensive body of literature providing information on airway protective mechanisms operational during swallowing. Acute and chronic animal models will be utilized to study the role of the laryngeal, pharyngeal and hyoid muscles during vomiting. Investigation of the associated movements of the tongue base, hyoid bone, cricoid and thyroid cartilage, and epiglottis will also be studied. The action of these aerodigestive muscles will be temporally correlated with the action of the esophagus and gastrointestinal tract, and lower respiratory musculature. Finally, the relative contribution of peripheral reflexes and direct central nervous system control over the motor events that comprise vomiting will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANATOMIC AND MECHANICAL VARIABLES OF THE EGJ IN GERD Principal Investigator & Institution: Pandolfino, John E.; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term objective of this research proposal is to understand the role of anatomical and mechanical variables of the esophagogastric junction (EGJ) in the pathogenesis of gastroesophageal reflux disease (GERD). The candidate is currently in the first year of a tenure track faculty appointment in the Division of Gastroenterology and Hepatology at Northwestern University Medical School. He is seeking support for full time mentored research. His mentor, Dr. Peter Kahrilas is an NIH funded internationally-recognized expert on esophageal physiology and division head in the department of Gastroenterology and Hepatology. In addition, the candidate will be enrolled in the K30 sponsored Master of Science in Clinical Investigation Program at the Graduate School of Northwestern University. The proposed research study is to define the anatomical and mechanical variables of the EGJ as they relate to GERD. The EGJ is a complex anatomic zone whose functional integrity is sum of its many parts. To date, much of the research on the competence of the EGJ in GERD has been focused on the lower esophageal sphincter. Our hypothesis is that acquired anatomic changes inclusive of, but not restricted to hiatal hernia may alter the mechanical characteristics of the EGJ and affect the propensity to reflux. One such variable that will be studied is compliance. Increased compliance may exacerbate reflux in two ways: 1) lowering the incremental increase in intra-abdominal pressure required to open the relaxed or hypotensive EGJ, and 2) the relaxed EGJ may open wider than normal under a given physiological circumstance resulting in a reduced discriminative resistance for liquid as opposed to gas reflux. Compliance will be determined using a customized barostat technique and then correlated with hiatal hernia size, intraabdominal LES length, angle of His and gastroesophageal flap valve grade. In addition, we will be attempting to improve standard pH monitoring technique by measuring acid exposure at the SCJ and converting data to hydrogen ion concentration exposure. These

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changes will improve diagnostic accuracy of pH monitoring and also help determine the relationship between anatomical and mechanical variants and acid reflux. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANIMAL MODEL OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Chen, Xiaoxin; Chemical Biology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The aim of this project is to investigate the role of bile acids in the development of Barrett's esophagus (BE), and to develop an animal model for BE and esophageal adenocarcinoma (EAC). Our previous animal models, esophagoduodenal anastomosis (EDA) and esophagogastroduodenal anastomosis (EGDA), mimicked the development of EAC by introducing mixed reflux of gastric and duodenal contents into the rat esophagus. Nevertheless, the role of bile acids in the development of BE is still not clear. This project will address this issue with the following specific aims: 1. To generate rats with reflux containing different levels of bile acids, through dietary supplementation, mimicking the bile acids profile in the gastroesophageal refluxate of human BE patients. Reflux will be induced by cardioplasty in rats. These rats will be given AIN93Mbased diets containing 0.25%, 0.5%, 1% or 2% bile acids mixture that mimics the bile acids profile in the gastroesophageal refluxate of human BE patients. Trypsin (0.4 mg/ml) and lysolecithin (1 mg/ml) will also be given in drinking fluid. Four weeks later, histopathology and the bile acids profile in the esophageal mucosa will be analyzed. The pH, trypsin, lysolecithin and the bile acids profile in the esophageal and gastric contents will also be analyzed. These results will help us select two treatment conditions for the long-term study. 2. To determine the role of bile acids in the development of rat BE, and possibly EAC. Cardioplasty rats will be given AIN93M diets containing bile acids mixtures (concentrations determined in Aim 1) plus trypsin and lysolecithin in drinking fluid. The rats will be sacrificed at 10, 20, 40 and 60 weeks after surgery. The development of BE, BE with dysplasia, and possibly EAC will be analyzed and characterized. These studies are expected to determine the effect of bile acids on the formation of BE, and lead to the development of a novel animal model of BE and EAC. Such an animal model would provide a basis for future studies on the mechanism, prevention, and therapy of BE and EAC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BACTERIAL FLORA IN NORMAL ESOPHAGUS & REFLUX DISORDERS Principal Investigator & Institution: Pei, Zhiheng; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Gastroesophageal reflux (GERD) is a chronic inflammatory disease affecting millions of Americans leading to the development of gastric/intestinal metaplasia (Barrett's esophagus), which is a precursor for adenocarcinoma (Ca). Although data from the stomach and colon suggest that colonizing bacteria are essential in inflammation-induced cancer development, little is known about esophageal bacterial flora. The long-term goal of this project is to define the role of bacteria in the progression of GERD to Barrett's esophagus and Ca. Our hypothesis is that bacterial flora exist in the normal esophagus, changing in the

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evolution of GERD into Barrett's esophagus and Ca. The specific aims are to: 1) define at a population level the bacterial flora in the normal esophagus and the esophagus with GERD-related diseases, 2) define at a species level the bacterial flora in the normal esophagus and GERD-related diseases, 3) determine host humoral immune responses to esophageal bacteria in patients with GERD-related diseases and controls. To define bacterial flora at a population level. The total number of bacteria per biopsy will be determined by quantitative real-time PCR using universal bacterial 16S rDNA primers with DNA from each biopsy. Specimens from disease groups will be compared for bacterial density (square mm mucosa). To define the flora at a species level, biopsies will be analyzed using sequence-based universal bacterial16S PCR and cultivation. PCR products will be cloned and sequenced, and species identification accomplished by comparing the sequences with kno\\0'D bacterial 16S sequences. Biopsies also will be cultured in anaerobic, aerobic, and microaerobic conditions, and colonies biochemically defined to a species level. Each disease group will be compared for the species identified and their prevalence. Cultivable whole cell bacterial antigens will be used in ELISA to determine whether the hosts recognize their presence. Serum antibodies also will be examined using immonoblots to identify disease-specific antigens. Significance: (i) Bacterial flora in the GI tract play important roles in pathologic conditions including inflammation and neoplasia. The esophagus is the only part of the GI tract where little is known about the bacterial flora, and the proposed study will assess the existence and complexity of the flora. (ii) While GERD initially results from chemical damage, bacterial overgrowth may promote intestinal metaplasia of the esophagus. The proposed study allows qualitative and quantitative examination of this hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGICAL IMAGE GUIDED/ RESPIRATION GATED IMRT OF NSCLC Principal Investigator & Institution: Amois, Howard; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Lung cancer remains the most common cause of cancer death in the US with over 150,000 deaths per year. Radiation therapy (RT) is the main curative modality for inoperable non-small cell lung cancer (NSCLC). This study addresses the poor local control rates of conventional RT, where treatment success is constrained by: 1. Limits on radiation doses due to radiation pneumonitis, and for patients receiving concurrent chemotherapy(ChT), esophagitis. 2. Respiration-induced tumor motion, requiring larger treatment fields and increased treatment toxicity. 3. Uncertainties in tumor definition due to limited sensitivity and accuracy of CT imaging. 4. Uncertainties in RT treatment delivery and inability to confirm daily treatment accuracy. Previous studies have demonstrated the advantages of 3-D Conformal RT (3DCRT) and deep inspiration breath hold for reducing treatment uncertainties and normal tissue toxicities. In this proposal, significantly advanced technologies will be joined in an integrated approach to RT of NSCLC. These new strategies are: 1. Inverse Treatment Planning and Intensity Modulated RT for improved conformal normal tissue avoidance. 2. Respiratory Gating to control breathing motion during imaging, simulation, and treatment. 3. Improved tumor detection and delineation by combining FDG-PET and CT imaging. 4. Improved treatment verification using electronic portal imaging and megavoltage cone beam imaging. These new technologies will provide unprecedented accuracy in identifying and targeting tumors, and in minimizing normal tissue toxicity, thus permitting higher treatment doses. Our proposed clinical study

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targets 3 groups of surgically unresectable patients for escalation to the following maximum doses: (1) 99Gy to 'small' tumors; (2) 90Gy to 'large' tumors for patients ineligible for ChT, or who have previously received ChT; (3) 80 Gy RT for patients receiving concurrent ChT. We hypothesis that this high technology approach will permit treatment to higher doses without increasing normal tissue toxicity, and improve local control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAINSTEM ESOPHAGEAL - GASTRIC CONTROL REFLEXES Principal Investigator & Institution: Rogers, Richard C.; Professor; None; Lsu Pennington Biomedical Research Ctr 6400 Perkins Rd Baton Rouge, La 70808 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The esophageal distension-gastric relaxation response or "receptive relaxation reflex" [RRR] is an autonomic mechanism which normally increases gastric volume and reduces intragastric pressure to assure that swallowed food is efficiently transported to and retained by the stomach. There is a large body of descriptive literature which supports the existence of the RRR in a number of species including rats and humans. This reflex is mediated largely, is not exclusively by a vagal afferent-CNSvagal efferent pathway. Failure of this reflex mechanism has been held responsible for a number of serious swallowing and reflux disorders. This circuitry, which produces gastric relaxation, may also play a critical role in the perception of nausea and the production of emesis. Our preliminary results suggest that the central RR circuitry of esophageal vagal afferent connections with the nucleus of the solitary tract, pars centralis (NSTc] which, in turn, projects throughout the entire dorsal motor nucleus of the vagus [DMN]. DMN efferents which control the motility and compliance functions of the stomach are separable into two distinct vagal pathway. The other DMN projection to the stomach probably activates a non-adrenergic non-cholinergic [NANC] enteric circuit. Based on our preliminary physiological data we formulate the following hypotheses: the NSTc neurons activated by esophageal afferent input operate on these two separate DMN pathways to the stomach such that the muscarinic ["excitatory"] pathway is inhibited while the NANC ["inhibitory"] pathway is activated. The combination of effects produces a profound relaxation. Furthermore, we predict that a previously identified corticotrophin releasing hormone [CRH]- ergic CNS mechanism activated by psychological stress produces gastric stasis by activating RR circuit elements in the dorsal vagal complex. These predictions will be tested by a combination of in vivo and in vitro neurophysiological and immunocytochemical protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMORECEPTION AND SIGNAL PROCESSING IN VAGAL AFFERENTS Principal Investigator & Institution: Weinreich, Daniel; Professor; Pharmacol & Exper Therapeutics; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-MAR-1985; Project End 30-JUN-2007 Summary: (provided by applicant): Understanding the impact of airway inflammation on vagal afferents is of particular interest because these neurons play an important role in the life-threatening reflex bronchoconstriction that occurs during anaphylactic reactions. During these reactions, airway vagal afferents are excited and modified by unidentified products released from, or generated by, mast cell activation. Two functionally distinct populations of vagal afferents innervating the airway, nodose and

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jugular ganglion neurons (NGNs and JGNs) will be identified with retrograde fluorescence tracers and their electrophysiological and pharmacological properties studied before and following chronic allergic airway inflammation. We will also determine whether chemical communication between nodose somata is somatotopically organized and influenced by inflammation in vitro and in vivo. Airway projecting NGNs and JGNs will be studied in vitro using voltage clamp recording in conjunction with microfluorimetry to measure intracellular calcium. Calcium and second messengers will be analyzed and manipulated in order to clarify the signal pathway of NK-2 tachykinin receptor (NK2R)-mediated currents (Icat) unmasked by mast cell activation, or by serotonin. Icat channels will be characterized by their cation selectivity and single channel properties and compared to transient receptor potential channels (TRPC). NK2Rs signaling cascade to activate TRPC in HEK293 cells will be compared with NK2R pathway activating Icat in NGNs. These studies will add to our understanding of allergic inflammation-induced neuroplastic changes in vagal afferents. This study of the signal molecules and mechanisms underlying the neuroplasticity in vagal afferents will also shed new light on the pathobiology of myriad hypersensitivity and inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL TRIAL OF ACID REFLUX THERAPY IN ASTHMA Principal Investigator & Institution: Wise, Robert A.; Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Gastroesophageal reflux (GERD) is frequent in asthmatics with poor asthma control, often occurs without symptoms, and can induce bronchoconstriction. Poorly controlled asthmatics are often treated for GERD with drugs that suppress gastric acid, but this treatment is expensive and the benefit of such treatment is not established. The objective of this proposal is to conduct a multi-site randomized clinical trial testing the hypotheses that treatment of GERD with protonpump inhibitors will reduce the frequency of exacerbations in patients with inadequately controlled asthma. The proposed trial will enroll 400 asthmatics, ages 1860, who have poor asthma control on inhaled steroids, defined on the basis of excessive bronchodilator use, nocturnal awakenings, or frequent exacerbations. Participants will be randomly assigned to treatment with either a proton pump inhibitor, esomeprazole (Nexium) 40 mg BID, or matching placebo. The presence, severity, and temporal relationship of GERD to asthma symptoms will be documented with 24 hour ambulatory esophageal pH probe monitoring, but participants will be enrolled irrespective of the severity of GERD. The primary outcome measure is the proportion of participants who have exacerbations of asthma within a 6-month period defined by asthma diaries and interviews. Secondary outcome measures include asthma symptom and control scores, asthma-specific and generic health-related quality of life, GERD symptoms, health care use, pulmonary function, and airways reactivity. Pre-specified subgroup analyses will be conducted to determine if there are clinical or demographic characteristics that predict benefit from treatment of GERD in asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMBINATIONAL CHEMOPREVENTION OF ESOPHAGEAL ADENOCARCIN* Principal Investigator & Institution: Buttar, Navtej S.; Assistant Professor of Medicine; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905

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Timing: Fiscal Year 2004; Project Start 06-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Barrett's esophagus is a pre-malignant condition that predisposes to esophageal adenocarcinoma, which has one of the fastest rising incidence rates in the United States and has limited therapeutic options. THE LONGTERM GOAL of our lab is to develop mechanism-based, safe chemopreventive agents to prevent carcinogenesis in Barrett's esophagus. The mechanisms of carcinogenesis in Barrett's esophagus is not completely understood but esophageal refluxate containing bile salts is implicated in this process. Bile salts can activate several cellular pathways including the NFKB survival pathway and cyclooxygenase-2 (COX-2) leading to high levels of prostaglandins in the esophagus. We have shown that certain prostaglandins, in particular PGE2, are associated with the development of neoplasia in Barrett's esophagus and their inhibition by COX-2 inhibitors results in prevention of esophageal cancer in an animal model of Barrett's esophagus. Human studies are underway to assess the chemopreventive effect of COX-2 inhibitors. Combinational chemoprevention, whereby synergism can be achieved between two chemopreventive agents, represents an important development in the field of cancer prevention. Ursodeoxycholic acid (Urso) is another potential chemopreventive agent, which is a tertiary bile salt with an established safety profile. It inhibits NFKB activation as well as phospholipase A2 both of which act upstream of COX-2 enzyme and can therefore be a novel combinational chemopreventive agent with COX-2 inhibitors. We recently observed that Urso increases apoptosis, inhibits cell proliferation and decreases PGE2 production in Barrett's epithelial cells as well as potentiates the effect of COX-2 inhibitors on these parameters. Urso also inhibits PGE2 production and reduces the concentration of carcinogenic bile salts in the duodenum of an animal model with esophageal reflux. Based on these observations, we propose the novel and mechanistic HYPOTHESIS that inhibition of carcinogenic bile salt mediated PGE2 production by Urso will compliment the chemopreventive action of COX-2 inhibitors in Barrett's esophagus via a negative regulation of NFKappaB activation. To test this hypothesis, we have two SPECIFIC AIMS. First we will assess the rate of adenocarcinoma and PGE2 levels in the esophagus with a combination of Urso + COX-2 inhibitor treatment and compare it to either Urso or COX-2 inhibitor treatment alone. Secondly, we will examine if a decline in the levels of activated NFkB in the esophagus results in decreased levels of PGE2 and decreased risk of adenocarcinoma in the esophagus and assess whether the association is explained by Urso and or COX-2 inhibitor treatment. We propose an in vivo study using an established model of Barrett's esophagus and adenocarcinoma. A successful outcome of this hypothesis-driven preclinical study will provide adequate information and rationale to initiate clinical trials involving the use of combinational Urso and COX-2 inhibitors in prevention of esophageal adenocarcinoma and to explore mechanistic steps involved in this process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPARISON OF TWO DOSES OF BOTULINUM TOXIN FOR THE TREATMENT OF ACHALASIA Principal Investigator & Institution: Pasricha, Pankaj J.; Chief; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002 Summary: The purpose of this research study is to evaluate the effectiveness and safety of a new treatment for achalasia of the lower esophageal sphincter. The esophagus is my food tube, and the muscle called a sphincter separates this tube from my stomach. Achalasia means that this sphincter muscle is too tight and fails to relax, so food does

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not pass properly into my stomach. As a result, I may experience difficulty swallowing, regurgitation, and weight loss. The new treatment being studies compares two different doses of botulinum toxin type A (Bo Tox(R)) to keep the sphincter open. This procedure involves injecting Bo Tox(R) into the sphincter muscle to open it. This procedure has been studied by Dr. Pasricha in patients with achalasia, in which Bo Tox(R) 80 units was injected into their esophageal sphincter during an endoscopy. After six months, 65% of the patients had experienced relief and still did not have their achalasia symptoms. After 1 year, 424 of the patients did not have symptoms. It is thought that using Bo Tox(R) will provide a safer and easier alternative to the current treatments. The current treatments for achalasia include balloon dilation (widening) of the esophageal sphincter, or surgery. This study will also determine whether using Bo Tox(R) in higher doses will cause toxicity (overdose), and will relieve the symptoms of achalasia for longer time periods. Botulinum toxin type A (Bo Tox(R)) is a product cultured from Clostridium botulinum, a toxin which when found in nature is known to be poisonous, and causes muscle paralysis. However, this preparation has been specially prepared for use as a medicine, and is commonly used to treat patients who have eye problems, such as droopy eyelids, for which has FDA approval. The use of Bo Tox(R) is not approved by the Food and Drug Administration (FDA) for use in achalasia, but it is used to treat this condition at some medical centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF A COMPREHENSIVE PATIENT MANAGEMENT SYSTEM Principal Investigator & Institution: Soll, Andrew H.; Cpm Systems, Inc. 1665 Michael Ln Los Angeles, Ca 90272 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 30-SEP-2002 Summary: Comprehensive Patient Management Systems (CPMS) is designed to manage information and improve health outcomes by enhancing patient assessment. CPMS systematically captures direct patient input at initial, exit and revisit sessions on symptoms, psychosocial variables, quality of life (QOL) and treatment response. In Phase I, a prototype was developed that analyzed symptom patterns and generated a problem-oriented health summary for physician review and editing as a clinical report. Patient acceptance of CPMS was enthusiastic across the full range of computer experience. Physicians found the report accurate and useful. In Phase II, the system will be re-engineered for commercial application. Clinical applications will be refined for a general medical assessment, quality management and patient satisfaction. CPMS will undergo internal testing and beta-testing in clinic settings. The goal remains not to make diagnoses, but to efficiently collect and manage patient data thereby facilitating care and supporting patient-physician communication. The value to patients is greater involvement in their care. The value to healthcare providers is increased efficiency, more comprehensive assessment and the opportunity to self-monitor and improve outcomes. The value to research organizations is a tool for rigorous outcome trials in practice settings. PROPOSED COMMERCIAL APPLICATIONS: This software system is designed to enhance and capture patient assessment, quality of life (QOL) measurement, and physician process. Once feasibility has been established, commercial value will stem from use as an outcome tool in controlled trials and as a mechanism to enhance and measure patient outcomes in practice settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIFFERENTIAL CORTICAL ACTIVATION IN RESPONSE TO VISCERAL & SOMATIC STIMULATION Principal Investigator & Institution: Chey, William D.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF INFLAMMATION ON ESOPHAGEAL MOTILITY Principal Investigator & Institution: Moreland, Robert S.; Professor; Medicine; Drexel University College of Medicine 245 N 15Th St Philadelphia, Pa 19102 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENHANCED CRAD FOR ESOPHAGEAL ADENOCARCINOMA Principal Investigator & Institution: Yamamoto, Masato; Surgery; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Esophageal adenocarcinoma is now the fastest growing cancer category in western men. Additionally, the prognosis of locally advanced disease has remained static despite current management advances. These facts clearly indicate the necessity of developing novel therapeutic approaches for esophageal adenocarcinoma. Even though conditionally replicative adenoviruses (CRAds) offer a novel and potent modality to approach solid tumors of the gastrointestinal tract, esophageal adenocarcinoma cells are extremely resistant to adenoviral infection due to minimal expression of the adenoviral primary receptor (coxsackie-adenovirus receptor, CAR). Furthermore, the lack of promoters with selectivity for esophageal adenocarcinoma has hindered the construction of CRAds that can selectively replicate in target tumor cells to achieve a useful therapeutic index for clinical utility. Lastly, absence of a non-invasive in vivo imaging method to detect CRAd replication and spread has hampered an understanding of CRAd biology in vivo. To achieve full therapeutic potential of CRAds for esophageal adenocarcinoma, we propose the construction of promoter-driven, infectivity-enhanced CRAds with imaging capabilities. To address the first issue, we have identified three promising promoters that exhibit favorable "tumor versus liver" and "tumor versus normal mucosa" differentials which are critical for utility in an adenoviral context. As well, we have developed methods to alter the tropism of adenoviruses, thereby achieving infectivity enhancement of tumor target ceils. The incorporation of an RGD4C motif in the HI loop of the fiber-knob region and Ad5/3 chimeric fiber modification has been shown to dramatically improve the infectious potency of adenovirus on esophageal adenocarcinoma cells. These findings offer solutions to the problem of esophageal adenocarcinoma cell resistance to adenoviral infection. In addition, we will configure optical and radiological imaging functions into our infectivity enhanced CRAds driven by optimal promoter. These features provide minimally invasive detection of CRAd replication and spread in a clinical setting, serving as a monitoring system with relevance to patient safety. Thus, it is obvious that infectivity-enhanced CRAds controlled by an optimal promoter element and possessing an imaging capability will be a therapeutic agent with great clinical

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utility for esophageal adenocarcinoma. The applicability of these modalities will be established from both toxicological and tumoricidal effect standpoints along with confirmation of CRAd functionality by optical and radiological imaging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGIC CASE-CONTROL STUDY OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Shaheen, Nicholas J.; Assistant Professor; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: The long-term objectives of this project are to advance the understanding of the pathophysiology and management of Barrett's esophagus, and to achieve further formal training in epidemiology and outcomes research for the applicant. Dr. Shaheen, the applicant, is an Assistant Professor at UNC and is Co-Director of the Center for Esophageal Diseases. His mentor, Dr. Robert Sandler, is an established GI epidemiologist, and Director of the Center for Gastrointestinal Biology and Disease (CGIBD). They propose a combined didactic and clinical research experience, utilizing the resources of the UNC School of Public Health, the GI Division and the CGIBD to foster Dr. Shaheen's demonstrated interest in outcomes research. Dr. Dawn Provenzale from Duke University will also provide instruction and mentoring, as well as expertise in the subject area, Barrett's esophagus. The study proposed as part of the clinical training is a case-control study of Barrett's esophagus. Barrett's esophagus is a premalignant lesion of esophageal adenocarcinoma, a usually lethal cancer whose incidence is increasing in epidemic proportions. Barrett's is associated with gastroesophageal reflux. Because we cannot adequately stratify risk for Barrett's among those with reflux, authorities recommend that all those with chronic reflux undergo endoscopic screening for Barrett's. Better stratification of Barrett's risk would allow for more targeted usage of screening endoscopy. The specific aims of this study are: 1) To evaluate the relationship between obesity and Barrett's, 2) To assess the role of H. pylori infection and Barrett's, 3) To assess the predictors for dysplasia among those with Barrett's, and, 4) To assess the quality of life of those with Barrett's compared to controls with reflux. The study will recruit 175 cases with reflux symptoms and Barrett's esophagus, and 350 controls with reflux symptoms and no Barrett's who present for endoscopy at UNC. Participants will complete a telephone interview assessing demographics, health habits, risk factors for early H. pylori acquisition, and reflux symptoms. Also, subjects will be administered a measure of quality of life, the Health Status Questionnaire, and a psychological profile, the Revised Hopkins Symptom Checklist. Subjects will undergo assessment of height, weight, hip and waist circumference. Data analysis will compare body mass and fat distribution, as well as risk factors for early H. pylori acquisition, between cases and controls. Subjects with Barrett's and dysplasia will be compared to those with Barrett's alone to assess for risk factors for dysplasia. Finally, by comparing subjects with Barrett's to controls with reflux, and controlling for severs of reflux, the impact of a Barrett's diagnosis on quality of life and psychological stress may be seen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESOPHAGUS

EPITHELIAL-REFLUXATE

INTERACTIONS

IN

BARRETT'S

Principal Investigator & Institution: Triadafilopoulos, George; Medicine; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The major objective of our studies is to understand the molecular changes that occur in response to acid and bile exposure in normal and Barrett's esophagus (BE). BE is a metaplastic premalignant condition of the esophagus that is associated with an increased risk of up to 30-fold of developing esophageal adenocarcinoma. Exposure of the esophagus to the duodeno-gastro-esophageal (DGE) refluxate, important constituents of which include acid and bile, is a major risk factor for the development of BE and subsequent esophageal adenocarcinoma. Our overall hypothesis is that identifying acid and bile stimulated up- or down regulated genes in the normal esophagus and Barrett's epithelium, and characterizing the signaling pathways that are involved, should provide potential diagnostic and therapeutic targets and essential clues regarding the mechanisms of esophageal metaplasia and abnormal cell proliferation in BE. Our specific aims and hypotheses are: (i) Use a human microarray approach, ex vivo, to identify the genes that are modified in response to acid or bile in normal esophagus, BE and duodenum. This aim is based on the hypothesis that the DGE refluxate modulates the genetic program of normal esophageal, BE and duodenal epithelia differently, in a refluxate constituent-dependent fashion. (ii) Identify the acid or bile-induced modified genes in squamous esophageal and Barrett's cell lines. This aim is based on the hypothesis that tissue cultured cell lines, due to their ability to provide an unlimited supply of RNA for gene profile analysis, may provide complimentary information to that obtained using ex vivo biopsies. (iii) Study the signaling cascades of protein kinase C, Cox-2, and Src kinase that are involved in acid/bile-induced stimulation, and define their potential interactions. This aim is based on the hypothesis that characterizing the signaling pathways that are involved in acid and bile stimulated cell proliferation complements the microarray gene profiling strategies and may provide potential complimentary targets for decreasing the risk of dysplasia and adenocarcinoma in BE. Overall, our study seeks to define the molecular signals that play a role in developing metaplasia and that regulate the acid- and bilemediated responses in the esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESOPHAGEAL CYTOPROTECTION--AGENTS AND MECHANISMS Principal Investigator & Institution: Orlando, Roy C.; Professor of Medicine & Chief; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-AUG-2004 Summary: The long term goal of this proposal is to understand the pathogenesis of the human disease, reflux esophagitis (RE), and this approached mechanistically and from the relatively uncommon vantage point of the target tissue, the esophageal epithelium (EE). In this grant, we focus on the barrier properties of the EE, and especially that of the intercellular junctions (ICJs). The ICJs have importance as an essential defense against H+ entry into EE and as the initial target for H+ attack and damage that culminates in esophagitis. Therefore, one major goal is to characterize the barrier properties to select ions and molecules of the lumen-facing, apical cell membranes (ACMs) and ICJs using in vitro rabbit EE in Ussing chambers, and to determine how exposure to luminal acid alters these properties. Also, since many patients with RE have normal acid contact time on pH monitoring, experiments in Ussing chambered-EE are designed to identify (nonacidic) factors within the refluxate, meals and the esophageal inflammatory reaction that can contibute to breaking the barriers to H+ entry into EE, and for those identified, to localize the site of action to ACMs and/or ICJs and characterize, by pH-microelectrodes, the ability to lower pHi. Further, there is evidence to suggest that patients with RE have

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defects in (epithelial) barrier function, and that those with nonerosive esophagitis have damage localized to the ICJs. Since localization to the ICJs is key to validating our proposed pathogenesis of heartburn and esophagitis, another goal is to confirm, using in vivo PD measurements during salt superfasions, that this defect is localized to the ICJs. Moreover, there is a high rate of relapse following medical therapy and preliminary data suggest that this is attributable to persistent defects within the EE. Therefore, we hypothesize that the defects are due to persistent esophageal inflammation and studies proposed to correlate histologic esophagitis on endoscopic biopsy with relapse frequency after cessation of medical therapy. Also, defects in epithelial defense are sought by PD measurements during acid perfusion in asymptomatic elderly Caucasian males, a group at high risk for RE, and if found, to determine if the defect is in the barrier, and age or genetics related. Another goal is to use morphology (epifluorescence/confocal microscopy, freeze fracture, TEM, immunocytochemistry). Ussing chambers and SDS-PAGE technology, to study the structure/function of the ICJs in healthy EE and to assess the mechanisms of H+ damage. This effort coupled with the studies above should provide new insights into the pathogenesis of RE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESOPHAGEAL MOTILITY AND AIRWAY DEFENSES AMONG INFANTS Principal Investigator & Institution: Jadcherla, Sudarshan R.; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-AUG-2002 Summary: (provided by applicant): Feeding difficulties and airway-related complications in neonates, which contribute significantly to the infant mortality and morbidity with enormous socioeconomic consequences, might be related to motor functions of pharynx, esophagus, or stomach which may be dependent upon neural control and muscular function. Prematurity, perinatal asphyxia, and congenital abnormalities represent three important contributory factors to feeding difficulty among infants, who fail to thrive and chronically suffer from nutritional deprivation, gastroesophageal reflux, in addition to chronic lung disease and other life-threatening events. Our long-term objective is to define the mechanisms of feeding failure and airway compromise in developing infants, to pave way for evidence-based diagnosis and therapeutic intervention. Specific Aim 1 will determine maturational changes in the relationship between deglutition and airway safety. We will evaluate the basal and protective motor mechanisms involved in pharyngeal and esophageal phases of swallowing in developing infants during health and disease. Specific Aim 2 will investigate the mechanisms of esophageal and airway protection or compromise in infants with congenital foregut anomalies and neurologic disorders. Using wellestablished techniques developed at our Center, the innovative micromanometric water perfusion technique and a specially designed micromanometric catheter with sleeve sensor, we will measure pressure relationships at various levels within the foregut. Respiratory function measurements will simultaneously be recorded to to establish the relationship between esophageal motility and respiratory function in health and disease, and to ensure subject safety. In addition to ANOVA for repeated measures and students t-test, we will use growth curve analysis with a logistic model to permit the use of longitudinal grouped data. These studies will establish improved basal and protective esophageal motor function with development, and identify mechanisms of feeding failure and airway safety in infants.

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

Project Title: EVALUATION OF MINIMALLY INVASIVE SURGERY Principal Investigator & Institution: Rogers, Stanley J.; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Major advances have been made over the past decade developing minimallyinvasive endoscopic, surgical and radiographic procedures in an attempt to decrease mortality, morbidity, hospital stay and overall health care costs in treating patients with abdominal disorders. The treatment of these common gastrointestinal disorders needs to be studied in randomized controlled clinical trials. Given my training and experience in surgical endoscopy and minimally invasive surgery (laparoscopy), I propose studying in the context of randomized controlled clinical trials three distinct areas of gastrointestinal disease in which major advances have occurred employing laparoscopy, endoscopy and interventional radiological techniques. The three principal projects for this mentored clinical research are the following: 1. Randomized controlled clinical trial of laparoscopic cholecystectomy with laparoscopic common bile duct exploration versus endoscopic retrograde cholangiopancreatography with sphincterotomy followed by laparoscopic cholecystectomy for patients with common bile duct stone disease. 2. Laparoscopic anti-reflux surgery versus long-term administration of proton pump inhibitors (lanzoprasole) for moderate to severe gastroesophageal reflux disease. 3. Intra-arterial chemoembolization alone versus intra-arterial chemoembolization plus laparoscopic, ultrasound-guided radiofrequency ablation for non-resectable hepatocellular carcinoma. All three protocols involve minimally invasive surgery and other therapies studied in a prospective randomized controlled fashion. While the technical expertise, equipment and facilities used to perform these procedures have been developed around the world, few randomized controlled clinical trials exist that critically examine outcome parameters for a sufficient period of time to document efficacy, safety, improved survival and overall cost benefits in the treatment of these disorders. These three trials will allow such an evaluation of minimally invasive procedures used to treat patients with common gastrointestinal disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GASTRIC ENTEROCHROMAFFIN-LIKE CELL IN ULCER DISEASE Principal Investigator & Institution: Sachs, George; Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 30-APR-2004 Summary: Gastric acid secretion is a major factor in causation of GERD and peptic ulcer disease. H. pylori modifies secretion of gastrin and somatostatin and is also a major contributor to ulcerogenesis. Understanding of the pathways involved in stimulation of parietal and peptic cell function is important in defining the pathogenesis of ulcer disease. Studies of regulation of secretion have used various models. Intact animal studies have defined some neural pathways and endocrine and paracrine effectors. These models cannot usually define the cells directly involved in changes of gastric acid secretion. Isolated cell models have in general confirmed what has been found in animal models, but without high purity or video imaging the contribution of cell specific receptors and signaling has not been possible. To date, we have used video-imaging of calcium signals coupled with studies of histamine release to define receptors on the ECL cells at 85 percent purity and also shown Cai responses of individual G and D cells to

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ligands such as aromatic amino acids. With our recent (3 months) acquisition of a Zeiss confocal microscope, we now propose to continue these studies on isolated cells and now mainly to investigate more integrated models of gastric function, using isolated superfused fundic glands and segments of fundic epithelium, isolated perfused and superfused antral glands and antral segments. The responses of the individual cells in these models, i.e. ECL and fundic D cells, parietal and peptic cells for fundic models and G and D and peptic cells for antral models will enable studies of stimulation-secretion coupling as applied to endocrine-secretory cell coupling for the first time by direct visualization using appropriate dyes for Ca (mag-fluo-4) and pH (carboxy-SNARF-1) and acid secretion (acridine orange and 9-amino acridine). From this approach, the pathways involved with effects of PACAP, carbachol, CCK-8 and gastrin as possible neural or endocrine mediators of secretory stimulation and somatostatin, galanin, secretin and PYY as possible paracrine, neural or endocrine mediators of secretory inhibition will be determined. Preliminary confocal data, some of which are displayed in this application, show that this approach is technically feasible and conceptually rewarding. Hence this approach will provide additional insights into mechanisms of regulation of gastric secretion and enable illuminated interpretation of the pathophysiology of peptic ulcer disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GASTROESOPHAGEAL REFLUX AFTER LAPAROSCOPIC HELLER ESOPHAGOMYOTOMY Principal Investigator & Institution: Richards, William O.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GASTROESOPHAGEAL REFLUX IN PRETERM INFANTS & EFFECT OF PROKINETIC AGE Principal Investigator & Institution: Sinkin, Robert; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 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: GENETIC EPIDEMIOLOGY OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Romero, Yvonne; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 30-NOV-2005 Summary: Yvonne Romero's long term career goal is to decrease the mortality rate of esophageal adenocarcinoma. Yvonne is a Harvard undergraduate who completed a 3year Gastroenterology fellowship at Mayo in 1996, matriculated into the Clinical Epidemiology and Biostatistics Program at McMaster University in 1997, was the first Mayo Fellow in Diseases of the Esophagus in 1998, who joined the staff at Mayo in May 1999. Her clinical mentor, Alan J. Cameron, MD, is a recognized authority on Barrett's esophagus, a premalignant disorder. They have been addressing the question of familial gastroesophageal reflux disease and Barrett's esophagus since 1994. Their first project,

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Esophagitis

which showed aggregation of reflux symptoms in families of probands with Barrett's esophagus and esophageal adenocarcinoma (but not solo reflux esophagitis), was published in Gastroenterology in 1997. In the Barrett's Esophagus Genomic Study, for which Dr. Romero acts as primary investigator, 96 families with 3 or more effected persons have already been identified. A separate pilot study showed a trend of increased Barrett's esophagus prevalence among symptomatic relatives of probands with Barrett's compared to controls. Doctor Romero's immediate goals are to, 1) determine the risk of Barrett's esophagus and reflux esophagitis, the presumed precursor of Barrett's, among relatives of Barrett's probands compared to age-, sex-, medication- and symptom- matched controls without significant family history; and 2) collect blood from high- prevalence Barrett's esophagus families. Her intermediate goals are to 1) carry out a genome screen to map the chromosomal location of the gene(s) responsible for the phenotypes of reflux esophagitis and Barrett's esophagus using linkage analysis; 2) detect genetic heterogeneity as there is likely more than one major gene involved; and 3) fine map the genetic region(s) identified through linkage analysis, to identify the smallest genomic segment that contains the gene(s). To pursue this line of evidence in a scientifically stringent manner, Dr. Romero has been enrolled in genetic epidemiology coursework at the University of Minnesota since February 1999 and will continue to do so as supported by this award. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF SEVERE PEDIATRIC GASTROESOPHAGEAL REFLUX Principal Investigator & Institution: Ehrlich, Garth D.; Professor and Vice Chairman; Allegheny-Singer Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Adapted from investigator's abstract): Proposal to identify the gene responsible for autosomal dominant gastro-esophageal reflux. PI has already collected 8 families with autosomal dominant GER and mapped a gene within a 9 cM region on chromosome 13q14 (paper submitted). They are proposing to gather more families, narrow region, scan already existing ESTs in region for mutations, and identify new genes in high throughput genome sequence (htgs) database at NCBI. As they are doing this, they will also cover region in YAC and BAC contig and use genomic pull down (cDNA selection) to find genes expressed in a griddled gastroesophageal library they will construct from whole esophagus, including autonomic nerve trunks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: H. PYLORI AND IL-1BETA IN ESOPHAGEAL ONCOGENESIS Principal Investigator & Institution: Francois, Fritz; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): The reasons for the rise in esophageal adenocarcinoma in the last four decades are yet to be determined. H. pylori is the major risk factor for the development of peptic ulcer disease and gastric cancer, with the risk being higher with CagA + strains. The gastric inflammatory response to H. pylori may decrease acid production and reflux in the esophagus. Differences in the host mucosal inflammatory response to H. pylori have been attributed to IL-1beta polymorphisms. The study plan will investigate how polymorphisms in the IL-1beta locus might affect the risk for esophageal cancer development. The hypothesis is that by modulating the host inflammatory response to H. pylori and subsequent acid production, the IL-1beta-

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31*T allele and the functionally related IL-1RN allele decrease the risk of esophageal inflammation, metaplasia, and adenocarcinoma. To test this hypothesis, a prospective cross-sectional study of adult patients referred for ambulatory endoscopy will be performed. Demographic and clinical data will be obtained via questionnaire. Blood will be obtained from patients to measure lgG to whole cell H. pylori antigens as well as to CagA, and DNA will be extracted from isolated leukocytes for IL-1 genotyping. Biopsies will be taken from the stomach and distal esophagus, and patients will undergo 24-h pH monitoring after endoscopic evaluation to evaluate esophageal acid exposure. Biopsies will be used to culture H. pylori directly from the stomach, to identify the organism by histology, to assess the histologic status of the tissues, to measure IL-1 in the stomach and esophagus, and to measure Ki-67 and COX-2 expression in the esophagus. Specific aim #1 is to determine the effect of H. py/ori strain characteristics on gastric and esophageal mucosal IL-1beta protein expression, and on the development of the precursor lesions (inflammation, metaplasia, and dysplasia) to esophageal adenocarcinoma. Specific aim #2 is to determine the prevalence of the IL-1beta-31and IL-1RN alleles in relation to esophageal acid exposure, also in relation to H. pylori colonization. In particular, the effect of the IL-1beta-31and IL-1RN alleles on gastroesophageal junction (GEJ) cellular proliferation and cyclooxygenase-2 (COX-2) expression in patients with or without H. pylori colonization will be evaluated. Specific aim #3 is to evaluate the effect of H. pylori eradication on GEJ cellular proliferation, and on IL-1beta and COX-2 expression in relation to the IL-1beta-31 allele. From these studies, both the microbial contribution and the host genotype contribution to adenocarcinoma risk should be able to be assessed, as well as to begin to define relevant cellular pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFANTILE ESOPHAGITIS--NATURAL HISTORY AND OPTIMAL THERAPY Principal Investigator & Institution: Orenstein, Susan; Children's Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 152132583

Hosp

Timing: Fiscal Year 2002 Summary: To determine the optimal diagnostic strategy, and components and duration of therapy of infantile esophagitis. Both retrospective and prospective components. Infants will be randomized to therapy using a 2x2 factorial design using a prokinetic, an acid secretion inhibitor, both, or dual placebo. Patients will undergo repeat esophageal biopsies and reflux questionnaires to evaluate objective and subjective response to therapy and stability of healing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESOPHAGITIS

INFLAMMATION

AND

SIGNAL

TRANSDUCTION

IN

Principal Investigator & Institution: Biancani, Piero; Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 30-NOV-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESOPHAGUS

INOS,

COX-2,

AND

ARGINASE

IN

MURINE

BARRETT'S

Principal Investigator & Institution: Wilson, Keith T.; Associate Professor of Medicine; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Barrett's esophagus (BE) represents a substantial health care burden because it has a high frequency of progression to dysplasia and Barrett's-associated adenocarcinoma (BAA). A major reason for this problem is that we currently have limited approaches to prevent development of BAA, and of BE itself. If we could generate direct evidence that specific molecular pathways have a causative or preventive role in these events it would be of obvious benefit. Cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), the enzymes responsible for the high-output production of nitric oxide (NO) and prostaglandins, respectively, are both implicated in dysregulation of epithelial cell growth and in GI carcinogenesis. Recent evidence suggests that arginase, the endogenous competitive inhibitor of iNOS, has important biological effects by blocking NO synthesis, but also has direct effects via diversion of Larginine to other pathways, such as polyamine synthesis. Our data in human patients shows frequent and abundant expression of iNOS and COX-2 in BE and BAA, and we have recently determined that the arginase II enzyme (argll) is significantly downregulated in BE compared with the proximal esophagus in BE patients. We hypothesize that iNOS and COX-2 play a causal role in development of BE and in progression to BAA, while argll protects against these events. The PI proposes to use the R21 mechanism to apply his expertise about these enzymes in the GI mucosa to new studies in animal models of BE. In Aim 1, we will employ a surgical model of gastroduodenal-esophageal reflux created by esophagojejunostomy, which has been shown to produce BE in rats and has been recently applied to mice. We will develop this model in our lab and determine if COX-2 or iNOS deletion protects against, and if argll deletion enhances, development of BE and carcinoma. We will compare macroscopic and histologic evidence of BE and cancer, gene expression of COX-2, iNOS, and arginases, histologic evidence of apoptosis and proliferation in: A. wild-type (WT) vs. COX-2-/- mice, B. WT vs. iNOS-/- mice, and C. WT vs. argll-/-mice. In Aim 2, we will use injection of the lower esophageal sphicter (LES) with botulinum toxin (BoTx) to induce gastroesophageal reflux by inhibiting LES function. We will study macroscopic and histologic evidence of esophagitis, BE and BAA, gene expression, apoptosis and proliferation in A. wild-type (WT) vs. COX-2-/- mice, B. W'I- vs. iNOS -/-mice, and C. WT vs. argll -/- mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRAESOPHAGEAL PH & BILIRUBIN IN GERD ON GASTRIC ACID SUPPRESSION THERAPY Principal Investigator & Institution: Parkman, Henry P.; Associate Professor; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002 Summary: The objective of this study is to determine if acid or bile reflux into the esophagus is responsible for refractory symptoms of gastroesophageal reflux disease (GERD) despite gastric acid suppressant therapy, including histamine type-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI). This will be determined by simultaneously monitoring, over a 24 hour period, both esophageal pH and bilirubin

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concentrations in patients with GERD and to allow us to determine if acid reflux, bile refulux, both or neither is responsible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LANSOPRAZOLE EFFECTS IN PEDIATRIC ESOPHAGITIS Principal Investigator & Institution: Winter, Harland S.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 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: LANSOPRAZOLE IN PEDIATRIC PATIENTS W/ ESOPHAGITIS Principal Investigator & Institution: Heyman, Melvin B.; Professor of Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-DEC-2000; Project End 31-MAR-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MATRIX PARAMETERS AS MARKERS OF GASTROESOPHAGEAL INJURY IN CHILDREN Principal Investigator & Institution: Moustafellos, Elaine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002 Summary: The aim of this protocol is to study the role of zinc and its effect on collagen markers in the process of tissue repair in esophagitis and other forms of gastroesophageal injury in children. Additionally, we plan to see if serum biochemical markers may be used as a non-invasive method to monitor tissue repair and response to therapy in children with upper gastrointestinal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLEARANCE

MECHANISM

OF

GASTROESOPHAGEAL

REFLUX

AND

Principal Investigator & Institution: Massey, Benson T.; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002 Summary: The gastroesophageal junction is the first portal through which noxious gastric contents must pass if they are to cause injury to the upper aerodigestive tract. When reflux occurs excessively and clearance of reflux is impaired, patients can develop esophagitis, ulcers, stricture, adenocarcinoma, laryngitis, and aspiration pneumonia. Unfortunately, the mechanisms for initiating and suppressing reflux and the factors contributing to the altered clearance of the refluxate are poorly understood. The specific objectives of this subproject are to explore the following hypotheses: 1). Intragastric pressure is a major determination of whether reflux occurs, with reflux patients having lower threshold pressures for triggering reflux. 2). Afferent sensory pathways in the cardia of the stomach are important in triggering GERD. Agents can be delivered endoscopically to block these pathways and inhibit GER. 3). Esophageal longitudinal muscles play an active role in the reflux event. 4). Esophageal acidification alters the

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function of longitudinal esophageal muscles, so as to contribute to forming a hiatal hernia. 5). Longitudinal esophageal muscle function during primary and secondary peristalsis is abnormal in patients with reflux disease, and these abnormalities contribute to disturbances in esophageal bolus clearance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ESOPHAGEAL PAIN Principal Investigator & Institution: Sengupta, Jyoti N.; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2004; Project Start 15-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): Non-cardiac chest pain (NCCP) is a common functional esophageal disorder, with chronic unexplained symptoms without any identified structural disease. The pain is presumed to be of esophageal origin and is characterized by episodes of unexplained pain that are usually midline. The pain is easily confused with cardiac angina or pain from other esophageal disorders. About 15% - 30% of angiograms performed in chest pain patients are normal, and a coronary artery spasm rarely explains the symptoms. In United States, at least 500,000 coronary angiograms are performed annually for chest pain; NCCP may be present in 75,000 to 150,000. Physiologic mechanisms of underlying symptom production are poorly understood. Most of the available clinical information is from the patient that seeks treatment after the development of symptoms. Therefore, for most part the basic mechanisms that initiate the symptoms remain unknown. Often NCCP is associated with long history of acid reflux without development of esophagitis. It is thought that the hypersensitivity in NCCP could be due to sensitization of peripheral and/or central sensory neurons. The major goal of this research proposal is to understand peripheral sensory mechanisms of esophageal pain under normal physiological condition and during acute and chronic acidification of the esophagus. Electrophysiological and pharmacological studies will be undertaken to understand the roles of sensory neurons in pain and attenuation of their responses, respectively. The proposed specific aims involve systematic characterization of responses of vagal and spinal sensory afferent fibers to mechanical, thermal and chemical stimuli before and after acidification. The study will mainly focus to understand the contribution of cationic channels (ASICs, VR1/TRPV1 and CMR1), ionotropic glutamate receptors (NMDA and AMPA) and neurokinin receptors (NK1, NK2 and NK3) in neuroplastic changes of these neurons in acute and chronic acid exposure. The proposed work is a thorough investigation of peripheral mechanism of esophageal hypersensitivity and pain. The study will provide a valuable information about the adequate stimuli and response characteristics of the primary sensory afferent fibers and the manner in which their altered patterns contribute to visceral hyperalgesia and allodynia. Pharmacological study will provide insight in drug development in management of esophageal pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDICAL AND SURGICAL TREATMENT OF ESOPHAGEAL REFLUX Principal Investigator & Institution: Finlayson, Samuel R.; Surgery; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: Gastroesophageal reflux disease (GERD) is one of the most common disorders of the gastrointestinal tract. Approximately 75 million Americans suffer from

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"heartburn", the most typical symptom of GERD. Heartburn can severely impact quality of life and leads to an estimated 15 million physician consultations per year. Both medical and surgical treatments have been shown to be effective in controlling symptoms of GERD, but surgical intervention has traditionally been reserved for selected patients with intractable symptoms. However, for both medical and surgical treatment of GERD, the landscape has changed significantly in the last decade. Proton pump inhibitor therapy has proven vastly superior to older anti- acid medications. Concurrently, the advent of minimally invasive laparoscopic surgery as substantially lowered the threshold for surgical treatment of GERD and led to substantial increases in rates of anti-reflux surgery. Both of these advances have sharpened the debate surrounding optimal treatment of GERD, but at present there is insufficient evidence on which to base comparispon of medical and surgical treatment. A careful, prospective, multi-enter, randomized clinical trial would be the ideal mechanism for comparing proton pump inhibitor therapy and laparoscopic anti-reflux surgery for GERD. The purpose of this application is to seek funds to design and plan such a trial. As members of an experienced clinical trial consortium, we recognize that conducing this trial will require successfully overcoming several important challenges, including issues of patient recruitment and retention, generalizability, and measurement of quality-of-life outcomes. The R03 grant would provide the required financial resources to carefully address these challenges. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MII TO CHARACTERIZE REFLUX IN BARRETT'S ESOPHAGUS Principal Investigator & Institution: Castell, Donald O.; Chief; Medicine; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 30-APR-2006 Summary: (provided by applicant): This study will test the hypothesis that patients with Barrett's esophagus (BE) have a more severe defect in esophageal function and more gastroesophageal reflux (GER) compared to patients with uncomplicated GERD without BE and normal volunteers. This will be accomplished using a recently developed technology of multichannel intraluminal impedance (MII) as a more sensitive test of esophageal function and as a means of assessing GER of all types (acid and non-acid). Incorporating a special catheter, MII combined with intraluminal pressure transducers provides a more sensitive test of esophageal function, including the ability to measure bolus transit without radiation exposure. Likewise, a special catheter in which pH sensitive electrodes are combined with MII provides a sensitive technique to identify all forms of GER, independent of pH. We will prospectively study esophageal function and characteristics of GER in 20 patients with BE, 20 patients with uncomplicated GER (patient controls) and 20 healthy volunteers (normal controls). Following a baseline assessment, all participants will be treated with a proton pump inhibitor (esomeprazole 40mg) taken twice daily for a period of 8 weeks. Upon completion of 8 weeks of intensive therapy, each patient will have repeated studies of esophageal function while continuing on the acid suppressing regimen. These studies will identify whether acid suppression is as effective in patients with BE as in those with uncomplicated GERD and normal volunteers, including assessment of the level of intragastric acidity and evidence of persistent reflux, both the acid and non-acid component. It is anticipated that the studies outlined in this proposal will provide better clarification of the esophageal functional abnormalities occurring in patients with BE that permit a more aggressive form of gastroesophageal reflux disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Esophagitis

Project Title: MOLECULAR EPIDEMIOLOGY OF BARRETTS ESOPHAGUS AND CANCER Principal Investigator & Institution: Whiteman, David C.; Queensland Institute of Medical Research Herston Brisbane Qld, 4006 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The incidence of adenocarcinoma (AC) of the esophagus has increased rapidly in most countries during the past three decades, yet the reasons are not well understood. AC typically arises on a background of Barrett's esophagus (BE). At the population level, relatively little is known about the environmental and genetic causes of BE and AC, or about factors which modify the natural history of BE to cause progression to cancer. In this population-based study, we aim to quantify the risks associated with exposure to epidemiologic and genetic risk factors for reflux esophagitis (RE), BE and AC. In parallel biospecimen analyses, we aim to identify molecular subtypes of BE and AC using microarray gene expression profiling and tissue arrays. To accomplish these aims, we will sample representative groups of patients with biopsyproven RE [n=400], BE [n=700] or AC [n=300] from all pathology laboratories servicing the target populations during a 3 year period, and compare them with two groups of controls. A representative group of population controls [n=600] will be sampled from a compulsory electoral register, and a group of biopsynegative tissue controls [n=400] will be sampled from the pathology laboratories. Cases and controls will answer identical questionnaires, focusing on gastro-intestinal symptoms, exposure to medications (especially reflux promoters, NSAIDs, COX-2 inhibitors, hormones), as well as smoking, alcohol, infection with Helicobacter pylori and family history of cancer. Blood samples will be collected from participants to identify genotypes associated with predisposition to RE, BE and AC. From cases and tissue controls, we will obtain specimens of biopsy or surgical tissue with the aim of determining the prevalence of molecular subtypes of BE and AC. Fresh tissue will be available from a proportion of clinic-based AC cases [n=50-100] for gene discovery through microarray gene expression profiling. From comprehensive mining of the expression profiling data we will identify diagnostic markers for the different subtypes of BE and AC, prognostic markers that predict likelihood of progression and/or response to therapy, and targets for rational drug design to treat BE and AC. Candidate genes will be validated in the paraffin sections available for all cases and tissue controls using tissue array technology. Epidemiologic analyses will then be performed comparing risks of exposure among the major disease groupings (RE, BE, AC), as well as for the molecular subtypes of RE, BE and AC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUTRALIZATION AND ABSORPTION OF ASPIRATED FLUID IN LUNGS Principal Investigator & Institution: Effros, Richard M.; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002 Summary: This subproject is designed to evaluate the defense mechanisms in the lung that protect against aspirated gastric contents. The study will evaluate how the acid is neutralized by analyzing how the cystic fibrosis transmembrane conductance regulator (CRTCR) and other anionic and non-anionic epithelial transport processes are involved. The second major objective of this subproject is concerned with how the hypo-osmotic aspirate is reabsorbed from the airways, specifically, in regard to aquaporins in the

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epithelial and endothelial membranes. To evaluate these specific aims, a careful review of the airway transport processes was done and the preliminary studies presented in this application relative to the specific aims are very impressive. The studies on the transport processes responsible for neutralization will be conducted using perfused rat lungs and isolated human derived tracheobronchial and bronchiole epithelial cells and primary isolated rat epithelial cells. The questions posed are: Is buffering by anion transport specific, does neutralization occur by OH transport, is cystic fibrosis transmembrane conductance regulator (CFTR) involved, can acceleration of neutralization of the airway fluid be stimulated by increasing anion transport, does amelioride affect acid neutralization, is carbonic anhydrase involved in this process, what are the effects of the epithelial transport systems and aquaporins on edema fluid removal and finally, what occurs with alkaline solution? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NICOTINIC RECEPTORS IN NONNEURONAL CELLS AS TARGETS FOR NICTOINE TOXICITY Principal Investigator & Institution: Conti-Fine, Bianca M.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: Bronco epithelial cells, endothelial cells and esophagus keratinocytes express nicotinic acetylcholine receptors of neuronal type (nAChR) sensitive to nicotine (Nic): the overall goal of the proposed studies is to identify new mechanisms of Nic toxicity resulting from a direct effect on those nAChRs. Block of the nAChR in bronchial epithelial and endothelial cells causes cell paralysis and cell-cell detachment. Long term exposure to Nic causes nAChR desensitization, and will likely result in cell-cell detachment, leading to bronchitis and esophagitis, atherosclerotic lesions, and facilitated entrance of carcinogenic compounds. Acute exposure of bronchial epithelial cells to Nic causes apoptosis, that might be an additional mechanism of Nic toxicity. The proposed studies will have three major (1 to 3), and three minor (4-6) specific aims: 1) to investigate the structural and functional properties of nAChRs expressed by bronchial epithelial cells, endothelial cells and esophagus keratinocytes; to extend these studies to lung alveolar epithelial cells; by patch clamp and binding studies using ligands specific for different nAChR subtypes; by immunohistochemistry, using antibodies and protein probes specific for different nAChR subtypes; by PCR using subunit specific primers, followed by cloning and sequencing of the products; by in situ hybridization using subunit specific probes. 2) to demonstrate in these cells the presence of the enzymes that metabolize ACh; by immunohistochemical and to demonstrate in these cells the presence of the enzymes that metabolize ACh; by immunohistochemical and biochemical assays of the enzymes choline acetyltransferase and acetylcholinesterase. 3) to investigate the cellular functions modulated by Nic and ACh binding , and the effects of acute and chronic Nic exposure in vitro, using functional assays of cell adhesion, motility, and proliferation, and by measuring the rate of cell death and apoptosis after exposure to Nic. 4) to investigate the possibility that the nAChRs expressed by bronchial epithelial cells are a port of entry for rabies virus, explained rabies cases that result from airborne exposure. 5) to investigate the characteristics of the endothelia nAChRs expressed in patients with Buerger's disease, a vasculitis of the limb blood vessels caused or triggered by tobacco usage. 6) to do pilot investigations to test whether nAChRs are expressed at other non-neuronal locations involved in tobacco toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Esophagitis

Project Title: PILOT--BACTERIOCIDAL PERMEABILITY: INCREASING PROTEIN Principal Investigator & Institution: Furuta, Glenn T.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: Tissues lined by squamous epithelial cells are regularly exposed to a large number of infectious and non-infectious insults. As a result, the protective epithelium has evolved a series of innate defense mechanisms to maintain an equilibrium between normal tissue function and unwarranted tissue destruction. An exquisite example is the esophagus. The esophageal mucosa utilizes a number of protective mechanisms including peristalsis, mucous secretion, and bicarbonate exchange to minimize the influence of potential injurious agents. In addition, the healthy squamous epithelium contains a number of immunocytes including mast cells, lymphocytes and dendritic cells. Conversely, esophageal diseases also lead to significant morbidity including gastroesophageal reflux disease (GERD) and esophageal cancer, with a disease frequency of nearly 25 million U.S. citizens per year. A common marker for esophageal inflammation is the accumulation of eosinophils. Our recent studies have examined the influenced of eosinophil derived granule protein major basic protein (MBP) can significantly influence epithelial structure and function. It is not known whether eosinophils represent a "friend" or "foe" in esophageal inflammation. To begin to address this issue, we utilized gene chip analysis and determined that MBP markedly induced the synthesis of an innate molecule of defense, bactericidal permeabilityincreasing protein (BPI), a potent anti-infective molecule with microbial killing and endotoxin-neutralizing functions, with previous expression attributed only to leukocytes. Ongoing and endotoxin-neutralizing functions, with previous expression attributed only to leukocytes. Ongoing studies have: a) revealed that squamous epithelial express BPI, b) identified the BPI gene promoter and it's expression in squamous epithelia, and c) identified a murine homolog of BPI expressed in mucosal epithelia. From these preliminary data, we hypothesize that squamous epithelial BPI is central to esophageal responses to eosinophilic disease. Two specific aims are directed at testing this hypothesis. Specific Aim 1: Define molecular mechanisms of BPI expression in squamous epithelia. Preliminary data indicate that epithelial BPI is functionally relevant in bacterial killing and in control of endotoxin responses in epithelia. At present, essentially nothing is known about the factor(s) which regulate BPI expression. Ongoing studies have identified and characterized the BPI gene promoter, and here we propose to gain insight into how squamous epithelial BPI expression is regulated at the molecular level. Specifically, we will elucidate molecular determinants of BPI promoter constructs. Specific Aim 2: Characterize squamous epithelial expression of the BPI homolog in healthy and eosinophilic diseased murine tissue. Until recently, it was believed that mice did not express BPI. New data from the Mouse Genome Project identified a BPI homolog on chromosome 1, and our ongoing work has revealed that mouse epithelia express BPI. In these studies, we will extend these preliminary findings to profile squamous epithelial BPI expression in the esophagus, define expression of BPI in murine esophagitis animals, and examine BPI expression in human patient esophageal tissue. The long-term goal of this research is to elucidate the role of epithelial BPI in health and disease. A better understanding of these principles provide the potential for therapies aimed at ameliorating symptoms associated with mucosal infection and inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--MOUSE MODEL OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Cotsarelis, George; Assistant Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2007 Summary: Over the last two decades, the rate of increase in adenocarcinoma of the esophagus has exceeded that of any other carcinoma in the United States. Specialized columnar metaplasia of the intestinal type at the gastroesophageal junction or Barrett's esophagus, is recognized as a major risk factor for the development of dysplasia and adenocarcinoma of the esophagus. Injury of the esophageal squamous epithelium by acid reflux from the stomach or by H. pylori infection is thought to lead to the replacement of the squamous epithelium by glandular epithelium, followed by the appearance of intestinal-type goblet cells, which are not normally found in the stomach or esophagus. The specific cellular events leading to Barrett's esophagus, including the origin of the metaplastic cells (squamous vs. glandular) and the time course for the conversion to an intestinal phenotype are not well characterized. The overall goals of this proposal are to develop and utilize an inducible transgenic mouse model of Barrett's esophagus to study the pathogenesis of this disorder. We isolated the keratin 15 promoter that drives expression of transgenes to the squamous epithelium of the esophagus and forestomach in mice. By expressing the K15/HSV-1 thymidine kinase suicide gene using this promoter, we discovered that intestinal metaplasia that closely mimics Barret's esophagus develops at the squamocolumnar junction after administration of ganciclovir. In this proposal, we plan to: 1. further develop and molecularly validate this transgenic mouse model for Barrett's esophagus, 2. study changes in gene expression in the tissue at the squamocolumnar junction as it develops intestinal metaplasia following injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTECTION RADIOTHERAPY

OF

ESOPHAGUS/NORMAL

LUNG

FROM

Principal Investigator & Institution: Greenberger, Joel S.; Professor and Chairman; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: Irradiation-induced normal tissue damage is a major dose-limiting factor in the treatment of non-small cell lung carcinoma (NSCLC). Severe esophagitis of Grade 3 or 4 occurs in approximately 30% of patients during their over 25% of surviving patients by significant irradiation fibrosis occurring 6 months-2 years after RT. These irradiationinduced effects are exacerbated by chemotherapy. Prevention of normal tissue damage may allow for increased doses of chemotherapy and irradiation thus increasing both clinical response and survival in NSCLC. We have demonstrated significant reduction in inflammatory cytokine response, esophagitis, organizing alveolitis (fibrosis), and radiosensitization of orthotopic Lewis lung (3LL) carcinoma tumors with increased survival in a mouse model by manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) complex injections 24 hours prior to irradiation. Project #4 of the UPCI Lung Cancer SPORE proposes to demonstrate in clinical trials that over-expression of MnSOD in normal tissue projects chemoradiotherapy (CRT)-induced damage. In the first specific aim, we will demonstrate in clinical trial biweekly MnSOD-PL administration to the esophagus will result in decreased esophagitis in lung cancer patients undergoing CRT. The optimal biological effective dose, safety of MnSOD-PL, and prevention of esophagitis will be evaluated. In the second specific aim, the

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Esophagitis

effectiveness of a known lung radioprotective protocol of intratracheal (IT) administered MnSOD-PL in radiosensitization of orthotopic 3LL tumors will be optimized in a mouse model. In the third specific aim, a clinical trial will evaluate the use of inhalation of freedried MnSOD-PL in radiosensitizing primary NSCLC tumors during CRT. Parameters to be studied include optimizing the biological effective dose, safety of intraesophageal (swallowed), and inhalation MnSOD-PL administration, and effectiveness of normal tissue protection during radiosensitization of tumors. Methods include clinical trials management, histopathology, esophagoscope and biopsy, bronchoalveolar lavage (BAL), cytokine level measurements, nested RT- PCR, and biochemistry. These studies should lead to both an improved quality of life and potential for dose escalation in lung cancer patients requiring CRT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTIFYING EFFECTS OF TREATMENT OF PEDIATRIC DYSPHONIA Principal Investigator & Institution: Mcmurray, James Scott.; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2006 Summary: (provided by applicant): The diagnosis and management of childhood dysphonia is a significant clinical problem; however, there have been few studies aimed at defining standard assessment methods for pediatric dysphonia. Accordingly, pediatric dysphonia is difficult to diagnose and it is difficult to quantify change following treatment. The long-term goal of this research program is to develop valid, responsive, reliable, and age-appropriate methods for assessing vocal pathology in children. In the present small grant, our objective is to define assessment methods that are appropriate for use in determining response to treatment. Our main focus, therefore, is the issue of assessment responsivity. The first specific aim is to develop a set of responsive measures of vocal pathology in school-aged children by inducing short-term change in vocal status via behavioral and medical management of extraesophageal reflux disease (EERD). Because we are treating children suspected of EERD, this study also presents the opportunity for examining the benefits of combined vocal hygiene and medical management in the treatment of pediatric EERD. Accordingly, our second specific aim is to determine predictive criteria for improvement in vocal status in dysphonic children suspected of EERD. Our hypothesis is that a particular set of measurements will emerge as particularly responsive to change in vocal pathology in this population, and will allow for informed prediction of degree of improvement with treatment. The proposed research is significant in filling a gap in knowledge in childhood dysphonia assessment and treatment, which are important clinical issues consistent with the mission and intent of the NIDCD. Because phonatory disorders in children may have lasting negative effects, studies geared toward accurate assessment and treatment are very important. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REDEFINITION OF GASTROESOPHAGEAL REFLUX IN CHILDREN Principal Investigator & Institution: Mousa, Hayat; Children's Research Institute 700 Children's Dr Columbus, Oh 432052664 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): The prolonged measurement of the pH values close to the lower esophageal sphincter (LES) is considered the "gold standard" in the

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diagnosis of gastroesophageal reflux (GER). A pH below 4.0 is considered indicative of GER. Conventional pH measurement detects only acidic GER, it can not detect a refluxate in the intermediate pH range (pH 4 -7.0) due to the proximity to normal esophageal pH (5-6.8), nor can it detect episodes of reflux during or after meals. Consequently a major amount of reflux episodes are concealed from pH monitoring. A recently developed procedure for the recording of gastrointestinal motility by means of multiple intraluminal impedance measurement (MII) is based on the registration of changes in the impedance during the passage of a bolus. Since food, saliva and gastric fluid are better electrical conductors than the muscular wall of the esophagus, a significant and specific change in impedance traces can be observed for each propulsive or retrograde flow. We propose using this new technology in a study of GER in pediatric patients with apnea. Newborn to 2-year-old children who were admitted to Columbus Children Hospital with apnea and referred for a pH probe will be eligible for participation. After consent, pneumogram leads will be connected to patients, and dual pH and impedance catheter will be placed via the nares into the distal esophagus. Placement will be verified by fluoroscopy. The pneumogram and impedance will be monitored simultaneously. The number, time duration, height, and pH of each reflux episode will be evaluated and correlated to the presence of apnea. We will compare the disease predictive ability between pH-metry and impedance method. We hypothesize that a significant proportion of GER is missed using the current pH dependent method. This study will improve current diagnostic approach, increase life expectancy and improve quality of life in children who suffer from apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REFLUX SIGNS/SYMPTOMS

DISEASE

IN

PATIENTS

WITH

THROAT

Principal Investigator & Institution: Vaezi, Michael F.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 30-JUN-2005 Summary: (provided by applicant): This application is designed to provide Michael F. Vaezi, M.D., Ph.D., with a program of mentored, patient-oriented research that will facilitate his development as an independent physician scientist. This proposal outlines a series of studies designed to address the study hypothesis: there is a causal relationship between gastroesophageal reflux disease (GERD) and laryngeal symptoms and signs in patients with laryngitis. This award will allow Dr. Vaezi the unique opportunity to acquire cross-training in clinical design, epidemiology and biostatistics while pursuing a multidisciplinary, patient-oriented research project in better understanding an important clinical area. Laryngoscopic examination of patients with symptoms of hoarseness, sore throat, throat clearing and chronic cough commonly shows laryngeal abnormalities including laryngitis and vocal cord lesions including polyps, granuloma and carcinoma. Gastroesophageal reflux disease often is proposed as the etiology of these abnormalities. However, aggressive acid suppression improves symptoms and laryngeal findings in only some of these patients, highlighting the uncertainty of the relationship between acid reflux and laryngeal pathology. Furthermore, the pathophysiologic role of non-acidic gastric contents in the those whose acid reflux is suppressed with medication is unknown. The advent of new technologic advancement in the field of monitoring acidic and non-acidic reflux in an ambulatory setting will allow Dr. Vaezi to better understand the role of these potential gastric refluxates in causing laryngeal symptoms and injury. Therefore, to better understand the relationship between GERD and laryngeal injury, we propose three in-depth

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research protocols addressing the following aims: Aim #1: Identify specific laryngoscopic signs associated with GERD. Specific laryngeal signs of gastroesophageal reflux disease will be determined by identifying the signs found in normal subjects and comparing these subjects to reflux patients whose signs improve or resolve with acidsuppressive therapy. In 100 subjects with suspected acid-related laryngeal pathology, the response to aggressive acid suppression with proton pump inhibitors with and without H2-receptor antagonists will be tested with special interest in identifying potential predictors of response, optimum acid-suppressive regimen, dosing and duration of therapy. Aim #2: Identify potential pre-therapy predictors of successful response to GERD related ENT abnormalities. There are currently no data on predictors of response in this group of patients. A major reason for this has been the lack of a large scale trial in which different physiologic tests are performed prior to treatment. In this proposal, in addition to identifying demographic features, we will also perform esophageal manometry, esophageal and hypopharyngeal pH monitoring and multichannel intraluminal impedance (MII) pre- and post-therapy in order to identify potential predictors of successful response. Aim #3: Clarify the role of acidic and nonacidic esophageal reflux in causing laryngeal mucosal injury in patients with ENT complaints. This will be achieved using the state-of-the-art techniques of ambulatory multichannel intraluminal esophageal impedance and pH monitoring. These methods will be employed pre- and post-therapy on all patients to assess their potential clinical utility, especially in those unresponsive to medical therapy after aggressive acid suppression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ACID IN THE DEVELOPMENT OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Souza, Rhonda F.; Assistant Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Gastroesophageal reflux disease (GERD) has been established as a strong risk factor for esophageal adenocarcinoma. GERD can be complicated by esophagitis, and by replacement of esophageal squamous mucosa with the metaplastic mucosa of Barrett's esophagus (BE). In the setting of continued peptic injury, BE can give rise to esophageal adenocarcinoma. It is not known why only a minority of individuals with GERD develop BE, or why only a minority of individuals with BE develop esophageal adenocarcinoma. One reason for this void is that the molecular events triggered by acid reflux which mediate the development and neoplastic progression of BE are poorly characterized. Preliminary data from our laboratory demonstrate that acid activates the mitogen activated protein kinase (MAPK) pathways in the metaplastic mucosa of patients with BE, and in the squamous mucosa of normal subjects and of patients with GERD who do not develop BE. In contrast, we found that acid fails to activate the MAPK pathways in the squamous mucosa of patients with BE. We hypothesize that acid activates the MAPK-dependent signal transduction pathways which increase expression of cyclin D1, and trigger an increase in cell proliferation and a decrease in apoptosis in normal esophageal squamous epithelium and in the metaplastic epithelium of BE. Based on our preliminary data, this basic hypothesis has clinical implications for both the development and neoplastic progression of BE. In the esophageal squamous epithelium from normal patients and patients who do not develop BE, acid activation of MAPK-dependent pathways may promote repair of the acid damaged esophageal mucosa; in patients who develop BE,

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failure of acid to activate MAPK pathways may prevent regeneration of the acid damaged squamous mucosa and predispose to repair through metaplasia. However, once BE develops, acid stimulation of MAPK-dependent pathways may predispose to the development of esophageal adenocarcinoma. The aims of our study are to evaluate the acid induced effects on the ERK, p38, and JNK MAP kinase pathways, the AP-1 family of transcription factors, cyclin D1 expression, and its effect on cell proliferation and apoptosis in Barrett's metaplasia and esophageal squamous mucosa using in vivo and in vitro systems. Our long term goals are to identify molecular markers of BE and molecular targets at which to direct chemopreventive and chemotheapeutic agents for patients with BE and esophageal adenocarcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE ADENOCARCINOMA

OF

H.

PYLORI

INFECTION

IN

ESOPHAGEAL

Principal Investigator & Institution: Tchou-Wong, Kam-Meng M.; Assistant Professor; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining. The decreasing prevalence of cagA+ Helicobacter pylori may be associated with the rising incidence of esophageal adenocarinomas in industrialized countries. Colonization with cagA+ strains has been shown to be inversely associated with reflux esophagitis and Barrett's esophagus. A lower prevalence of cagA+ Helicobacter pylori has been observed in patient with gastroesophageal reflux disease (GERD) which results from acid exposure to the esophagus. One explanation for the negative association between colonization with Helicobacter pylori and GERD is the effect of Helicobacter pylori on acid production. Eradication of Helicobacter pylori has led to the development of GERD in a proportion of treated patients. These clinical evidence has led to the hypothesis that Helicobacter pylori could play a protective role in the development of GERD, especially reflux esophagitis. Experiments proposed in the following specific aims will test the hypothesis that Helicobacter pylori, especially the cagA+ strains, may protect against GERD, Barrett's esophagus and esophageal adenocarcinoma. The specific aims are as follows: 1. To study the effects of gastric colonization of cagA+ and cagA- strains of Helicobacter pylori on host inflammatory responses in rats and mice. 2. To determine the effects of Helicobacter pylori infection in reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in rats. 3. To determine the effects of Helicobacter pylori infection in esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in wild-type and p53 knockout mice. The proposed studies aim to ascertain the role of Helicobacter pylori colonization in the development of reflux esophagitis, Barrett's esophagus and its associated adenocarcinoma in rodent models. This proposal utilizes the innovative surgical models of GERD, BE and EAC for studying the protective role of Helicobacter pylori against reflux complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL TRANSDUCTION IN PROGRESSION OF BARRETTS ESOPHAGUS Principal Investigator & Institution: Cao, Weibiao; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923

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Esophagitis

Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): SPECIFIC AIM: 1. Determine the production of proinflammatory cytokines, H202 and prostaglandin E2 in the mucosa of patients with BE. 2. Analyze the effect of PPI treatment on the production of cytokines, PGE2 and H202 and the progression from metaplasia to dysplasia. 3. Determine the effects of acid exposure on cytokines, PGE2 and H202 production in esophogeal mucosa of BE patients. 4. Determine signaling pathways involved in the upregulation of COX-2 following acid exposure. 5. Determine whether IL-lb induces production of IL-6. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE AND FUNCTION OF HUMAN SALIVARY MUCINS Principal Investigator & Institution: Troxler, Robert F.; Professor; Biochemistry; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: Salivary secretions contain two distinct mucins, a high molecular weight mucin named MG1 and a low molecular weight mucin named MG2. Mucins protect oral surfaces against desiccation, form a selectively permeable diffusion barrier between underlying surfaces and the external environment, lubricate hard and soft tissues to minimize mechanical injury, facilitate speech and swallowing and provide a physical barrier to protect against colonization of potentially harmful microbes and viruses. We have shown that MG1 is actually a mixture of mucin gene products, containing MUC4, MUC5B and a novel salivary mucin (NSM), whereas MG2 is a single gene product encoded in the MUC7 gene. MG1 and MG2 are differentially expressed in major and minor salivary glands and the overall goal of this project is to understand their structural features and functional properties. The specific aims of this project are to: 1. determine the structural organization and sequence of mucin gene products comprising MG1 by characterization of a novel salivary mucin (NSM) and elucidating the Cterminal sequence of MUC4. 2. investigate the biosynthesis and assembly of MUC4, MUC5B and NSM using mucin constructs expressed in COS-7 cells. 3. evaluate interactions of MG2 with oral microbes and investigate MG2 heterotypic complexes with other salivary proteins in the yeast two hybrid system. 4. study expression of trefoil peptides in major and minor salivary glands using immunohistochemistry and in situ hybridization. 5. examine MG1 and MG2 levels in salivary secretions and whole saliva and determine secretion profiles using mucin-specific capture ELISAs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES OF ESOPHAGEAL METAPLASIA USING A NOVEL ANTIBODY Principal Investigator & Institution: Das, Kiron M.; Professor; Medicine; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The overall hypothesis for this proposal is that metaplastic epithelium at the distal esophagus is an intestinal metaplasia of colonic phenotype, and the process may lead to specialized columnar epithelium (SCE), or Barrett's epithelium (BE), due to various environmental factors. We developed a novel monoclonal antibody (mAb) 7E12H12 IgM isotype, also known as mAb Das-1, that specifically reacts with normal colon epithelium, but not with any other parts of the gastrointestinal tract. However, we reported that it reacts with SCE and adenocarcinoma

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arising from SCE with 100% specificity. Preliminary studies also demonstrate that "cardiac type" of epithelium at the esophago-gastric (E-G) junction reacts with mAb Das1. Using biopsy specimens from E-G junction and mAb Das-1, by immunoperoxidase assay (IPA), we will determine the frequency of intestinal metaplasia at the distal esophagus (IM-DE) reactive to mAb Das-1 without histological evidence of SCE. The relationship of IM-DE to history of gastroesophageal reflux disorder, age, sex and ethnic background and use of anti-secretory drugs, such as H2-blockers and proton pump inhibitors (PPI) will be evaluated. We will further examine if patients with IM-DE eventually develop SCE over 2 to 4 years of follow-up studies. Reversibility of this metaplastic process will be examined by early "chemoprevention" using PPI in patients who display IM-DE without histological evidence of SCE. To investigate if mAb Das-1 is a better predictor than histology, the presence of the immunoreactivity and parallel histology will be utilized to monitor eradication and recurrence of BE following ablative therapies. Colon epithelial protein-epitope (CEP), recognized by mAb Das-1 will be ultrastructurally localized by immunoelectronmicroscopy and confocal microscopy. Biochemical and molecular studies will utilize characterization of CEP, change in the expression of CEP following exposure of BE cell lines to various environmental factors such as acid pH, and proinflammatory cytokines and cloning of CEP gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE EPIDEMIOLOGY OF BARRETT'S ESOPHAGUS IN CHILDREN Principal Investigator & Institution: Gilger, Mark A.; Associate Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 31-JUL-2006 Summary: (provided by applicant): Barrett's Esophagus (BE) is the only known precursor lesion for esophageal adenocarcinoma, which is the fastest rising cancer in Caucasian men in the United States. The age of onset of BE is unknown. BE results from chronic gastroesophageal reflux disease (GERD), which is known to develop during childhood. Hence, childhood GERD could be a risk factor for BE. The goal of the proposed research is to examine the epidemiology of BE in children and adolescents using retrospective as well as prospective data collected in the multicenter network project known as Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative (PEDS-CORI). The Specific Aims are (1) to determine the prevalence of BE as defined by endoscopic and histologic criteria in children and adolescents undergoing upper endoscopy; and (2) to evaluate the demographic features (age, gender, ethnicity) and clinical determinants (comorbidity, GERD symptoms) of BE as defined by uniform endoscopic and histologic criteria among children and adolescents undergoing endoscopy. These aims will be achieved through two cross-sectional studies designed to obtain estimates of the prevalence of BE: a retrospective study using information collected from all PEDS-CORI sites between 1999 and 2004 (an expected 16,000 procedures), followed by a one-year prospective endoscopic study in three PEDS-CORI sites (an expected 1,800 procedures), in which additional BE-specific information will be collected. The prospective study includes rigorous standardization of the observation and recording of endoscopic and histologic findings and specific questions about potential risk factors. The long-term objectives of this research are to lay the groundwork in terms of feasibility and sample size for a prospective multicenter study involving all PEDS-CORI sites that will examine the risk factors for BE in children and adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ESOPHAGOGASTRIC JUNCTION IN HEALTH AND DISEASE Principal Investigator & Institution: Kahrilas, Peter J.; Professor of Medicine; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Verbatim from Applicant's Abstract): Gastroesophageal reflux disease (GERD) is a common disorder, affecting millions of Americans and caused by anatomical and physiological perturbations of the esophagogastric junction (EGJ). The economic impact of GERD in the US is evident by the annual expenditure of >$4 billion for pharmaceutical treatments. Although effective, medical therapy is by nature compensatory, as opposed to potentially curative surgery. However, a problem with antireflux surgery has been unpredictable postoperative dysphagia and bloating related to a diminished ability to belch. Thus, this revised RO1 application represents a collaborative effort by a gastroenterologist (Dr Kahrilas), a surgeon (Dr Joehl), and a mechanical engineer (Dr Brasseur) to study perturbations of the EGJ imposed by GERD and by surgical treatments of GERD (Nissen fundoplication). Specific aim #1 addresses antegrade EGJ function while specific aim #2 investigates mechanisms of reflux. Antegrade EGJ function will be quantified with an "esophageal stress test" using manometry with concurrent fluoroscopy while swallowing boluses of defined viscoelastic properties. These data will be complimented by a dysphagia questionnaire. Data from controls will be compared to that of GERD patients and patients after antireflux surgery. The underlying hypothesis of specific aim #1 is that a mathematical model of the EGJ, embedded within a "computer laboratory" and based on the best anatomical and physiological data obtainable will improve understanding and prevention of post-surgical dysphagia. Specific aim #2 is focused aboutextending our investigations into the interplay between anatomical and physiological factors in the pathophysiology of GERD. Investigational methodologies include using a barostat to create measured degrees of gastric distension and to ascertain EGJ compliance during fluoroscopy of the EGJ, using intragastric air insufflation to study the physiology of transient LES relaxations and high resolution manometry to map the geometry and mobility of the EGJ. An underlying hypothesis is that the optimal surgical management of a patient with tLESR induced reflux is different than of the patient with a patulous sphincter. The ultimate goal is to tailor the surgical management of GERD for the individual patient based on physiological studies of that patient with the hope that this will improve the efficacy and reduce the complications of antireflux surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE HIGH PRESSURE ZONE OF THE DISTAL ESOPHAGUS Principal Investigator & Institution: Miller, Larry S.; Medicine; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: (Applicant's Abstract): The PI's hypothesis is that the crural diaphragm interacts with the intrinsic lower esophageal sphincter in a very complex manner. These interactions take two forms: 1) space-time interactions in which the crural diaphragm and intrinsic lower esophageal sphincter (LES) are displaced from each other both in space and in time; and 2) mechanical interactions in which each component of the LES and CD contributes to the pressure generated at the gastroesophageal junction highpressure zone (GEJHPZ) individually and in combination. When there are abnormalities in either of these interactions, at the GEJHPZ reflux events and retrograde flow of fluids will occur. The purpose of this proposal is to determine the relative physiologic roles of

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the intrinsic LES and CD in providing an anti-reflux barrier at the GEJHPZ. The PI plans to define the relative motion of the CD to the intrinsic LES the relaxation and contraction of the CD in relationship to the LES, the compressive effect and forces of the CD on the distal esophagus, the role of the CD in antegrade movement of liquids and the role of the CD in induced relaxation of the GEJHPZ and retrograde movement of liquids from the stomach to the esophagus. Simultaneous high-resolution ultrasound and manometry will be utilized to correlate anatomical position (structure) with pressure (function). To achieve these specific aims the PI plans to: 1) determine the effect of respiration on the position and pressure relationships of the intrinsic LES and CD as components of the GEJHPZ. The investigators hypothesize that respiration causes movement of the crural diaphragm relative to the intrinsic LES and, therefore, effects the anatomical relationship of these two structures to each other; 2) separate the intrinsic LES from the crural diaphragm using physiologic and pharmacologic manipulations. The manometric contribution of the CD to the GEJHPZ will be determined by using pharmacologic and physiologic maneuvers to strengthen, diminish and even ablate the effects of the CD in order to better define the contribution of the CD to the GEJHPZ: 3) determine the effect of esophageal shortening during swallowing on the antireflux barrier GEJHPZ. This will be done by quantitating, the relative displacement of the intrinsic LES and CD to each other, in response to esophageal shortening, during swallowing of various bolus volumes of water; and 4) utilize several conditions in which the CEJHPZ structure and function are distorted to study the relative roles of the LES and CD. These conditions include hiatal hernia (displacement of the LES); Nissen fundoplication (reinforced HPZ) prior resection of the gastroesophageal junction (loss of the intrinsic LES); and GERD with and without hypotensive LES. Aim 5 Study the effect of retrograde flow at the GEJHPZ by inducing relaxation of the GEJHPZ and eliciting reflux events. This will be achieved by distending the fluid filled stomach with an air filled balloon, or distending the esophagus with an air filled balloon to induce relaxation of the GEJHPZ and elicit retrograde fluid movement from the stomach to the esophagus in normal controls and patients with GERD with and without a hypotensive LES. They will delineate both the normal and abnormal interactions of the LES and CD, using simultaneous ultrasound and manometry to define the physiology and pathophysiology of the GEJHPZ. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE PREVALENCE OF BARRETT'S ESOPHAGUS IN PATIENTS WITH * Principal Investigator & Institution: Jobe, Blair A.; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The incidence of esophageal adenocarcinoma arising from Barrett's metaplasia has increased by 350% since 1970 and at the time of presentation, 50% of patients will have advanced disease with virtually no chance for cure. The prognosis for esophageal adenocarcinoma arising from Barrett's metaplasia is poor: The overall 5-year survival rate is less than 10%. Patients with classic and chronic symptoms of gastroesophageal reflux disease (GERD) undergo endoscopic screening for Barrett's metaplasia. Several retrospective studies have demonstrated an earlier stage of diagnosis and a marked improvement in survival of patients with cancers detected by routine endoscopic surveillance for Barrett's esophagus. In spite of these efforts, the majority of patients who develop esophageal adenocarcinoma are unaware of the presence of Barrett's metaplasia prior to cancer diagnosis. In addition, a large proportion of these patients have never reported symptoms of GERD. These findings suggest that

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the majority of patients who are at highest risk for the development of esophageal adenocarcinoma are never screened for Barrett's metaplasia. Some investigators have suggested that patients who develop esophageal cancer may not have typical GERD symptoms and therefore are not identified for endoscopic screening. As a result, occult disease progression occurs and advanced cancer is present at the time of diagnosis. Substantial published data support a causal relation between complicated GERD (esophagitis and Barrett's metaplasia) and extraesophageal reflux symptoms. The prevalence of GERD-related esophageal injury in patients with isolated extraesophageal symptoms (i.e., no heartburn or regurgitation) is unknown. The primary aim of this study is to establish that patients with symptoms of extraesophageal reflux who are referred to an otolaryngology clinic have a prevalence of Barrett's metaplasia equivalent to that of a population with GERD symptoms. We will compare the prevalence of biopsy proven Barrett's metaplasia in patients with extraesophageal reflux symptoms with patients who have GERD symptoms and those who do not have GERD symptoms. The two comparison groups will be prospectively accrued through the Clinical Outcomes Research Initiative (CORI) endoscopic database at Oregon Health and Science University and the Portland VA Medical Center. This pilot study will provide needed data to improve risk stratification for esophageal adenocarcinoma and potentially modify the inclusion criteria for routine Barrett's screening. In addition, this study will enhance our understanding of the natural history of esophageal injury in patients with extraesophageal reflux and raise awareness of non-GERD risk factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UGI HEMORRHAGE AND BARRETT'S EPITHELIUM Principal Investigator & Institution: Jensen, Dennis M.; Professor of Medicine; Ctr for Ulcer Research & Educ; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 01-JUL-1999; Project End 30-JUN-2009 Summary: (provided by applicant): My primary career goals related to this award are: 1) to pursue a program of investigator-initiated, hypothesis driven, high quality patientoriented research in the specialty of digestive diseases, 2) to mentor young clinicians, with little or no research experience, in their career development as patient-oriented researchers, 3) to continue to mentor and collaborate with other clinical researchers who are beyond the entry level as clinical investigators, and 4) to contribute to career development of GI fellows who are funded on an NIH GI Training Grant. Three research studies support this research and mentoring proposal. These are collaborative research studies currently funded by this K24, the CURE Core Grant, and industry (for PPI's). The first is "Secondary Prevention of Barrett's Epithelium: Pathogenesis, Risk Factors, and Outcomes of Medical or Surgical Therapy". The principle hypothesis is that medical therapy will be more efficacious and cost effective than laparoscopic fundoplication as secondary prevention in recurrence of Barrett's epithelium. The second is "Development of Risk Scoring Instruments to Predict Outcomes and Probable Bleeding Sites in Patients with Severe Hematochezia". The primary hypothesis is that a scoring system developed from analysis of large CURE databases of patients with severe hematochezia and based upon clinical variables on presentation can predict outcomes (such as rebleeding and need for endoscopic hemostasis or surgery), and help identify the subgroup of patients most likely to benefit from urgent, sedated colonoscopy. This prospective data collection was funded by recently completed NIH grants. The third study is a feasibility study entitled "Prophylactic Banding or Propranolol to Prevent First Variceal Hemorrhage". The principle hypothesis is that initial failure of medical therapy

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(as monitored clinically and by hepatic venous pressure gradient) will be significantly higher and less cost effective than band ligation of varices (as monitored clinically and by endoscopy) in reducing the potential risk of first variceal hemorrhage. The mentoring of young investigators is now through structured masters degree programs and features didactic courses in biostatistics, seminars in study design, and other instruction in data management, form design for prospective trials, and protocol writing. Mentoring emphasis will be placed on planning, designing, and conducting actual prospective randomized studies. This award will continue to enhance the applicant's research productivity and provide skilled mentoring for young investigators, so they can become independent patient-oriented investigators in digestive diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VAGAL GASTRIC MOTOR CONTROL IN MICE Principal Investigator & Institution: Partoseoedarso, Elita R.; Pharmacology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2004 Summary: (Adapted from the Applicant's Abstract): Impairment of gastric adaptive relaxation reflexes is an underlying cause of gastroparesis. It may also contribute to gastroesphageal reflux disease and metaplasia (Barretts). In the hindbrain, vagal motor output to the gastric fundus is from preganglionic cholinergic neurons that are both excitatory and inhibitory. The inhibitory pathway is termed non-adrenergic noncholinergic (NANC) and evokes relaxation of the stomach via enteric nitric oxide (NO) and vasoactive polypeptide inhibitory motor neurons. To manipulate this pathway we currently use pharmacological and molecular antisense techniques in rats. However, it is clear that the most powerful molecular tools are in mice with targeted genetic mutations. Therefore, in this exploratory proposal we will modify our physiological recordings and stereotaxic brain microinjections for use in mice. This would be a unique approach in the field of brain-gut interactions. In rats, we (and others) have successfully measured gastric relaxation by intragastric balloon pressure. However, the extent of gastric relaxation is limited by the inherent compliance of the intragastric balloon and the initial imparting pressure. This can be circumvented by use of a barostat, which measures changes in intragastric volume using an open system in large animals and human. Barostats have recently been miniaturized for rodents. The first hypothesis is that gastric relaxation is evoked by GABAb and NK1 receptors in neurons of the dorsal motor nucleus of the vagus (DMN) of mice. Mice will receive mid-collicular decerebration to circumvent potentially confounding effects of anesthesia and low baseline gastric tone. NO mediates gastric relaxation at many sites in the brain-gut 'highway'. Specifically, gastric relaxation is regulated by hindbrain NO input into the dorsal vagal complex, by preganglionic NO containing vagal neurons and by inhibitory motor neurons at the neuromuscular junction. The second hypothesis is that cholinergic tone withdrawal is retained in centrally evoked gastric relaxation in NO synthase knockout mice. We predict that the extent of gastric relaxation is impaired compared to control mice. This proposal will enable us to surmount the difficulties associated with physiological miniaturization. Thus we will be able to exploit genetically engineered mice using state-of-the-art equipment for measuring intragastric volume. This will be critical for understanding how the underlying genetic components translate into alterations in neural control of gastric motor function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.3 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with esophagitis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “esophagitis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for esophagitis (hyperlinks lead to article summaries): •

A novel endoscopic appearance of idiopathic eosinophilic esophagitis. Author(s): Ahmed A, Matsui S, Soetikno R. Source: Endoscopy. 2000 June; 32(6): S33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10863926

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A placebo-controlled dose-ranging study of lansoprazole in the management of reflux esophagitis. Author(s): Earnest DL, Dorsch E, Jones J, Jennings DE, Greski-Rose PA. Source: The American Journal of Gastroenterology. 1998 February; 93(2): 238-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9468251

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A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Author(s): Villanueva A, Arathoon EG, Gotuzzo E, Berman RS, DiNubile MJ, Sable CA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 November 1; 33(9): 1529-35. Epub 2001 October 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588698

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A review of the clinical and economic impact of using esomeprazole or lansoprazole for the treatment of erosive esophagitis. Author(s): Raghunath AS, Green JR, Edwards SJ. Source: Clinical Therapeutics. 2003 July; 25(7): 2088-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946553

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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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Achalasia with Candida esophagitis during pregnancy. Author(s): Kalish RB, Garry D, Figueroa R. Source: Obstetrics and Gynecology. 1999 November; 94(5 Pt 2): 850. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546761

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Acid reflux is a poor predictor for severity of erosive reflux esophagitis. Author(s): Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2565-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452396

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Acute necrotizing esophagitis. Author(s): de la Serna-Higuera C, Martinez J, Martin-Arribas MI, Rodriquez-Gomez S, Perez-Villoria A, Betancourt A. Source: Gastrointestinal Endoscopy. 2001 August; 54(2): 225. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474395

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Acute necrotizing esophagitis: a case report. Author(s): Odelowo OO, Hassan M, Nidiry JJ, Marshalleck JJ. Source: Journal of the National Medical Association. 2002 August; 94(8): 735-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12152932

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Administration of H2 receptor antagonist with proton pump inhibitor is effective for long-term control of refractory reflux esophagitis. Author(s): Adachi K, Komazawa Y, Mihara T, Fujishiro H, Ishihara S, Amano Y, Kinoshita Y. Source: Journal of Clinical Gastroenterology. 2004 March; 38(3): 297-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128081

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Alendronate-associated esophagitis: endoscopic and pathologic features. Author(s): Ribeiro A, DeVault KR, Wolfe JT 3rd, Stark ME. Source: Gastrointestinal Endoscopy. 1998 June; 47(6): 525-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647380

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Alkali esophagitis and sucralfate. Author(s): Ehrenpreis ED. Source: The American Journal of Gastroenterology. 1988 October; 83(10): 1187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3421232

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Alkaline esophagitis evaluated by endoscopic ultrasound. Author(s): Kamijo Y, Kondo I, Soma K, Imaizumi H, Ohwada T. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(6): 623-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762671

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Alkaline reflux esophagitis. Author(s): Bushkin FL, Woodward ER. Source: Major Probl Clin Surg. 1976; 20: 64-71. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=957784

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Allergic esophagitis in children: a clinicopathological entity. Author(s): Walsh SV, Antonioli DA, Goldman H, Fox VL, Bousvaros A, Leichtner AM, Furuta GT. Source: The American Journal of Surgical Pathology. 1999 April; 23(4): 390-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10199468

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Ambulatory esophageal pH recording in gastroesophageal reflux: relevance to the development of esophagitis. Author(s): Rokkas T, Sladen GE. Source: The American Journal of Gastroenterology. 1988 June; 83(6): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3376916

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An etiological role for aeroallergens and eosinophils in experimental esophagitis. Author(s): Mishra A, Hogan SP, Brandt EB, Rothenberg ME. Source: The Journal of Clinical Investigation. 2001 January; 107(1): 83-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11134183

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Assessment of effectiveness of different dosage regimens of pantoprazole in controlling symptoms and healing esophageal lesions of patients with mild erosive esophagitis. Author(s): Moretzsohn LD, Brito EM, Reis MS, Coelho LG, Castro Lde P. Source: Arquivos De Gastroenterologia. 2002 April-June; 39(2): 123-5. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612717

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Association between gastroesophageal flap valve, reflux esophagitis, Barrett's epithelium, and atrophic gastritis assessed by endoscopy in Japanese patients. Author(s): Fujiwara Y, Higuchi K, Shiba M, Watanabe T, Tominaga K, Oshitani N, Matsumoto T, Arakawa T. Source: Journal of Gastroenterology. 2003; 38(6): 533-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825128

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Association of obesity with hiatal hernia and esophagitis. Author(s): Wilson LJ, Ma W, Hirschowitz BI. Source: The American Journal of Gastroenterology. 1999 October; 94(10): 2840-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10520831

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Autonomic nerve dysfunction is closely associated with the abnormalities of esophageal motility in reflux esophagitis. Author(s): Manabe N, Haruma K, Hata J, Nakamura K, Tanaka S, Chayama K. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678332

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Bacterial esophagitis associated with CD4+ T-lymphocytopenia without HIV infection. Possible role of corticosteroid treatment. Author(s): Richert SM, Orchard JL. Source: Digestive Diseases and Sciences. 1995 January; 40(1): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7821107

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Bacterial esophagitis in immunocompromised patients. Author(s): Walsh TJ, Belitsos NJ, Hamilton SR. Source: Archives of Internal Medicine. 1986 July; 146(7): 1345-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3718132

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Bacterial esophagitis: an often forgotten cause of odynophagia. Author(s): Ezzell JH Jr, Bremer J, Adamec TA. Source: The American Journal of Gastroenterology. 1990 March; 85(3): 296-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2309680

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Balloon dilation of double strictures after corrosive esophagitis. Author(s): Huang YC, Chen SJ, Hsu WM, Li YW, Ni YH. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 April; 32(4): 496-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11396823

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Barium studies in patients with Candida esophagitis: pseudoulcerations simulating viral esophagitis. Author(s): Glick SN. Source: Ajr. American Journal of Roentgenology. 1994 August; 163(2): 349-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8037028

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Barrett esophagus as an extension of severe esophagitis: analysis of radiologic signs in 29 cases. Author(s): Chen YM, Gelfand DW, Ott DJ, Wu WC. Source: Ajr. American Journal of Roentgenology. 1985 August; 145(2): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3875227

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Barrett's esophagus and reflux esophagitis: is there a missing link? Author(s): Cameron AJ, Arora AS. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866261

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Barrett's esophagus in patients with symptomatic reflux esophagitis. Author(s): Mann NS, Tsai MF, Nair PK. Source: The American Journal of Gastroenterology. 1989 December; 84(12): 1494-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2596449

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Benign esophageal stricture caused by diffuse severe esophagitis presenting as ascending fibrosis: report of a case. Author(s): Sashiyama H, Matsubara H, Koide Y, Matsubara H, Ochiai T, Isono K. Source: Surgery Today. 1998; 28(5): 538-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9607907

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Bile acids in reflux esophagitis. Author(s): Smith MR, Buckton GK, Bennett JR. Source: Gastroenterology. 1987 November; 93(5): 1145. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3653636

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Bile in the esophagus: a factor in the pathogenesis of reflux esophagitis in children. Author(s): Orel R, Markovic S. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 February; 36(2): 26673. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548065

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Bile salts in the esophagus of patients with esophagitis. Author(s): Johnsson F, Joelsson B, Floren CH, Nilsson A. Source: Scandinavian Journal of Gastroenterology. 1988 August; 23(6): 712-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3175533

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Biliopancreatic reflux esophagitis: the role of the Roux-en-Y long-limb diversion. Author(s): Topart P, Vandenbroucke F. Source: Chest Surg Clin N Am. 2001 August; 11(3): 605-18, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11787970

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Bismuth subsalicylate--an aid to the diagnosis and treatment of reflux esophagitis. Author(s): Bernstein RK. Source: Diabetes Care. 1984 July-August; 7(4): 404-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6468241

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Black esophagus associated with herpes esophagitis. Author(s): Cattan P, Cuillerier E, Cellier C, Carnot F, Landi B, Dusoleil A, Barbier JP. Source: Gastrointestinal Endoscopy. 1999 January; 49(1): 105-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9869733

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Bleeding reflux esophagitis: a prospective 1-year study in a university hospital. Author(s): Costa ND, Cadiot G, Merle C, Jolly D, Bouche O, Thiefin G, Zeitoun P. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197286

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Boerhaave's syndrome due to herpes simplex virus type 1 esophagitis in a patient with AIDS. Author(s): Dieckhaus KD, Hill DR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 May; 26(5): 1244-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9597273

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Bronchoesophageal fistula as a complication of cytomegalovirus esophagitis in AIDS. Author(s): Chalasani N, Parker KM, Wilcox CM. Source: Endoscopy. 1997 June; 29(5): S28-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9270936

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Brush cytology in the diagnosis of herpetic esophagitis. A case report. Author(s): Cardillo MR, Forte F. Source: Endoscopy. 1988 July; 20(4): 156-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3181087

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Bullous esophagitis due to chronic graft-versus-host disease. Author(s): Minocha A, Mandanas RA, Kida M, Jazzar A. Source: The American Journal of Gastroenterology. 1997 March; 92(3): 529-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9068490

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Candida esophagitis: risk factors in non-HIV population in Pakistan. Author(s): Yakoob J, Jafri W, Abid S, Jafri N, Islam M, Hamid S, Shah HA, Hussainy AS. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2328-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562403

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Carditis is associated with Helicobacter pylori-induced gastritis and not reflux esophagitis. Author(s): Jang TJ, Kim NI, Yang CH. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 26-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488703

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Caspofungin resistance in Candida albicans: correlating clinical outcome with laboratory susceptibility testing of three isogenic isolates serially obtained from a patient with progressive Candida esophagitis. Author(s): Hernandez S, Lopez-Ribot JL, Najvar LK, McCarthy DI, Bocanegra R, Graybill JR. Source: Antimicrobial Agents and Chemotherapy. 2004 April; 48(4): 1382-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15047549

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Celecoxib associated esophagitis: review of gastrointestinal side effects from cox-2 inhibitors. Author(s): Mantry P, Shah A, Sundaram U. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 61-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811211

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Clinical characteristics and natural history of patients with low-grade reflux esophagitis. Author(s): Manabe N, Yoshihara M, Sasaki A, Tanaka S, Haruma K, Chayama K. Source: Journal of Gastroenterology and Hepatology. 2002 September; 17(9): 949-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167114

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Clinical characteristics of Japanese reflux esophagitis patients as determined by Los Angeles classification. Author(s): Inamori M, Togawa J, Nagase H, Abe Y, Umezawa T, Nakajima A, Saito T, Ueno N, Tanaka K, Sekihara H, Kaifu H, Tsuboi H, Kayama H, Tominaga S, Nagura H. Source: Journal of Gastroenterology and Hepatology. 2003 February; 18(2): 172-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12542602

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Clinical findings and risk factors for Candida esophagitis in outpatients. Author(s): Underwood JA, Williams JW, Keate RF. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2003; 16(2): 66-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823199

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Clinical outcomes after laparoscopic antireflux surgery in patients with and without preoperative endoscopic esophagitis. Author(s): Desai KM, Frisella MM, Soper NJ. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 January; 7(1): 44-51; Discussion 51-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559184

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Clinical quiz. Esophageal stricture caused by reflux esophagitis. Author(s): Levy V, Nowicki MJ. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 November; 35(5): 668, 710. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487129

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Clinical response to amino acid-based formula in neurologically impaired children with refractory esophagitis. Author(s): Miele E, Staiano A, Tozzi A, Auricchio R, Paparo F, Troncone R. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 September; 35(3): 3149. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352519

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Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult subjects. Author(s): Okamoto K, Iwakiri R, Mori M, Hara M, Oda K, Danjo A, Ootani A, Sakata H, Fujimoto K. Source: Digestive Diseases and Sciences. 2003 December; 48(12): 2237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714607

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Clinicopathologic features of esophagitis in children. Author(s): Furuta GT. Source: Gastrointest Endosc Clin N Am. 2001 October; 11(4): 683-715, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689362

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Comparable efficacy of pantoprazole and omeprazole in patients with moderate to severe reflux esophagitis. Results of a multinational study. Author(s): Korner T, Schutze K, van Leendert RJ, Fumagalli I, Costa Neves B, Bohuschke M, Gatz G. Source: Digestion. 2003; 67(1-2): 6-13. Erratum In: Digestion. 2003; 67(3): 128. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743434

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Comparing lansoprazole and omeprazole in onset of heartburn relief: results of a randomized, controlled trial in erosive esophagitis patients. Author(s): Richter JE, Kahrilas PJ, Sontag SJ, Kovacs TO, Huang B, Pencyla JL. Source: The American Journal of Gastroenterology. 2001 November; 96(11): 3089-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721754

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Comparison of endoscopy with pathology in the diagnosis of esophagitis among children. Author(s): Rafeey M, Alyari A. Source: Indian J Gastroenterol. 2003 November-December; 22(6): 236. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030044

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Comparison of inter- and intraobserver consistency for grading of esophagitis by expert and trainee endoscopists. Author(s): Pandolfino JE, Vakil NB, Kahrilas PJ. Source: Gastrointestinal Endoscopy. 2002 November; 56(5): 639-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397269

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Corrosive esophagitis in children: a 30-year review. Author(s): de Jong AL, Macdonald R, Ein S, Forte V, Turner A. Source: International Journal of Pediatric Otorhinolaryngology. 2001 March; 57(3): 20311. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11223452

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Cost-effectiveness of proton-pump inhibitors for maintenance therapy of erosive reflux esophagitis. Author(s): Dean BB, Siddique RM, Yamashita BD, Bhattacharjya AS, Ofman JJ. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 July 15; 58(14): 1338-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11471482

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COX-2 inhibition in esophagitis, Barrett's esophagus and esophageal cancer. Author(s): Piazuelo E, Jimenez P, Lanas A. Source: Current Pharmaceutical Design. 2003; 9(27): 2267-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552327

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Cytomegalovirus acute necrotizing esophagitis. Author(s): Barjas E, Pires S, Lopes J, Valente A, Oliveira E, Palma R, Raimundo M, Alexandrino P, Moura MC. Source: Endoscopy. 2001 August; 33(8): 735. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490397

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Daily low-dose versus alternate day full-dose lansoprazole in the maintenance treatment of reflux esophagitis. Author(s): Baldi F, Morselli-Labate AM, Cappiello R, Ghersi S; Italian Lansoprazole Study Group. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094850

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Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Author(s): Namiot Z, Sarosiek J, Marcinkiewicz M, Edmunds MC, McCallum RW. Source: Digestive Diseases and Sciences. 1994 December; 39(12): 2523-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7995174

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Defunctionalized jejunal loops have been preferred to avoid reflux and esophagitis after total gastrectomy and to prevent stricture and cholangitis after anastomosis of the biliary tree with the digestive tract. Author(s): Defelitto JR. Source: World Journal of Surgery. 1999 September; 23(9): 983-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10449833

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De-Nol in the treatment of reflux esophagitis. Author(s): Balan G, Sandulescu E, Cijevschi C, Stanciu R, Darwish R, Stanciu C. Source: Rev Med Chir Soc Med Nat Iasi. 1989 January-March; 93(1): 67-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2682898

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Detection of esophagitis by 99mTc-methoxyisobutylisonitrile chest SPECT. Author(s): Kao CH, Hsieh JF, Tsai SC, Ho YJ, Sun SS. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2000 December; 41(12): 1969-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138680

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Detection of esophagitis by technetium 99m tetrofosmin chest SPECT. Author(s): Kao CH, ChangLai SP, Lee JK. Source: The American Journal of Gastroenterology. 2001 June; 96(6): 1950-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11419868

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Detrimental impact of acid and pepsin on the rate of luminal release of transforming growth factor alpha. Its potential pathogenetic role in the development of reflux esophagitis. Author(s): Marcinkiewicz M, Namiot Z, Edmunds MC, McCallum RW, Sarosiek J. Source: Journal of Clinical Gastroenterology. 1996 December; 23(4): 261-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8957727

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Diagnosis and management of infectious esophagitis associated with human immunodeficiency virus infection. Author(s): Zaidi SA, Cervia JS. Source: J Int Assoc Physicians Aids Care (Chic Ill). 2002 Spring; 1(2): 53-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942677

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Diagnosis and treatment of esophagitis in AIDS. Author(s): Monkemuller KE, Wilcox CM. Source: Compr Ther. 2000 Fall; 26(3): 163-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984820

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Differences in manometry and 24-H ambulatory pH-metry between patients with and without endoscopic or histological esophagitis in gastroesophageal reflux disease. Author(s): Kasapidis P, Xynos E, Mantides A, Chrysos E, Demonakou M, Nikolopoulos N, Vassilakis JS. Source: The American Journal of Gastroenterology. 1993 November; 88(11): 1893-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8237938

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Diminished luminal release of esophageal epidermal growth factor in patients with reflux esophagitis. Author(s): Rourk RM, Namiot Z, Edmunds MC, Sarosiek J, Yu Z, McCallum RW. Source: The American Journal of Gastroenterology. 1994 August; 89(8): 1177-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8053431

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Does diabetic autonomic neuropathy influence the clinical manifestations of reflux esophagitis? Author(s): Antwi Ch, Krahulec B, Michalko L, Strbova L, Hlinstakova S, Balazovjech I. Source: Bratisl Lek Listy. 2003; 104(4-5): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604253

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Does healing of esophagitis improve esophageal motor function? Author(s): Eckardt VF. Source: Digestive Diseases and Sciences. 1988 February; 33(2): 161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3338364

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Does pH monitoring predict clinical course in esophagitis? Author(s): Robinson M. Source: Gastroenterology. 1992 May; 102(5): 1816. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1568597

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Dosimetric correlates for acute esophagitis in patients treated with radiotherapy for lung carcinoma. Author(s): Bradley J, Deasy JO, Bentzen S, El-Naqa I. Source: International Journal of Radiation Oncology, Biology, Physics. 2004 March 15; 58(4): 1106-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001251

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Doxicycline-induced esophagitis: treatment with liquid sucralphate. Author(s): Pinos T, Figueras C, Mas R. Source: The American Journal of Gastroenterology. 1990 July; 85(7): 902-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2371996

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Doxycycline-induced hemorrhagic esophagitis: a pediatric case. Author(s): Kato S, Kobayashi M, Sato H, Saito Y, Komatsu K, Harada Y. Source: Journal of Pediatric Gastroenterology and Nutrition. 1988 September-October; 7(5): 762-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3183880

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Drug-induced esophagitis. Author(s): Eng J, Sabanathan S. Source: The American Journal of Gastroenterology. 1991 September; 86(9): 1127-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1882789

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Duodenal content reflux esophagitis in the rat: an animal model for the ulcerassociated cell lineage (UACL)? Author(s): Hanby AM, Pera M, Filipe I, Duranceau A, Wright NA, Pera M, Grande L, Poulsom R. Source: American Journal of Pathology. 1997 December; 151(6): 1819-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9403733

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Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: a post hoc analysis of eight double blind prospective studies. Author(s): Laine L, Sugg J. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 2992-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492181

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Effect of long-term, continuous versus alternate-day omeprazole therapy on serum gastrin in patients treated for reflux esophagitis. Author(s): Ligumsky M, Lysy J, Siguencia G, Friedlander Y. Source: Journal of Clinical Gastroenterology. 2001 July; 33(1): 32-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11418787

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Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Author(s): Richter JE, Kahrilas PJ, Johanson J, Maton P, Breiter JR, Hwang C, Marino V, Hamelin B, Levine JG; Esomeprazole Study Investigators. Source: The American Journal of Gastroenterology. 2001 March; 96(3): 656-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11280530

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Efficacy and safety of oral pantoprazole 20 mg given once daily for reflux esophagitis in children. Author(s): Madrazo-de la Garza A, Dibildox M, Vargas A, Delgado J, Gonzalez J, Yanez P. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 February; 36(2): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548064

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Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Author(s): Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 777-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738455

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Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis. Author(s): Isomoto H, Wang A, Mizuta Y, Akazawa Y, Ohba K, Omagari K, Miyazaki M, Murase K, Hayashi T, Inoue K, Murata I, Kohno S. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650786

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Endoscopic diagnosis and classification of reflux esophagitis: are we there yet? Author(s): Boyce HW. Source: Gastrointestinal Endoscopy. 2002 November; 56(5): 775-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397301

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Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies. Author(s): Hirota S, Tsujino K, Hishikawa Y, Watanabe H, Kono K, Soejima T, Obayashi K, Takada Y, Kono M, Abe M. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 2001 March; 58(3): 273-8. Erratum In: Radiother Oncol 2001 July; 60(1): 107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11230888

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Eosinophilic esophagitis associated with anastomotic strictures after esophageal atresia repair. Author(s): Batres LA, Liacouras C, Schnaufer L, Mascarenhas MR. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 August; 35(2): 224-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187303

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Eosinophilic esophagitis: it's not just kid's stuff. Author(s): Fox VL, Nurko S, Furuta GT. Source: Gastrointestinal Endoscopy. 2002 August; 56(2): 260-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145607

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Eosinophilic esophagitis: strictures, impactions, dysphagia. Author(s): Khan S, Orenstein SR, Di Lorenzo C, Kocoshis SA, Putnam PE, Sigurdsson L, Shalaby TM. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 22-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645786

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Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety. Author(s): Johnson DA, Benjamin SB, Vakil NB, Goldstein JL, Lamet M, Whipple J, Damico D, Hamelin B. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 27-34. Erratum In: Am J Gastroenterol 2001 March; 96(3): 942. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197282

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Esophageal cancer complicated by cytomegalovirus esophagitis during chemoradiotherapy: case report. Author(s): Ohnuma H, Sato Y, Takayama T, Takimoto R, Abe T, Hagiwara S, Kukitsu T, Nobuoka A, Sato T, Kogawa K, Kato J, Niitsu Y. Source: Gastrointestinal Endoscopy. 2003 April; 57(4): 622-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665790

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Esophagitis dessicans superficialis with bulla in chronic renal failure: a case report. Author(s): Devarbhavi H, Alvares JF. Source: Gastrointestinal Endoscopy. 2001 August; 54(2): 256-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474407

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Esophagitis dissecans superficialis associated with celiac disease. Author(s): Hage-Nassar G, Rotterdam H, Frank D, Green PH. Source: Gastrointestinal Endoscopy. 2003 January; 57(1): 140-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518158

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Esophagitis in distressed infants: poor diagnostic agreement between esophageal pH monitoring and histopathologic findings. Author(s): Heine RG, Cameron DJ, Chow CW, Hill DJ, Catto-Smith AG. Source: The Journal of Pediatrics. 2002 January; 140(1): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11815758

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Esophagitis with an inflammatory polyp. Author(s): Bach KK, Postma GN, Koufman JA. Source: Ear, Nose, & Throat Journal. 2002 December; 81(12): 824. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516374

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EUS and histopathologic correlates in eosinophilic esophagitis. Author(s): Stevoff C, Rao S, Parsons W, Kahrilas PJ, Hirano I. Source: Gastrointestinal Endoscopy. 2001 September; 54(3): 373-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522985

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Evaluation of esophageal motility by endosonography using a miniature ultrasonographic probe in patients with reflux esophagitis. Author(s): Manabe N, Haruma K, Hata J, Kusunoki H, Yoshida S, Futagami K, Tanaka S, Chayama K. Source: Scandinavian Journal of Gastroenterology. 2002 June; 37(6): 674-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126245

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Exfoliative esophagitis early after autologous peripheral blood stem cell transplantation. Author(s): Hashino S, Chiba K, Toyoshima N, Suzuki S, Kurosawa M, Musashi M, Asaka M. Source: International Journal of Hematology. 2001 December; 74(4): 461-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794705

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Factors influencing corpus argyrophil cell density and hyperplasia in reflux esophagitis patients treated with antisecretory drugs and controls. Author(s): Diebold MD, Richardson S, Duchateau A, Bigard MA, Colin R, Cortot A, Fauchere JL, Zeitoun P. Source: Digestive Diseases and Sciences. 1998 August; 43(8): 1629-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9724142

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Factors predicting relapse during maintenance treatment with famotidine in patients with healed reflux esophagitis. Dutch Esophagitis Study Group. Author(s): Wesdorp IC, Dekker W, Festen HP. Source: Clinical Therapeutics. 1997 September-October; 19(5): 1048-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9385492

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Failed Nissen fundoplication in two patients who had persistent vomiting and eosinophilic esophagitis. Author(s): Liacouras CA. Source: Journal of Pediatric Surgery. 1997 October; 32(10): 1504-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9349784

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Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis. Author(s): Olden K, Triadafilopoulos G. Source: The American Journal of Gastroenterology. 1991 September; 86(9): 1142-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1679286

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Failure of long limb Roux-en-Y reconstruction to prevent alkaline reflux esophagitis after total gastrectomy. Author(s): Salo JA, Kivilaakso E. Source: Endoscopy. 1990 March; 22(2): 65-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2335144

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Failure of sucralfate in the treatment of refractory esophagitis versus high-dose famotidine. An endoscopic study. Author(s): Pace F, Lazzaroni M, Bianchi Porro G. Source: Scandinavian Journal of Gastroenterology. 1991 May; 26(5): 491-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1871541

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Fatal Candida esophagitis in two diabetics after renal transplantation. Author(s): Jones JM, Glass NR, Belzer FO. Source: Archives of Surgery (Chicago, Ill. : 1960). 1982 April; 117(4): 499-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7039554

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Fatal necrotizing esophagitis due to Penicillium chrysogenum in a patient with acquired immunodeficiency syndrome. Author(s): Hoffman M, Bash E, Berger SA, Burke M, Yust I. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1992 December; 11(12): 1158-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1291312

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Fistulization between the esophagus, aorta, and trachea as a complication of acute corrosive esophagitis: report of a case. Author(s): McCabe RE Jr, Scott JR, Knox WG. Source: The American Surgeon. 1969 June; 35(6): 450-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5770217

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Fixed transverse folds in the esophagus: a sign of reflux esophagitis. Author(s): Levine MS, Goldstein HM. Source: Ajr. American Journal of Roentgenology. 1984 August; 143(2): 275-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6611055

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Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial. Author(s): Laine L, Dretler RH, Conteas CN, Tuazon C, Koster FM, Sattler F, Squires K, Islam MZ. Source: Annals of Internal Medicine. 1992 October 15; 117(8): 655-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1308663

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Fluconazole in the treatment of mycotic oropharyngeal stomatitis and esophagitis in neutropenic cancer patients. Author(s): Krcmery V Jr, Koza I, Hornikova M, Fuchsberger P, Spanik S, Mardiak J, Sufliarsky J, Blahova M, Savko V, Migom C. Source: Chemotherapy. 1991; 37(5): 343-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1804594

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Fluconazole versus itraconazole for candida esophagitis in acquired immunodeficiency syndrome. Candida Esophagitis. Author(s): Barbaro G, Barbarini G, Calderon W, Grisorio B, Alcini P, Di Lorenzo G. Source: Gastroenterology. 1996 November; 111(5): 1169-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8898629

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Fluconazole vs itraconazole-flucytosine association in the treatment of esophageal candidiasis in AIDS patients. A double-blind, multicenter placebo-controlled study. The Candida Esophagitis Multicenter Italian Study (CEMIS) Group. Author(s): Barbaro G, Barbarini G, Di Lorenzo G. Source: Chest. 1996 December; 110(6): 1507-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8989069

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Food sensitivity in reflux esophagitis. Author(s): Price SF, Smithson KW, Castell DO. Source: Gastroenterology. 1978 August; 75(2): 240-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=27414

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Foscarnet in the treatment of cytomegalovirus esophagitis. Author(s): Nelson MR, Hawkins DA, Gazzard BG. Source: The American Journal of Medicine. 1993 April; 94(4): 446-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8386438

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Fragility of the esophageal mucosa: a pathognomonic endoscopic sign of primary eosinophilic esophagitis? Author(s): Straumann A, Rossi L, Simon HU, Heer P, Spichtin HP, Beglinger C. Source: Gastrointestinal Endoscopy. 2003 March; 57(3): 407-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612531

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Fundoplication for reflux esophagitis: misadventures with the operation of choice. Author(s): Polk HC Jr. Source: Annals of Surgery. 1976 June; 183(6): 645-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9914

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Fungal esophagitis in children. Author(s): Young C, Chang MH, Chen JM. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1993 November-December; 34(6): 436-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8296555

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Future medical therapy of reflux esophagitis. Author(s): Castell DO. Source: Journal of Clinical Gastroenterology. 1986; 8 Suppl 1: 81-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2874169

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Galactorrhea caused by esophagitis. Author(s): Turton DB, Shakir KM. Source: American Journal of Obstetrics and Gynecology. 1995 November; 173(5): 162930. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7503216

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Gallium-67 imaging in candidal esophagitis. Author(s): Rundback JH, Goldfarb CR, Ongseng F. Source: Clinical Nuclear Medicine. 1990 January; 15(1): 38-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2306897

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Gastric accommodation studied by ultrasonography in patients with reflux esophagitis. Author(s): Tefera S, Gilja OH, Hatlebakk JG, Berstad A. Source: Digestive Diseases and Sciences. 2001 March; 46(3): 618-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318542

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Gastric acid secretion and pattern of gastroesophageal reflux in patients with esophagitis and concomitant duodenal ulcer. A multivariate analysis of pathogenetic factors. Author(s): Zhu H, Pace F, Sangaletti O, Bianchi Porro G. Source: Scandinavian Journal of Gastroenterology. 1993 May; 28(5): 387-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8511498

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Gastric acidity and gastroesophageal reflux patterns in patients with esophagitis. Author(s): Fiorucci S, Santucci L, Chiucchiu S, Morelli A. Source: Gastroenterology. 1992 September; 103(3): 855-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1499935

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Gastric and esophageal acidity during continuous treatment with H2-antagonists in uncomplicated esophagitis. Author(s): Fiorucci S, Santucci L, Perrone E, Abbritti F, Morelli A. Source: Scandinavian Journal of Gastroenterology. 1989 August; 24(6): 671-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2573143

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Gastric cardia inflammation and intestinal metaplasia: associations with reflux esophagitis and Helicobacter pylori. Author(s): Goldstein NS, Karim R. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1999 November; 12(11): 1017-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574598

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Gastric emptying in patients with severe reflux esophagitis. Author(s): Keshavarzian A, Bushnell DL, Sontag S, Yegelwel EJ, Smid K. Source: The American Journal of Gastroenterology. 1991 June; 86(6): 738-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2038997

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Gastric Helicobacter pylori infection accelerates healing of reflux esophagitis during treatment with the proton pump inhibitor pantoprazole. Author(s): Holtmann G, Cain C, Malfertheiner P. Source: Gastroenterology. 1999 July; 117(1): 11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10381904

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Gastric symptoms and duodenogastric reflux in patients referred for gastroesophageal reflux symptoms and endoscopic esophagitis. Author(s): Romagnoli R, Collard JM, Bechi P, Salizzoni M. Source: Surgery. 1999 May; 125(5): 480-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10330935

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Gastric ulcers associated with herpes simplex esophagitis in a nonimmunocompromised patient. Author(s): al-Samman M, Zuckerman MJ, Verghese A, Boman D. Source: Journal of Clinical Gastroenterology. 1994 March; 18(2): 160. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8189014

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Gastroesophageal reflux and esophagitis in infants and children. Author(s): Groben PA, Siegal GP, Shub MD, Ulshen MH, Askin FB. Source: Perspectives in Pediatric Pathology. 1987; 11: 124-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3299248

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Gastroesophageal reflux and esophagitis-associated hypertrophic osteoarthropathy. Author(s): Rosario N, Farias L. Source: Journal of Pediatric Gastroenterology and Nutrition. 1998 July; 27(1): 125. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9669746

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Gastroesophageal reflux and esophagitis-associated hypertrophic osteoarthropathy. Author(s): Greenwald M, Couper R, Laxer R, Durie P, Silverman E. Source: Journal of Pediatric Gastroenterology and Nutrition. 1996 August; 23(2): 178-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8856586

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Gastroesophageal reflux disease is a common cause of noncardiac chest pain in a country with a low prevalence of reflux esophagitis. Author(s): Ho KY, Ng WL, Kang JY, Yeoh KG. Source: Digestive Diseases and Sciences. 1998 September; 43(9): 1991-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753264

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Gastroesophageal scintigraphy and endoscopy in the diagnosis of esophageal reflux and esophagitis. Author(s): Fung WP, Van der Schaaf A, Grieve JC. Source: The American Journal of Gastroenterology. 1985 April; 80(4): 245-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3984990

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Gastrointestinal hormone in dumping syndrome and reflux esophagitis after gastric surgery. Author(s): Yamashita Y, Toge T, Adrian TE. Source: J Smooth Muscle Res. 1997 April; 33(2): 37-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9403815

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Gastro-oesophageal reflux and esophagitis in cystic fibrosis. Author(s): Feigelson J, Girault F, Pecau Y. Source: Acta Paediatr Scand. 1987 November; 76(6): 989-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3425319

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Gastroplasty in patients with symptoms of reflux esophagitis. Author(s): Simonowitz DA, Dellinger EP, Stothert JC, Pitts A. Source: Surg Gynecol Obstet. 1982 February; 154(2): 235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7058485

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Grasp biopsy, suction biopsy, and clinical history in the evaluation of esophagitis in infants 0-6 months of age. Author(s): Friesen CA, Zwick DL, Streed CJ, Zalles C, Roberts CC. Source: Journal of Pediatric Gastroenterology and Nutrition. 1995 April; 20(3): 300-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7608824

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H. pylori and reflux esophagitis in Turkish patients living in the Zaanstreek region in the Netherlands. Author(s): Loffeld RJ. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1846-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561012

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Healing, relapse rates and prophylaxis of reflux esophagitis. Author(s): Glise H. Source: Scandinavian Journal of Gastroenterology. Supplement. 1989; 156: 57-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2568016

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Heartburn severity underestimates erosive esophagitis severity in elderly patients with gastroesophageal reflux disease. Author(s): Johnson DA, Fennerty MB. Source: Gastroenterology. 2004 March; 126(3): 660-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988819

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Helicobacter pylori infection and reflux esophagitis in children with chronic asthma. Author(s): Nijevitch AA, Loguinovskaya VV, Tyrtyshnaya LV, Sataev VU, Ogorodnikova IN, Nuriakhmetova AN. Source: Journal of Clinical Gastroenterology. 2004 January; 38(1): 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679321

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Helicobacter pylori infection and reflux esophagitis in children with chronic asthma. Author(s): Sontag SJ. Source: Journal of Clinical Gastroenterology. 2004 January; 38(1): 3-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679318

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Helicobacter pylori infection and reflux esophagitis in children. Author(s): Ozcay F, Gurakan F, Demir H, Saltik IN, Ozen H, Yuce A, Kocak N. Source: Helicobacter. 2002 October; 7(5): 328-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390215

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Herpes simplex esophagitis from 1307 autopsy cases. Author(s): Itoh T, Takahashi T, Kusaka K, Kawaura K, Nakagawa Y, Yamakawa J, Kanda T. Source: Journal of Gastroenterology and Hepatology. 2003 December; 18(12): 1407-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675270

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Herpes simplex esophagitis in immunocompetent individuals. Author(s): Ashar-Sampat U, Desai D, Bhaduri A, Joshi A, Udwadia ZF. Source: Indian J Gastroenterol. 2001 November-December; 20(6): 245-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817783

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Herpes simplex esophagitis in patients with liver disease. Author(s): Pauwels A, Carbonell N, Galula G, Mohand-Mamar D, Maury E, de LajartheThirouard AS, Levy VG, Poupon R. Source: Digestive Diseases and Sciences. 2002 October; 47(10): 2189-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395891

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Herpes simplex viral infection presenting as fever of unknown origin and esophagitis in a renal transplant patient. Author(s): Gelman R, Khankin E, Ben-Itzhak A, Finkelshtein R, Nakhoul F. Source: Isr Med Assoc J. 2002 November; 4(11 Suppl): 970-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455194

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Herpes simplex virus esophagitis in an immunocompetent host with sepsis. Author(s): Pamuk ON, Pamuk GE, Celik AF, Ozturk R, Aktuglu Y. Source: The American Journal of Gastroenterology. 2001 July; 96(7): 2264-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467669

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Herpetic esophagitis and intractable hiccups (singultus) in an immunocompetent patient. Author(s): Mulhall BP, Nelson B, Rogers L, Wong RK. Source: Gastrointestinal Endoscopy. 2003 May; 57(6): 796-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739568

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Hiatal hernia size is the dominant determinant of esophagitis presence and severity in gastroesophageal reflux disease. Author(s): Jones MP, Sloan SS, Rabine JC, Ebert CC, Huang CF, Kahrilas PJ. Source: The American Journal of Gastroenterology. 2001 June; 96(6): 1711-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11419819

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High dose Omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia. Author(s): Sheth NP. Source: Journal of Pediatric Surgery. 2002 June; 37(6): 946. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037776

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High incidence of noninfectious esophagitis in orthotopic liver transplant (OLT) recipients. Author(s): Karasu Z, Hulagu S, Gurakar A, Jazzar A, Kerwin B, Taydas E, McMillon G, Sebastian A, Wright H, Nour B. Source: J Okla State Med Assoc. 2001 February; 94(2): 43-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11288461

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High incidence of reflux esophagitis observed by routine endoscopic examination after gastric pull-up esophagectomy. Author(s): Shibuya S, Fukudo S, Shineha R, Miyazaki S, Miyata G, Sugawara K, Mori T, Tanabe S, Tonotsuka N, Satomi S. Source: World Journal of Surgery. 2003 May; 27(5): 580-3. Epub 2003 April 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715227

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High-dose omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia. Author(s): Van Biervliet S, Van Winckel M, Robberecht E, Kerremans I. Source: Journal of Pediatric Surgery. 2001 September; 36(9): 1416-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11528618

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High-resolution EUS in children with eosinophilic "allergic" esophagitis. Author(s): Fox VL, Nurko S, Teitelbaum JE, Badizadegan K, Furuta GT. Source: Gastrointestinal Endoscopy. 2003 January; 57(1): 30-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518127

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Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children. Author(s): Esposito S, Valente G, Zavallone A, Guidali P, Rapa A, Oderda G. Source: Human Pathology. 2004 January; 35(1): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745730

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Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective, population-based study. Author(s): Ruhl CE, Sonnenberg A, Everhart JE. Source: Annals of Epidemiology. 2001 October; 11(7): 477-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557179

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Iatrogenic esophagitis. Author(s): Kalar JG, Redwine JN, Persaud MV. Source: Iowa Med. 1988 July; 78(7): 323-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3215741

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Iatrogenic esophagitis. Author(s): Arora AS, Murray JA. Source: Current Gastroenterology Reports. 2000 June; 2(3): 224-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10957934

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Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. Author(s): Straumann A, Bauer M, Fischer B, Blaser K, Simon HU. Source: The Journal of Allergy and Clinical Immunology. 2001 December; 108(6): 954-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742273

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Idiopathic eosinophilic esophagitis with stricture formation in a patient with longstanding eosinophilic gastroenteritis. Author(s): Mahajan L, Wyllie R, Petras R, Steffen R, Kay M. Source: Gastrointestinal Endoscopy. 1997 December; 46(6): 557-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9434228

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Image of the month. Adherent, yellow exudate speckled with black spots in the distal two thirds of the esophagus. Diagnosis: This distinctive endoscopic image shows an acute necrotizing esophagitis, also known as the black esophagus. Author(s): Baffy G, Strate LL, Krnsky ML. Source: Gastroenterology. 2000 February; 118(2): 252, 453. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10691371

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Images in clinical medicine. Herpes simplex esophagitis. Author(s): Urbano FL, Nguyen MT. Source: The New England Journal of Medicine. 1999 April 22; 340(16): 1254. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210710

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Impact of esophageal bile exposure on the genesis of reflux esophagitis in the absence of gastric acid after total gastrectomy. Author(s): Yumiba T, Kawahara H, Nishikawa K, Inoue Y, Ito T, Matsuda H. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1647-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135013

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Improper alendronate administration and a case of pill esophagitis. Author(s): Rimmer DE, Rawls DE. Source: The American Journal of Gastroenterology. 1996 December; 91(12): 2648-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8947013

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In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus. Author(s): Jackle S, Gladkova N, Feldchtein F, Terentieva A, Brand B, Gelikonov G, Gelikonov V, Sergeev A, Fritscher-Ravens A, Freund J, Seitz U, Schroder S, Soehendra N. Source: Endoscopy. 2000 October; 32(10): 750-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11068833

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Incidence and treatment of candida esophagitis in patients undergoing renal transplantation. Data from the Minnesota prospective randomized trial of cyclosporine versus antilymphocyte globulin-azathioprine. Author(s): Frick T, Fryd DS, Goodale RL, Simmons RL, Sutherland DE, Najarian JS. Source: American Journal of Surgery. 1988 February; 155(2): 311-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3277475

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Increased acid and bile reflux in Barrett's esophagus compared to reflux esophagitis, and effect of proton pump inhibitor therapy. Author(s): Menges M, Muller M, Zeitz M. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 331-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232672

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Increased levels of prostaglandins and nitric oxide in esophageal mucosa of children with reflux esophagitis. Author(s): Zicari A, Corrado G, Cavaliere M, Frandina G, Rea P, Pontieri G, Cardi E, Cucchiara S. Source: Journal of Pediatric Gastroenterology and Nutrition. 1998 February; 26(2): 194-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9481637

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Infectious esophagitis following liver and renal transplantation. Author(s): Alexander JA, Brouillette DE, Chien MC, Yoo YK, Tarter RE, Gavaler JS, Van Thiel DH. Source: Digestive Diseases and Sciences. 1988 September; 33(9): 1121-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2842120

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Infectious necrotizing esophagitis: outcome after medical and surgical intervention. Author(s): Gaissert HA, Roper CL, Patterson GA, Grillo HC. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 342-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607636

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Infiltrating eosinophils and eotaxin: their association with idiopathic eosinophilic esophagitis. Author(s): Fujiwara H, Morita A, Kobayashi H, Hamano K, Fujiwara Y, Hirai K, Yano M, Naka T, Saeki Y. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 October; 89(4): 429-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392390

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Influence of Helicobacter pylori infection on the prevalence of reflux esophagitis in Japanese patients. Author(s): Fujishiro H, Adachi K, Kawamura A, Katsube T, Ono M, Yuki M, Amano K, Ishihara S, Kinoshita Y. Source: Journal of Gastroenterology and Hepatology. 2001 November; 16(11): 1217-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903738

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Inlet patch: prevalence, histologic type, and association with esophagitis, Barrett esophagus, and antritis. Author(s): Tang P, McKinley MJ, Sporrer M, Kahn E. Source: Archives of Pathology & Laboratory Medicine. 2004 April; 128(4): 444-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043461

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Is a proton pump inhibitor necessary for the treatment of lower-grade reflux esophagitis? Author(s): Soga T, Matsuura M, Kodama Y, Fujita T, Sekimoto I, Nishimura K, Yoshida S, Kutsumi H, Fujimoto S. Source: Journal of Gastroenterology. 1999 August; 34(4): 435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452673

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Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis? Author(s): Coenraad M, Masclee AA, Straathof JW, Ganesh S, Griffioen G, Lamers CB. Source: The American Journal of Gastroenterology. 1998 July; 93(7): 1068-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9672332

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Is lansoprazole (Prevacid) or omeprazole (Prilosec) more effective in treating erosive esophagitis? Author(s): Kim JD. Source: The Journal of Family Practice. 2002 April; 51(4): 384. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978268

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Jejunal interposition for reflux esophagitis and esophageal stricture unresponsive to valvuloplasty. Author(s): Gergely M. Source: World Journal of Surgery. 1982 May; 6(3): 377-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7113243

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Jejunal interposition for reflux esophagitis and esophageal stricture unresponsive to valvuloplasty. Author(s): Polk HC Jr. Source: World Journal of Surgery. 1980 November; 4(6): 731-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7233941

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Ketoconazole treatment of Candida esophagitis--a prospective study of 12 cases. Author(s): Fazio RA, Wickremesinghe PC, Arsura EL. Source: The American Journal of Gastroenterology. 1983 May; 78(5): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6303114

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Ketoconazole-resistant Candida esophagitis in patients with acquired immunodeficiency syndrome. Author(s): Tavitian A, Raufman JP, Rosenthal LE, Weber J, Webber CA, Dincsoy HP. Source: Gastroenterology. 1986 February; 90(2): 443-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3510145

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Lansoprazole heals erosive reflux esophagitis resistant to histamine H2-receptor antagonist therapy. Author(s): Sontag SJ, Kogut DG, Fleischmann R, Campbell DR, Richter J, Robinson M, McFarland M, Sabesin S, Lehman GA, Castell D. Source: The American Journal of Gastroenterology. 1997 March; 92(3): 429-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9068463

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Lansoprazole prevents recurrence of erosive reflux esophagitis previously resistant to H2-RA therapy. The Lansoprazole Maintenance Study Group. Author(s): Sontag SJ, Kogut DG, Fleischmann R, Campbell DR, Richter J, Haber M. Source: The American Journal of Gastroenterology. 1996 September; 91(9): 1758-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792694

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Lansoprazole versus omeprazole in the treatment of reflux esophagitis. Author(s): Vcev A, Stimac D, Vceva A, Rubinic M, Ivandic A, Ivanis N, Horvat D, Volaric M, Karner I. Source: Acta Med Croatica. 1997; 51(3): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9248117

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Laparoscopic repair for simple ulcerative esophagitis: current results. Author(s): Tirnaksiz MB, Deschamps C. Source: Chest Surg Clin N Am. 2001 August; 11(3): 547-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11787966

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Laparoscopic surgery for reflux esophagitis and paraesophageal hernia. Author(s): Balsara KP, Shah CR, Bhandari M. Source: Indian J Gastroenterol. 2002 May-June; 21(3): 102-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118920

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Learning more about eosinophilic esophagitis. Author(s): Elitsur Y. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 November; 35(5): 7112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487120

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Letter: Reflux esophagitis. Author(s): Greenwald AJ. Source: Jama : the Journal of the American Medical Association. 1976 March 15; 235(11): 1106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=946198

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Lichen planus esophagitis with secondary candidiasis: successful combination treatment with ketoconazole and a corticosteroid. Author(s): Ali A, Runzi M, Rosien U, Goebell H, Layer P. Source: Endoscopy. 1996 June; 28(5): 460. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8858239

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Lichen planus esophagitis: report of three patients treated with oral tacrolimus or intraesophageal corticosteroid injections or both. Author(s): Keate RF, Williams JW, Connolly SM. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2003; 16(1): 47-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581256

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Limited value of typical gastroesophageal reflux disease symptoms to screen for erosive esophagitis in Taiwanese. Author(s): Lin BR, Wong JM, Yang JC, Wang JT, Lin JT, Wang TH. Source: J Formos Med Assoc. 2003 May; 102(5): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874667

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Localized proximal esophagitis secondary to ascorbic acid ingestion and esophageal motor disorder. Author(s): Walta DC, Giddens JD, Johnson LF, Kelley JL, Waugh DF. Source: Gastroenterology. 1976 May; 70(5 Pt.1): 766-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=131047

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Long-term clinical outcome of elderly patients with reflux esophagitis: a six-month to three-year follow-up study. Author(s): Pilotto A, Franceschi M, Leandro G, Novello R, Di Mario F, Valerio G. Source: American Journal of Therapeutics. 2002 July-August; 9(4): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115018

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Long-term comparison of antireflux surgery versus conservative therapy for reflux esophagitis. Author(s): Isolauri J, Luostarinen M, Viljakka M, Isolauri E, Keyrilainen O, Karvonen AL. Source: Annals of Surgery. 1997 March; 225(3): 295-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9060586

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Long-term therapy for reflux esophagitis. Author(s): Tytgat GN. Source: The New England Journal of Medicine. 1995 October 26; 333(17): 1148-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7565956

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Long-term treatment of erosive esophagitis with omeprazole: does it work? Author(s): Rabeneck L. Source: Gastroenterology. 1995 February; 108(2): 613-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7835610

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Long-term use of acid-suppressive therapy after the endoscopic diagnosis of reflux esophagitis. Author(s): Boom HD, Loffeld RJ. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(4): 271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11284972

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Low-dose omeprazole for erosive esophagitis. Author(s): Epling J, Taylor H. Source: The Journal of Family Practice. 1999 February; 48(2): 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10037536

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Lower esophageal sphincter in reflux esophagitis. Author(s): Scheurer U, Halter F. Source: Scandinavian Journal of Gastroenterology. 1976; 11(6): 629-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=981968

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Lowering the risk of esophagitis from alendronate therapy. Author(s): Chase JL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1998 May 1; 55(9): 892-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9588247

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Management of reflux esophagitis with stricture. Author(s): Murray GF, Williams LE, Wilcox BR, Starek PJ. Source: N C Med J. 1975 December; 36(12): 729-30. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1059881

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Massive gastrointestinal hemorrhage due to Candida esophagitis. Author(s): Kaplan D, Warren J. Source: The American Journal of Gastroenterology. 1988 April; 83(4): 463-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3258122

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Medical and surgical management of reflux esophagitis. A 38-month report of a prospective clinical trial. Author(s): Behar J, Sheahan DG, Biancani P, Spiro HM, Storer EH. Source: The New England Journal of Medicine. 1975 August 7; 293(6): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=237234

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Medical or surgical therapy for erosive reflux esophagitis: cost-utility analysis using a Markov model. Author(s): Romagnuolo J, Meier MA, Sadowski DC. Source: Annals of Surgery. 2002 August; 236(2): 191-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170024

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Medication bezoar and esophagitis in a patient with HIV infection receiving combination antiretroviral therapy. Author(s): Hutter D, Akgun S, Ramamoorthy R, Dever LL. Source: The American Journal of Medicine. 2000 June 1; 108(8): 684-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10896628

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Methotrexate-induced esophagitis in a child with Crohn disease. Author(s): Batres LA, Gabriel CA, Tsou VM. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 October; 37(4): 514-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508226

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Miniprobe ultrasonography for determining prognosis in corrosive esophagitis. Author(s): Kamijo Y, Kondo I, Kokuto M, Kataoka Y, Soma K. Source: The American Journal of Gastroenterology. 2004 May; 99(5): 851-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128349

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Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2PL) gene therapy. Author(s): Epperly MW, Gretton JA, DeFilippi SJ, Greenberger JS, Sikora CA, Liggitt D, Koe G. Source: Radiation Research. 2001 January; 155(1 Pt 1): 2-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11121210

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Morbidity, mortality, and risk factors for esophagitis in hospital inpatients. Author(s): Newton M, Burnham WR, Kamm MA. Source: Journal of Clinical Gastroenterology. 2000 April; 30(3): 264-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10777185

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Mycobacterial esophagitis in AIDS. Author(s): Goodman P, Pinero SS, Rance RM, Mansell PW, Uribe-Botero G. Source: Gastrointest Radiol. 1989 Spring; 14(2): 103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2496001

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Naproxen induced ulcerative esophagitis. Author(s): Ecker GA, Karsh J. Source: The Journal of Rheumatology. 1992 April; 19(4): 646-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1593591

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Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Author(s): Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Source: Gastroenterology. 2003 December; 125(6): 1660-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724818

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Natural history of reflux esophagitis: what is the risk of progression and does it matter clinically? Author(s): Talley NJ. Source: Journal of Gastroenterology and Hepatology. 2002 December; 17(12): 1247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12423266

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Necrotizing esophagitis presenting as a black esophagus. Author(s): Obermeyer R, Kasirajan K, Erzurum V, Chung D. Source: Surgical Endoscopy. 1998 December; 12(12): 1430-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9822473

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Negative association between Helicobacter pylori infection and reflux esophagitis in older patients: case-control study in Japan. Author(s): Haruma K, Hamada H, Mihara M, Kamada T, Yoshihara M, Sumii K, Kajiyama G, Kawanishi M. Source: Helicobacter. 2000 March; 5(1): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10672048

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Nissen fundoplication for reflux esophagitis. Long-term clinical and endoscopic results in 109 of 127 consecutive patients. Author(s): Luostarinen M. Source: Annals of Surgery. 1993 April; 217(4): 329-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8466307

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No correlation between endoscopic and symptomatic scoring systems after the treatment of radiation esophagitis. Author(s): Koc M, Onuk MD. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 2002 February; 62(2): 243-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11937253

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No protective role of Helicobacter pylori in the pathogenesis of reflux esophagitis in patients with duodenal or benign gastric ulcer in Korea. Author(s): Kim N, Lim SH, Lee KH. Source: Digestive Diseases and Sciences. 2001 December; 46(12): 2724-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768266

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Nonobstructive dysphagia in reflux esophagitis. Author(s): Triadafilopoulos G. Source: The American Journal of Gastroenterology. 1989 June; 84(6): 614-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2729232

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NSAIDS, free radicals, and reflux esophagitis. Author(s): Morgan G. Source: Digestive Diseases and Sciences. 1996 September; 41(9): 1863. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8794807

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Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis. Author(s): Vantrappen G, Rutgeerts L, Schurmans P, Coenegrachts JL. Source: Digestive Diseases and Sciences. 1988 May; 33(5): 523-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3282846

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Omeprazole and ultrastructural modifications occurring in reflux esophagitis. Author(s): Calabrese C, Areni A, Miglioli M, DiFebo G. Source: Gastroenterology. 2002 March; 122(3): 837. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11878295

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Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group. Author(s): Hassall E, Israel D, Shepherd R, Radke M, Dalvag A, Skold B, Junghard O, Lundborg P. Source: The Journal of Pediatrics. 2000 December; 137(6): 800-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11113836

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Omeprazole or ranitidine in the treatment of reflux esophagitis. Results of a doubleblind, randomized, Scandinavian multicenter study. Author(s): Sandmark S, Carlsson R, Fausa O, Lundell L. Source: Scandinavian Journal of Gastroenterology. 1988 June; 23(5): 625-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3041558

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On-demand therapy for Los Angeles grade A and B reflux esophagitis: esomeprazole versus omeprazole. Author(s): Kao AW, Sheu BS, Sheu MJ, Chang YM, Huang SF, Chuang CH, Lai YL, Kao YH. Source: J Formos Med Assoc. 2003 September; 102(9): 607-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625604

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Open antireflux repairs for simple reflux esophagitis: short- and long-term results. Author(s): Beauchamp G, Ouellette D, Dupere S. Source: Chest Surg Clin N Am. 2001 August; 11(3): 555-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11787967

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Optimum management of mild esophagitis in Japan. Author(s): Sugano K. Source: Journal of Gastroenterology. 1999 August; 34(4): 540-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452692

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Oral administration of recombinant human granulocyte macrophage colonystimulating factor in the management of radiotherapy-induced esophagitis. Author(s): Koukourakis MI, Flordellis CS, Giatromanolaki A, Koukouraki S, Kapsoritakis A, Potamianos S, Retalis G, Sivridis E, Salsaa B, Harris AL, Maragoudakis MI. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 December; 5(12): 3970-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10632327

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Oral pantoprazole for erosive esophagitis: a placebo-controlled, randomized clinical trial. Pantoprazole US GERD Study Group. Author(s): Richter JE, Bochenek W. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3071-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11095320

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Outcome of erosive reflux esophagitis after Nissen fundoplication. Author(s): El-Serag HB, Sonnenberg A. Source: The American Journal of Gastroenterology. 1999 July; 94(7): 1771-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10406233

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Pantoprazole versus lansoprazole in French patients with reflux esophagitis. Author(s): Dupas JL, Houcke P, Samoyeau R; French Collaborative Pantaprazole Study Group. Source: Gastroenterologie Clinique Et Biologique. 2001 March; 25(3): 245-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11395670

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Pathogenesis and clinical features of eosinophilic esophagitis. Author(s): Rothenberg ME, Mishra A, Collins MH, Putnam PE. Source: The Journal of Allergy and Clinical Immunology. 2001 December; 108(6): 891-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742263

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Physiological studies on nitric oxide in the lower esophageal sphincter of patients with reflux esophagitis. Author(s): Tomita R, Tanjoh K, Fujisaki S, Fukuzawa M. Source: Hepatogastroenterology. 2003 January-February; 50(49): 110-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630004

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Pill-induced esophagitis caused by lansoprazole. Author(s): Maekawa T, Ohji G, Inoue R, Shimoyama M, Shimada T, Misaki F. Source: Journal of Gastroenterology. 2001 November; 36(11): 790-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757754

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Pill-induced esophagitis. Author(s): Misra SP, Dwivedi M. Source: Gastrointestinal Endoscopy. 2002 January; 55(1): 81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756921

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Prevalence of esophagitis in H. pylori-positive peptic ulcer disease and the impact of eradication therapy. Author(s): O'Connor HJ, McGee C, Ghabash NM, Cunnane K. Source: Hepatogastroenterology. 2001 July-August; 48(40): 1064-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490801

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Prevalence of esophagitis in patients with pH-documented laryngopharyngeal reflux. Author(s): Koufman JA, Belafsky PC, Bach KK, Daniel E, Postma GN. Source: The Laryngoscope. 2002 September; 112(9): 1606-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352672

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Prevalence of reflux esophagitis in patients with duodenal ulcer and gastric ulcer. Author(s): Amano Y, Komazawa Y, Ishimura N, Fujishiro H, Ishihara S, Adachi K, Kinoshita Y. Source: Journal of Gastroenterology. 2003; 38(5): 514-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768398

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Primary eosinophilic esophagitis. Author(s): Munitiz V, Martinez de Haro LF, Ortiz A, Pons JA, Bermejo J, Serrano A, Molina J, Parrilla P. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2003; 16(2): 165-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823222

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Pseudomembranous esophagitis. Author(s): Nayyar AK, Royston C, Slater DN, Bardhan KD. Source: Gastrointestinal Endoscopy. 2001 December; 54(6): 730-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726849

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Quality of life and cost-effectiveness of combined therapy for reflux esophagitis. Author(s): Si JM, Wang LJ, Chen SJ, Zhao L, Dai N. Source: Journal of Zhejiang University. Science. 2003 September-October; 4(5): 602-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958722

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Quality of life in patients with heartburn but without esophagitis: effects of treatment with omeprazole. Author(s): Havelund T, Lind T, Wiklund I, Glise H, Hernqvist H, Lauritsen K, Lundell L, Pedersen SA, Carlsson R, Junghard O, Stubberod A, Anker-Hansen O. Source: The American Journal of Gastroenterology. 1999 July; 94(7): 1782-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10406235

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Quantitative endoscopic classification of esophagitis by means of computerized image processing. Part 1: Theoretical background. Author(s): Manneberg G, Witt H, Slezak P. Source: Hepatogastroenterology. 1995 April; 42(2): 135-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7672762

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Quantitative endoscopic classification of esophagitis by means of computerized image processing. Part II: Experimental study. Author(s): Witt H, Manneberg G, Slezak P, Watanabe M, Kronander T. Source: Hepatogastroenterology. 1996 September-October; 43(11): 1321-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8908568

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Quinaglute-induced esophagitis mimicking an esophageal mass. Author(s): Wong RK, Kikendall JW, Dachman AH. Source: Annals of Internal Medicine. 1986 July; 105(1): 62-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3717810

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Randomized comparative study of omeprazole and famotidine in reflux esophagitis. Author(s): Kawano S, Murata H, Tsuji S, Kubo M, Tatsuta M, Iishi H, Kanda T, Sato T, Yoshihara H, Masuda E, Noguchi M, Kashio S, Ikeda M, Kaneko A. Source: Journal of Gastroenterology and Hepatology. 2002 September; 17(9): 955-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167115

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Re: Laine and Sugg-Helicobacter pylori eradication on esophagitis and GERD. Author(s): Loffeld RJ. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1201-2; Author Reply 1202-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809850

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Reduction of peptic ulcer disease and Helicobacter pylori infection but increase of reflux esophagitis in Western Sydney between 1990 and 1998. Author(s): Xia HH, Phung N, Altiparmak E, Berry A, Matheson M, Talley NJ. Source: Digestive Diseases and Sciences. 2001 December; 46(12): 2716-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768265

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Reflux complaints, symptom score and the use of medication in patients with reflux esophagitis: results of a long term follow-up study. Author(s): Loffeld RJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 August; 15(8): 505-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11544533

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Reflux esophagitis and scleroderma. Author(s): Martin J, Ferraro P, Duranceau A. Source: Chest Surg Clin N Am. 2001 August; 11(3): 619-38, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11787971

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Reflux esophagitis facilitates low Helicobacter pylori infection rate and gastric inflammation. Author(s): Jang TJ, Kim NI, Suh JI, Yang CH. Source: Journal of Gastroenterology and Hepatology. 2002 August; 17(8): 839-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164958

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Reflux esophagitis in recurrent abdominal pain. Author(s): Narula PB, Rajeshwari K, Malhotra V, Mittal SK. Source: Trop Gastroenterol. 2002 October-December; 23(4): 202-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12833714

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Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin. Author(s): Dinubile MJ, Lupinacci RJ, Berman RS, Sable CA. Source: Aids Research and Human Retroviruses. 2002 September 1; 18(13): 903-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230933

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Risk factors for the severity of erosive esophagitis in Helicobacter pylori-negative patients with gastroesophageal reflux disease. Author(s): El-Serag HB, Johanson JF. Source: Scandinavian Journal of Gastroenterology. 2002 August; 37(8): 899-904. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12229963

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Role of corpus gastritis and cagA-positive Helicobacter pylori infection in reflux esophagitis. Author(s): Queiroz DM, Rocha GA, Oliveira CA, Rocha AM, Santos A, Cabral MM, Nogueira AM. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2849-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149341

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Sarcoidosis of the esophagus presenting macroscopically as Barrett's esophagitis. Author(s): Murdock A, Jacob G. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1661-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873605

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Severe esophagitis healed in less than a week with intravenous pantoprazole. Author(s): Dabney-Smith K, Nam J, Ghazale A, Cai Q. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 78-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488715

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Severity of esophagitis in southern Indians. Author(s): Jayanthi V. Source: Indian J Gastroenterol. 2002 September-October; 21(5): 205. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416759

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Significance of duodenogastric reflux in patients with erosive esophagitis. Author(s): Simic A, Pesko P. Source: Acta Chir Iugosl. 2000; 47(3): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11432229

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Subglottic stenosis complicated by allergic esophagitis: case report. Author(s): Hartnick CJ, Liu JH, Cotton RT, Rudolph C. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 January; 111(1): 5760. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11800370

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Sucralfate in the treatment of reflux esophagitis in adults: an update. Author(s): Simon B, Dammann HG, Muller P. Source: Scandinavian Journal of Gastroenterology. Supplement. 1989; 156: 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2662389

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Sucralfate in the treatment of reflux esophagitis in children. Preliminary results. Author(s): Arguelles-Martin F, Gonzalez-Fernandez F, Gentles MG, Navarro-Merino M. Source: Scandinavian Journal of Gastroenterology. Supplement. 1989; 156: 43-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2740841

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Superoxide anion and nitric oxide in high-grade esophagitis induced by acid and pepsin in rabbits. Author(s): Lanas A, Soteras F, Jimenez P, Fiteni I, Piazuelo E, Royo Y, Ortego J, Inarrea P, Esteva F. Source: Digestive Diseases and Sciences. 2001 December; 46(12): 2733-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768267

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Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease. Author(s): Armstrong D, Pare P, Pericak D, Pyzyk M; Canadian Pantoprazole GERD Study Group. Source: The American Journal of Gastroenterology. 2001 October; 96(10): 2849-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11695354

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Symptom relief in patients with reflux esophagitis: comparative study of omeprazole, lansoprazole, and rabeprazole. Author(s): Adachi K, Hashimoto T, Hamamoto N, Hirakawa K, Niigaki M, Miyake T, Taniura H, Ono M, Kaji T, Suetsugu H, Yagi J, Komazawa Y, Mihara T, Katsube T, Fujishiro H, Shizuku T, Hattori S, Yamamoto S, Kinoshita Y. Source: Journal of Gastroenterology and Hepatology. 2003 December; 18(12): 1392-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675268

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Tetracycline-induced spongiotic esophagitis: a new endoscopic and histopathologic finding. Author(s): Banisaeed N, Truding RM, Chang CH. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 292-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872108

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The association between CagA status and the development of esophagitis after the eradication of Helicobacter pylori. Author(s): Rokkas T, Ladas SD, Triantafyllou K, Liatsos C, Petridou E, Papatheodorou G, Karameris A, Raptis SA. Source: The American Journal of Medicine. 2001 June 15; 110(9): 703-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11403754

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The clinical and histological spectrum of esophagitis in pediatrics. Some keys to its links to gastritis. Author(s): Cohen MC, Rua R, Balcarce N, Drut R. Source: Acta Gastroenterol Latinoam. 2001; 31(3): 143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11577566

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The effect of eight weeks of rabeprazole therapy on nitric oxide plasma level and esophageal pH and motility and motility nitric oxide plasma level in patients with erosive esophagitis. Author(s): Swiatkowski M, Budzynski J, Klopocka M, Grad K, Pulkowski G, Augustynska B, Suppan K, Fabisiak J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2004 February; 10(2): Cr46-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14737042

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The natural history of dysplasia and cancer in esophagitis and Barrett esophagus. Author(s): Spechler SJ. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5 Suppl): S2-5; Discussion S26-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702959

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The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. Author(s): Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. Source: The Journal of Allergy and Clinical Immunology. 2002 February; 109(2): 363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11842310

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Therapeutic effect of oral recombinant human granulocyte macrophage-colony stimulating factor in radiotherapy-induced esophagitis. Author(s): Koc M, Onuk MD, Koruk M, Memik F. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571722

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Topical corticosteroid treatment of dysphagia due to eosinophilic esophagitis in adults. Author(s): Arora AS, Perrault J, Smyrk TC. Source: Mayo Clinic Proceedings. 2003 July; 78(7): 830-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839078

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Treatment of esophagitis/vagitis-induced paroxysmal atrial fibrillation by protonpump inhibitors. Author(s): Stollberger C, Finsterer J. Source: Journal of Gastroenterology. 2003; 38(11): 1109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673734

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Ulcerative colitis and cytomegaloviral esophagitis: two diseases, two randomized, controlled trials. Author(s): Surawicz CM. Source: Current Gastroenterology Reports. 1999 August; 1(4): 280-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980961

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Ulcerative esophagitis caused by etidronate. Author(s): Macedo G, Azevedo F, Ribeiro T. Source: Gastrointestinal Endoscopy. 2001 February; 53(2): 250-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11174310

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Ulcerative esophagitis during primary HIV infection. Author(s): Ruiz-Laiglesia FJ, Torrubia-Perez CB, Perez-Calvo JI. Source: Archives of Internal Medicine. 1996 May 27; 156(10): 1115. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8639003

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Ulcerative esophagitis during primary HIV infection. Author(s): Fusade T, Liony C, Joly P, Paoletti C, Metayer J, Lauret P. Source: The American Journal of Gastroenterology. 1992 October; 87(10): 1523-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1415118

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Ulcerative esophagitis in Behcet's syndrome. Author(s): Anti M, Marra G, Rapaccini GL, Fedeli G. Source: Gastrointestinal Endoscopy. 1985 August; 31(4): 289. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4029581

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Ulcerative esophagitis. A rare source of upper gastrointestinal bleeding in a neonate. Use of fiberoptic endoscopy for diagnosis. Author(s): Borowitz SM. Source: Clinical Pediatrics. 1989 February; 28(2): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2914415

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Upper esophageal sphincter spasm as a marker of monilial esophagitis. Author(s): Graham JR. Source: Gastrointestinal Endoscopy. 1990 January-February; 36(1): 77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2311894

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Upper gastrointestinal tract bleeding in institutionalized mentally retarded adults. Primary role of esophagitis. Author(s): Orchard JL, Stramat J, Wolfgang M, Trimpey A. Source: Archives of Family Medicine. 1995 January; 4(1): 30-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7812473

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Upright refluxers without esophagitis differentiated from bipositional refluxers with esophagitis by simultaneous manometry and pH monitoring conducted in two postures before and after a meal. Author(s): Shay SS, Johnson LF. Source: The American Journal of Gastroenterology. 1994 July; 89(7): 992-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8017397

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Using non-invasive radionuclide imaging to detect esophagitis in patients with gastroesophageal reflux disease. Author(s): Hsu CH, Shiun SC, Hsu NY, Sun SS, Kao A, Lee CC, Lin CC. Source: Hepatogastroenterology. 2003 January-February; 50(49): 107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630003

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Value of radiology in the diagnosis of reflux esophagitis. Author(s): Derksen OS, Booy AP, van de Borne H, Kho SN, van Rhijn TC. Source: Diagn Imaging Clin Med. 1985; 54(5): 257-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3850012

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Variability in the clinical presentation and endoscopic findings of herpetic esophagitis. Author(s): Byard RW, Champion MC, Orizaga M. Source: Endoscopy. 1987 July; 19(4): 153-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3622396

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Vascular changes in the esophageal mucosa. An early histologic sign of esophagitis. Author(s): Geboes K, Desmet V, Vantrappen G, Mebis J. Source: Gastrointestinal Endoscopy. 1980 May; 26(2): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7390102

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Vertical lines in distal esophageal mucosa (VLEM): a true endoscopic manifestation of esophagitis in children? Author(s): Gupta SK, Fitzgerald JF, Chong SK, Croffie JM, Collins MH. Source: Gastrointestinal Endoscopy. 1997 June; 45(6): 485-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9199905

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Viral esophagitis: the endoscopic appearance. Author(s): Kadakia SC. Source: Gastrointestinal Endoscopy. 1992 September-October; 38(5): 633-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1327939

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What are the roles of eosinophils in esophagitis? Author(s): Sondheimer JM. Source: Journal of Pediatric Gastroenterology and Nutrition. 1998 July; 27(1): 118-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9669741

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When is esophagitis healed? esophageal endoscopy, histology and function before and after cimetidine treatment. Author(s): Sonnenberg A, Lepsien G, Muller-Lissner SA, Koelz HR, Siewert JR, Blum AL. Source: Digestive Diseases and Sciences. 1982 April; 27(4): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7067581

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Why does sucralfate improve healing in reflux esophagitis? The role of sucrose octasulfate. Author(s): Orlando RC, Tobey NA. Source: Scandinavian Journal of Gastroenterology. Supplement. 1990; 173: 17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2349455

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Why is the high grade inhibition of gastric acid secretion afforded by proton pump inhibitors often required for healing of reflux esophagitis? An epithelial perspective. Author(s): Orlando RC. Source: The American Journal of Gastroenterology. 1996 September; 91(9): 1692-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792683

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Zollinger-Ellison syndrome presenting as reflux esophagitis and stricture. Author(s): Ramakrishnan T. Source: J La State Med Soc. 1981 December; 133(12): 189-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7343631

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Zollinger-Ellison syndrome with esophagitis and Barrett mucosa. Author(s): Karl TR, Pindyck F, Sicular A. Source: The American Journal of Gastroenterology. 1983 October; 78(10): 611-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6624733

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

Finding Nutrition Studies on Esophagitis 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.4 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 “esophagitis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

4 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 “esophagitis” (or a synonym): •

Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of reflux esophagitis and the influence of Helicobacter pylori infection on healing rate. Author(s): Division of Gastroenterology, Department of Medicine, Medical School of Ribeirao Preto, Brazil. [email protected] Source: Meneghelli, U G Boaventura, S Moraes Filho, J P Leitao, O Ferrari, A P Almeida, J R Magalhaes, A F Castro, L P Haddad, M T Tolentino, M Jorge, J L Silva, E Maguilnik, I Fischer, R Dis-Esophagus. 2002; 15(1): 50-6 1120-8694

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Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Author(s): Pediatric Gastroenterology and Nutrition, Department of Pathology, and Division of Allergy and Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Source: Teitelbaum, Jonathan E Fox, Victor L Twarog, Frank J Nurko, Samuel Antonioli, Don Gleich, Gerald Badizadegan, Kamran Furuta, Glenn T Gastroenterology. 2002 May; 122(5): 1216-25 0016-5085

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Herpes simplex esophagitis in immunocompetent individuals. Author(s): Department of Medicine, P D Hinduja National Hospital and Medical Research Center, Mumbai. Source: Ashar Sampat, U Desai, D Bhaduri, A Joshi, A Udwadia, Z F Indian-JGastroenterol. 2001 Nov-December; 20(6): 245-6 0254-8860

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Pill-induced esophagitis caused by oral rifampin. Author(s): School of Pharmacy, University of the Pacific, Stockton, CA, USA. Source: Smith, S J Lee, A J Maddix, D S Chow, A W Ann-Pharmacother. 1999 January; 33(1): 27-31 1060-0280

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND ESOPHAGITIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to esophagitis. At the conclusion of this chapter, we will provide additional sources.

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

“Total” therapy for oat cell carcinoma of the lung. Author(s): Kent CH, Brereton HD, Johnson RE. Source: International Journal of Radiation Oncology, Biology, Physics. 1977 May-June; 2(5-6): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=195919

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Comparison of IY81149 with omeprazole in rat reflux oesophagitis. Author(s): Kil BJ, Kim IW, Shin CY, Jeong JH, Jun CH, Lee SM, Kim DY, Huh IH, Sohn UD. Source: Journal of Autonomic Pharmacology. 2000 October-December; 20(5-6): 291-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11350494

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Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy.

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Author(s): Hirota S, Tsujino K, Endo M, Kotani Y, Satouchi M, Kado T, Hishikawa Y, Obayashi K, Takada Y, Kono M, Abe M. Source: International Journal of Radiation Oncology, Biology, Physics. 2001 October 1; 51(2): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11567801 •

Effects of rutin and harmaline on rat reflux oesophagitis. Author(s): Shin YK, Sohn UD, Choi MS, Kum C, Sim SS, Lee MY. Source: Autonomic & Autacoid Pharmacology. 2002 February; 22(1): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12423426

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Efficacy of a pectin-based anti-reflux agent on acid reflux and recurrence of symptoms and oesophagitis in gastro-oesophageal reflux disease. Author(s): Havelund T, Aalykke C, Rasmussen L. Source: European Journal of Gastroenterology & Hepatology. 1997 May; 9(5): 509-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9187886

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Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features. Author(s): Potter JW, Saeian K, Staff D, Massey BT, Komorowski RA, Shaker R, Hogan WJ. Source: Gastrointestinal Endoscopy. 2004 March; 59(3): 355-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997131

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Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer. Author(s): Choy H, LaPorte K, Knill-Selby E, Mohr P, Shyr Y. Source: Seminars in Radiation Oncology. 1999 April; 9(2 Suppl 1): 90-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210546

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Lozenge-induced esophagitis. Author(s): Sharara AI. Source: Gastrointestinal Endoscopy. 2000 May; 51(5): 622-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10805861

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Multiple esophageal rings: an association with eosinophilic esophagitis: case report and review of the literature. Author(s): Siafakas CG, Ryan CK, Brown MR, Miller TL. Source: The American Journal of Gastroenterology. 2000 June; 95(6): 1572-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894599

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Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants in its treatment.

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Author(s): Oh TY, Lee JS, Ahn BO, Cho H, Kim WB, Kim YB, Surh YJ, Cho SW, Hahm KB. Source: Free Radical Biology & Medicine. 2001 April 15; 30(8): 905-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295533 •

Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats. Author(s): Oh TY, Lee JS, Ahn BO, Cho H, Kim WB, Kim YB, Surh YJ, Cho SW, Lee KM, Hahm KB. Source: Gut. 2001 September; 49(3): 364-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511558

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Personal experience in TCM treatment of reflux esophagitis. Author(s): Hong L. Source: J Tradit Chin Med. 2003 September; 23(3): 175-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535176

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Postprandial hypoglycemia after Nissen fundoplication for reflux esophagitis. Author(s): Zaloga GP, Chernow B. Source: Gastroenterology. 1983 April; 84(4): 840-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6825995

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Ranitidine and high-dose antacid in reflux oesophagitis. A randomized, placebocontrolled trial. Author(s): Grove O, Bekker C, Jeppe-Hansen MG, Karstoft E, Sanchez G, Axelsson CK, Nielsen HO, Andersen B, Rask-Madsen J. Source: Scandinavian Journal of Gastroenterology. 1985 May; 20(4): 457-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3895381

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The small-caliber esophagus: an unappreciated cause of dysphagia for solids in patients with eosinophilic esophagitis. Author(s): Vasilopoulos S, Murphy P, Auerbach A, Massey BT, Shaker R, Stewart E, Komorowski RA, Hogan WJ. Source: Gastrointestinal Endoscopy. 2002 January; 55(1): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756928

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The use of hypnosis in the treatment of reflux esophagitis: a case report. Author(s): Zlotogorski Z, Anixter WL. Source: Am J Clin Hypn. 1983 April; 25(4): 232-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6673580

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

General Overview Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Colic Source: Healthnotes, Inc.; www.healthnotes.com Gastroesophageal Reflux Disease Source: Healthnotes, Inc.; www.healthnotes.com Gastroesophageal Reflux Disease Source: Integrative Medicine Communications; www.drkoop.com Heartburn Source: Integrative Medicine Communications; www.drkoop.com Leukoplakia Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Aluminum Hydroxide Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lansoprazole Source: Healthnotes, Inc.; www.healthnotes.com Omeprazole Source: Healthnotes, Inc.; www.healthnotes.com Ranitidine Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. PATENTS ON ESOPHAGITIS 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.5 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 “esophagitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on esophagitis, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Esophagitis By performing a patent search focusing on esophagitis, 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 5Adapted

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 esophagitis: •

Antacid composition Inventor(s): Buehler; John D. (Germantown, PA), Grim; Wayne M. (Doylestown, PA), Luber; Joseph R. (Lafayette Hills, PA) Assignee(s): Rorer Pharmaceutical Corporation (Fort Washington, PA) Patent Number: 4,869,902 Date filed: May 9, 1988 Abstract: A pharmaceutical composition including magnesium alginate and an antacid material useful in the treatment of reflux esophagitis. Excerpt(s): The present invention relates to pharmaceutical compositions and particularly to compositions for use in treating gastroesophageal and gastrointestinal irritations. Esophageal pain, commonly experienced as heartburn, is symptomatic of gastric reflux. Gastric reflux occurs when small amounts of gastric juice and/or bile acids pass into the lower part of the esophagus and cause esophageal irritation. Typically, gastric reflux, which occurs after meals, especially large meals, is aggravated by bending over or lying down, and is a common occurence in patients having a hiatal hernia, or a weakening of the esophageal sphincter. Severe episodes of gastric reflux may inflame the esophageal mucosa and lead to the more serious condition of reflux esophagitis in which severe damage or loss of squamous epithelium of the lower part of the esophagus may occur. If esophagitis is persistent or severe, an inflammatory blockage of the esophagus may develop. The invention relates to a composition useful in the treatment of reflux esophagitis. Web site: http://www.delphion.com/details?pn=US04869902__

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Bed angle-elevators Inventor(s): Styblo; Norbert (33 Tremont St., Carver, MA 02330) Assignee(s): none reported Patent Number: 5,199,122 Date filed: April 8, 1992 Abstract: An extension or elevator device for the legs supporting bed-frames of various design, which are arranged to raise the head of the bed. The resultant pitching of the sleeping surface is to reduce stomach acid reflux into the esophagus in the condition Reflux Esophagitis (commonly: heartburn) during bedrest. Device is installed in place of casters or gliders, and has provision for replacing casters in order to retain the original floor-bearing and mobility characteristics of the bed. Excerpt(s): The present invention relates to beds, specifically to devices which may be applied to the legs of bedframes for the purpose of extension, in a configuration resulting in the angling of the sleeping-surface. Reflux Esophagitis (commonly: heartburn) is a painful medical condition typically caused by the reflux of stomach acid into the esophagus. Discomfort can be acute and persistent, particularly to people suffering from a hiatus hernia. Due to the relative position of stomach and esophagus, lying flat in bed usually increases the likelihood of acid reflux, and the discomfort it

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causes. A common solution recommended by the medical profession for pain relief during bedrest is to elevate the head of the patient's bed four or five inches (10 or 12.7 cm.), thereby angling the sleeping surface to physically prevent acid reflux. Usually this is followed by a suggestion for the patient to improvise some sort of blocking under the bed legs of appropriate height to accomplish this end. While a simple and effective solution, this method can be unstable, can cause damage to floor finishes, and negates the usefulness of casters or gliders for facilitating bed mobility. Web site: http://www.delphion.com/details?pn=US05199122__ •

Dosage forms of risedronate Inventor(s): Axelrod; Douglas W. (Norwich, NY), Dansereau; Richard J. (Sherburne, NY), Mosher; Russell Y. (Norwich, NY), Sietsema; William K. (Norwich, NY) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 5,622,721 Date filed: September 14, 1994 Abstract: The present invention is directed to a novel enteric-coated oral dosage form of a risedronate active ingredient comprised of a safe and effective amount of a pharmaceutical composition which is comprised of a risedronate active ingredient and pharmaceutically-acceptable excipients. Said dosage forms prohibit the exposure of the risedronate active ingredient to the epithelial and mucosal tissues of the buccal cavity, pharynx, esophagus, and stomach and thereby protects said tissues from erosion, ulceration or other like irritation. Accordingly, the said dosage forms effect the delivery to the lower gastrointestinal tract of said human or other mammal of a safe and effective amount of the risedronate active ingredient, and substantially alleviate the esophagitis or esophageal irritation which occasionally accompanies the oral administration of risedronate active ingredients. Excerpt(s): The present invention relates to novel oral dosage forms of the diphosphonate compound, 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid, hereinafter referred to as "risedronate". Said novel dosage forms are enteric-coated and delay the release of the risedronate until the lower gastrointestinal tract is reached, thereby protecting the epithelial and mucosal tissues of the mouth and the buccal cavity, the pharynx, the larynx, and the esophagus from erosion, ulceration, or other like irritation suffered by direct contact of these tissues with the risedronate active ingredient which may sometimes result from the oral administration of risedronate. This invention further relates to a method of treating or preventing diseases characterized by abnormal calcium and phosphate metabolism using the novel enteric coated dosage forms described herein. 1. Conditions which are characterized by anomalous mobilization of calcium and phosphate leading to general or specific bone loss or excessively high calcium and phosphate levels in the fluids of the body. Such conditions are sometimes referred to herein as patholological hard tissue demineralizations. 2. Conditions which cause or result from deposition of calcium and phosphate anomalously in the body. These conditions are sometimes referred to herein as pathological calcifications. Web site: http://www.delphion.com/details?pn=US05622721__

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Method for testing for esophagitis Inventor(s): Angelchik; Jean P. (522 W. Northview, Phoenix, AZ 85021) Assignee(s): none reported Patent Number: 5,381,800 Date filed: March 12, 1992 Abstract: A method and apparatus for administering a test to detect the esophagitis in a patient utilizes a sealed pliable tube. When the tube is unsealed and inserted in the esophagus of a patient, an acidic solution stored in the tube flows into the esophagus and, if the patient has esophagitis, causes the chest pain or other symptoms which the patient experiences during esophagitis. Excerpt(s): This invention relates to a method and apparatus for diagnosing esophagitis in a patient. More particularly, the invention relates to portable apparatus of inexpensive manufacture which can quickly and easily be utilized in a hospital emergency room, in a physician's office, or at the residence of a patient to determine whether chest pains experienced by the patient are, instead of being caused by a heart condition, caused by esophagitis. In another respect, the invention relates to esophagitis test apparatus which administers a test fluid to a patient under atmospheric pressure and the force of gravity and utilizes displacement pressures generated by peristaltic motion to assist in the distribution of the fluid in the esophagus of a patient. Web site: http://www.delphion.com/details?pn=US05381800__

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Method of treatment of gastroesophageal reflux disease by enhancement of salivary esophageal protection due to mastication Inventor(s): McCallum; Richard (Charlottesville, VA), Sarosiek; Jerzy (Charlottesville, VA) Assignee(s): The University of Virginia Patents Foundation (Charlottesville, VA) Patent Number: 5,730,958 Date filed: August 16, 1996 Abstract: Prolonged mastication is demonstrated to enhance salivary secretion as well as enhance secretion of salivary components such as salivary bicarbonate, epidermal growth factor, mucin, PGE.sub.2 and transforming growth factor.sub.alpha. Mastication beginning prior to about 30 minutes in advance of any meal may reduce sensations of heartburn in patients and has therapeutic value in the treatment of patients with reflux esophagitis and gastroesophageal reflux disease. Post-meal chewing is of additional value in alleviating severe symptoms. Excerpt(s): This application claims priority of U.S. Provisional application Ser. 60/002,511, filed Aug. 18, 1995. This invention pertains to a method of treating gastroesophageal reflux disease (GERD) by encouraging patients suffering from the same to chew, or masticate. Mastication, both pre- and post-meal chewing, improves esophageal protection, useful in treating and controlling GERD. Those who suffer from endoscopic RE may also benefit from such mastication, as an augment to other available therapies. The item chewed may be any non-toxic chewable item that will support an extended period (at least about 30 minutes) of chewing, including conventional chewing gums, inert plastic films, leather and the like. The protective role of salivary inorganic and organic components in the maintenance of the esophageal mucosal integrity both in

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the experimental and clinical settings is a rapidly evolving research arena. It has been demonstrated experimentally that surgical removal of salivary glands in rats resulted in 108% increase in the rate of permeability of the esophageal mucosa to hydrogen ion accompanied by an 83% decline in the content of mucus within the pre-epithelial mucosal barrier. Sarosiek et al., Am. J. Med. Sci. 302:359-363 (1991). Clinical studies have revealed that salivary buffering capacity is pivotal in restoration of pH within the preepithelial barrier as assessed by 24 hour pH monitoring. Helm et al., Gastroenterology 83:69-74(1982). In addition, a plethora of salivary organic components such as epidermal growth factor (EGF), mucin, PGE.sub.2 and transforming growth factor.sub.alpha. (TGF.sub.alpha.) well known for their protective potential within the oral cavity and gastric mucosa, are shown to have a significant impact on the integrity of the esophageal mucosal barrier. Therefore, a quantitative and qualitative enhancement of salivary secretion that could benefit protective mechanisms operating within the esophageal preepithelial barrier, crucial in the combat of gastroesophageal reflux (GER) is an object of these of skill in the art. Web site: http://www.delphion.com/details?pn=US05730958__ •

Protection of the esophagus from chemotherapeutic or irradiation damage by gene therapy Inventor(s): Greenberger; Joel S. (Sewickley, PA) Assignee(s): University of Pittsburgh (Pittsburgh, PA) Patent Number: 6,221,848 Date filed: May 11, 1998 Abstract: A method of protecting a subject against an agent that elicits production of toxic free radicals, superoxide anions, or heavy metal cations in the subject is disclosed which entails in vivo administration to the subject of a polynucleotide encoding a protein that is transiently expressed in said subject. The transiently expressed protein is capable of neutralizing or eliminating the toxic free radicals, superoxide anions or heavy metal cations that are elicited by the agent. The method is particularly useful in preventing the development of esophagitis during treatment of lung cancer patients with ionizing radiation and/or chemotherapeutic drugs. Excerpt(s): The present invention is directed generally to protecting an individual's tissues and cells against the damaging effects of an agent that elicits the production of a free radical, superoxide anion, or heavy metal cation when that individual is exposed to the agent. Specifically, the invention is directed to protection of the oral cavity, oropharynx, esophagus, stomach, small intestine and colon by transient expression of a protective protein through somatic gene transfer in vivo. Therapeutic concentrations of anti-cancer drugs and clinical radiation therapy are known to damage a patient's normal tissues and cells. A need clearly exists for means to protect a patient's normal tissues during chemotherapy and/or radiation therapy. Previous methods of affording such protection include administration of sulfhydryl compounds such as thiols or other radical scavenger compounds. The major way in which radiation damages biomolecules and cells is through its interaction with water to produce toxic free radicals (H.circlesolid., OH.circle-solid., e.sub.aq.sup.-) and H.sub.2 O.sub.2 or, through interaction with oxygen, to produce the superoxide radicals (.ANG.O.sub.2.sup.-). In the late 1940's it was discovered that sulfhydryl compounds, such as cysteine and cysteamine, provide radiation protection in animals. Patt et al., Science 110: 213 (1949). Thiol groups scavenge radiation-produced free radicals by donating a hydrogen atom to damaged molecules.

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Despite extensive efforts to develop more effective protective agents, no thiol-based radioprotector has been found to be significantly better than cysteamine. Mitchell et al., Arch. Biochem. and Biophys. 289: 62 (1991). However, the use of thiol drugs to protect against radiation damage is limited by the toxicity of such compounds. Web site: http://www.delphion.com/details?pn=US06221848__ •

Sucralfate preparations Inventor(s): Kashimura; Koji (Tokyo, JP), Ozawa; Koichi (Tokyo, JP) Assignee(s): Chugai Seiyaku Kabushiki Kaisha (Tokyo, JP) Patent Number: 5,968,906 Date filed: August 4, 1997 Abstract: Sucralfate containing preparations which contain both an organic acid having at least two carboxyl groups or at least one carboxyl group in the molecule and sucralfate are described. The sucralfate containing preparations have enhanced sucralfate adhesion to the mucosal ulcer site even under a nonacidic condition and can be extensively applied not only to ulcers in the upper digestive tract such as esophagitis and duodenal ulcer but also to ulcers in the lower digestive tract such as proctitis and ulcerative colitis, as well as to dermal ulcers such as bedsores, stomatitis and the like. Excerpt(s): This invention relates to sucralfate containing preparations that can be applied to mucosal damage and the like in a nonacidic condition and, more particularly, it relates to sucralfate preparations containing both an organic carboxylic acid having at least two carboxyl groups or at least one hydroxyl group in the molecule and sucralfate. Sucralfate is a medicine that is described in the Japanese Pharmacopoeia and commonly used as a therapeutic for gastric and duodenal ulcers. The mechanism of its action is known to be attributable to antipepsin and antacid effects and the like. Two principal effects of sucralfate are believed to be forming a highly adhesive gel under an acidic condition to cover an ulcerated surface and in binding with plasma proteins under an acidic condition to cover the ulcerated surface (i.e., a mucosa protecting action). However, for selective binding to the mucosal ulcer site, the formation of a gel under the acidic condition caused by gastric acid is essential and in areas where acids are absent such as the small intestine, colon and the skin, no chemical binding and adhesion to the ulcer site occurs, except by physical adsorption. There have been very few cases of the application of sucralfate which has been provided with enhanced adhesion to mucous membranes as in the small intestine and colon and the only exception is found in Japanese Patent Public Disclosure No. 190127/1987, which describes the application of added, collagen to the wound site. In known cases of sucralfate application to ulcerative colitis, sucralfate suspensions prepared with methylcellulose, propylcellulose and the like being added as thickeners are administered by the enteral route (see Scand. J. Gastroenterol., vol. 24, pp. 1014, 1989, Endoscopy, vol. 18, pp. 115, 1986, etc.) but these preparations have encountered several problems, one of which is that adhesion to the ulcer site is not expected. Web site: http://www.delphion.com/details?pn=US05968906__

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Patent Applications on Esophagitis As of December 2000, U.S. patent applications are open to public viewing.6 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 esophagitis: •

Novel dosage forms of risedronate Inventor(s): Axelrod, Douglas Wayne; (Milford, OH), Dansereau, Richard John; (Cincinnati, OH), Mosher, Russell James; (Binghamton, NY), Sietsema, William Kendall; (West Chester, OH) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20040037884 Date filed: June 6, 2003 Abstract: The present invention is directed to a novel enteric-coated oral dosage form of a risedronate active ingredient comprised of a safe and effective amount of a pharmaceutical compostion which is comprised of a risedronate active ingredient and pharmaceutically-acceptable excipients. Said dosage forms prohibit the exposure of the risedronate active ingredient to the epithelial and mucosal tissues of the buccal cavity, pharynx, esophagus, and stomach and thereby protects said tissues from erosion, ulceration or other like irritation. Accordingly, the said dosage forms effect the delivery to the lower intestinal tract of said human or other mammal of a safe and effective amount of the risedronate active ingredient, and substantially alleviate the esophagitis or esophageal irritation which sometimes accompanies the oral administration of risedronate active ingredients. Excerpt(s): The present invention relates to novel oral dosage forms of the diphosphonate compound, 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid, hereinafter referred to as "risedronate". Said novel dosage forms are enteric-coated and delay the release of the risedronate until the lower intestinal tract is reached, thereby protecting the epithelial and mucosal tissues of the mouth and the buccal cavity, the pharynx, the larynx, and the esophagus from erosion, ulceration, or other like irritation suffered by direct contact of these tissues with the risedronate active ingredient which may sometimes result from the oral administration of risedronate. This invention further relates to a method of treating or preventing diseases characterized by abnormal calcium and phosphate metabolism using the novel enteric coated dosage forms described herein. 1. Conditions which are characterized by anomalous mobilization of calcium and phosphate leading to general or specific bone loss or excessively high calcium and phosphate levels in the fluids of the body. Such conditions are sometimes referred to herein as pathological hard tissue demineralizations. The compound risedronate is a more biologically potent diphosphonate compound which can be administered at low dosage levels; these lower dosage levels have resulted in a wider margin of safety and cause little or no mineralization inhibition. It is believed that the decrease in the inhibition of bone mineralization which is exhibited by the low dosage levels occurs because mineralization inhibition is predominately a mass related physiochemical effect, whereas resorption inhibition results from a biological interaction

6

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

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with the cells. In addition, low dosage levels are also desirable to avoid the gastrointestinal discomfort, like nausea, diarrhea, and abdominal pains, which are sometimes associated with the oral administration of disphosphonates. 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 esophagitis, 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 “esophagitis” (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 esophagitis. You can also use this procedure to view pending patent applications concerning esophagitis. 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 ESOPHAGITIS Overview This chapter provides bibliographic book references relating to esophagitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on esophagitis 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 “esophagitis” (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 esophagitis: •

Gastroesophageal Reflux Disease Source: Monticello, NY: Marcel Dekker, Inc. 2000. 405 p. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701-5185. (800) 228-1160 or (212) 696-9000. Fax (845) 796-1772. E-mail: [email protected]. Website: www.dekker.com. PRICE: $175.00 plus shipping and handling. Summary: Common and complex, gastroesophageal reflux disease (GERD) has seen an explosion in interest from both lay and scientific communities. The editor of this text notes that GERD symptoms and signs can masquerade innocently as heartburn, yet this condition can lead to esophageal tissue destruction, Barrett's esophagus, and esophageal adenocarcinoma, a deadly cancer whose frequency has increased dramatically in recent decades. This text on GERD offers twelve chapters, each written by experts in the field, covering: clinical manifestations, natural history and differential diagnosis of reflux esophagitis; the risk factors for GERD; epidemiology of GERD; diagnostic tests for

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GERD; the pathophysiology of GERD, notably the antireflux barrier and luminal clearance mechanisms; the role of offensive factors and tissue resistance in the pathophysiology of GERD; esophageal complications of GERD (other than Barrett's esophagus); Barrett's esophagus; extraesophageal complications of GERD; the medical therapy of GERD; the surgical treatment of GERD; and GERD in infants and children. Each chapter includes extensive references and is illustrated with black and white reproductions of endoscopic photographs. The text concludes with a detailed subject index. •

Esophagus and Stomach Source: Orlando, FL: Mosby, Inc. 2003. 200 p. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $89.95. ISBN: 323018866. Summary: In this textbook, established experts cover all of the essential information on the esophagus and stomach. The book offers thirteen chapters: gastroesophageal reflux disease; other causes of esophagitis; Barrett's esophagus; esophageal motility disorders; transfer dysphagia; rings, webs, stenoses, and diverticula of the esophagus; esophageal cancer; Helicobacter pylori gastritis and other gastric infections; peptic ulcer disease; gastroparesis and other gastric motor abnormalities; non-ulcer dyspepsia; foreign bodies of the upper gastrointestinal tract; and gastric cancer, lymphoma, and carcinoids of the stomach. The authors focus on differential diagnosis, pitfalls, and evidence-based management approaches. Each chapter begins with a chapter outline, includes extensive tables and illustrations, and concludes with a list of recommended readings. A subject index concludes the volume.

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Gastroenterology and Hepatology: The Comprehensive Visual Reference. Volume 5: Esophagus and Pharynx Source: Philadelphia, PA: Current Medicine. 1997. [200 p.]. Contact: Available from Current Medicine. 400 Market Street, Suite 700, Philadelphia, PA 19106. (800) 427-1796 or (215) 574-2266. Fax (215) 574-2270. E-mail: [email protected]. Website: current-medicine.com. PRICE: $125.00 plus shipping and handling. ISBN: 0443078556. Summary: This atlas is one in an 8-volume collection of images that pictorially displays the gastrointestinal tract, liver, biliary tree, and pancreas in health and disease, both in children and adults. This volume includes 11 chapters on the esophagus and pharynx, each written by experts in their respective fields. The esophagus is a long, tubular organ designed to actively transmit ingested material from mouth to stomach. When diseased, organ dysfunction becomes clinically manifest by symptoms of dysphagia, chest pain, heartburn, or regurgitation. The chapters cover the esophagus in both health and disease. Beginning with a chapter on esophageal anatomy and physiology, the volume covers the role of endoscopy and manometry, pH monitoring, and Bernstein testing in patient assessment, as well as gastroesophageal reflux disease, acute esophagitis, esophageal motor disorders, the pharynx, esophageal tumors, noncardiac chest pain, therapeutic endoscopy, and surgery of the esophagus. The format of the atlas is visual images supported by relatively brief text. Tables, charts, diagrams, and photomicrographs are used extensively.

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Ulcer Story: The Authoritative Guide to Ulcers, Dyspepsia, and Heartburn Source: New York, NY: Plenum Publishing. 1996. 415 p. Contact: Available from Plenum Publishing. 233 Spring Street, New York, NY 110131578. (800) 221-9369 or (212) 620-8000. PRICE: $29.95. ISBN: 0306452758. Summary: This book brings the general reader up to date on the causes and treatments of ulcers, dyspepsia, and heartburn. The book is divided into seven parts. The first begins with a review of upper gut anatomy; chapters on physiology and terminology are designed to assist those with a nonmedical background. Technical terms and short forms are redefined at the beginnings of relevant chapters. Next is a brief history of peptic ulcer and gastroesophageal reflux. Part One ends with a discussion of the epidemiology of ulcers, dyspepsia, and heartburn. Part Two discusses the causes of peptic ulcer. The anti-arthritis NSAIDs and infection of the gastric mucosa with Helicobacter pylori are the principal causes of peptic ulcers. Part Three discusses dyspepsia, the cardinal symptom of ulcers. A brief description of gastric and duodenal ulcers, a review of rare and atypical ulcers, and a discussion of ulcer complications follow the discussion of dyspepsia. Part Four focuses on gastroesophageal reflux (GER), the mechanism underlying heartburn and esophagitis. The author notes that heartburn is often confused with dyspepsia, both ulcers and esophagitis depend upon gastric acid, and both diseases are healed with anti-ulcer drugs. Part Five addresses related subjects, including non-ulcer dyspepsia, abdominal bloating, noncardiac chest pain, and gastric and esophageal cancers. In Part Six, the author reviews the drugs prescribed and operations performed for peptic ulcers or gastroesophageal reflux disease. Part Seven focuses on diagnostic tests and research activities that support the treatment options for ulcer, heartburn, dyspepsia, and other symptoms. The author offers a British perspective on health care. A subject index concludes the volume. 397 references. (AA-M).

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Indigestion: Living Better with Upper Intestinal Problems from Heartburn to Ulcers and Gallstones Source: New York, NY: Oxford University Press. 1992. 227 p. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $11.95 plus shipping and handling. ISBN: 019508554X. Summary: This book offers advice on how to take care of and avoid a whole complex of disturbances categorized as indigestion. The author begins with an overview of the anatomy and physiology of digestion, including a chapter on terminology and definitions. After an additional chapter on diagnostic testing, the author turns to specific problems, including acid related problems (heartburn, esophagitis, and hiatal hernia), peptic ulcers, nonulcer dyspepsia, chest pain, gallbladder problems and gallstones, pancreatic diseases, jaundice, malabsorption and maldigestion, food intolerance and food allergies, the impact of aging on the upper digestive tract (including the role of medications and drug interactions), and the brain gut connection. The appendices of the book offer coverage of related problems, including belching, nausea and vomiting, dry mouth and bitter taste, difficulty in tasting, lump in the throat, butterflies, difficulties in swallowing, delayed stomach emptying, the effects of diabetes on the upper digestive system, and the controversy over yeast. The author hopes to foster a cooperative dialogue between patients and their physicians as they work together to diagnose and manage upper digestive tract problems. A subject index concludes the book. 8 figures. 6 tables.

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Good Food for Bad Stomachs Source: New York, NY: Oxford University Press. 1997. 240 p. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $12.95 plus shipping and handling. ISBN: 0195126556. Summary: This book presents a detailed look at present knowledge about the role of eating habits in preventing, causing, and treating the many disorders that plague the gastrointestinal tract and its associated digestive glands, the liver, the gallbladder, and the pancreas. The author begins with three chapters that discuss nutrition and digestion, focusing on the elements of a realistic, reasonable diet. Other portions of the book are devoted to intestinal gas, constipation, diarrhea, the effect of aging, the effects of food on drug absorption, and the many effects of drugs on food absorption. The bulk of the chapters treat the kinds of disorders that can and do occur from one end of the digestive tract to the other, and the role of diet in these disorders. The author covers esophagitis, swallowing disorders, inflammation and ulcers of the stomach and duodenum (including peptic ulcer and gastritis), gallstones, pancreatitis, acute and chronic liver disease, traveler's diarrhea, constipation, inflammation and defects of the small intestine, celiac disease (gluten enteropathy), kidney oxalate stones, and the role of diet in colonic polyps and colon and rectal cancer. The author also discusses food intolerances, allergies, and reactions. The book concludes with a subject index. 14 tables.

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Gastroesophageal Reflux Disease: A Clinician's Guide Source: West Islip, NY: Professional Communications, Inc. 1997. 125 p. Contact: Available from Professional Communications Inc. 400 Center Bay Drive, West Islip, NY 11795. (800) 337-9838 or (516) 661-2852. Fax (516) 661-2167. PRICE: $17.95. ISBN: 1884735053. Summary: This handbook provides clinicians with an overview of gastroesophageal reflux, the return movement of gastric (stomach) contents into the lower esophagus. Gastroesophageal reflux disease (GERD) is characterized by a broad spectrum of clinical presentations, from simple heartburn to ulcerative esophagitis, esophageal stricture, and Barrett's metaplasia with its tendency to become malignant. The author notes that the progression from transient reflux to heartburn to esophageal injury is dependent on a number of anatomic and physiologic factors associated with the structural and functional integrity of the lower esophageal sphincter or LES (the muscle between the esophagus and the stomach). The handbook focuses on this progression, and well as on the pathogenesis and management of GERD. An introduction and seven chapters cover the natural history, pathophysiology, symptoms, diagnosis, complications, nonpharmacologic management, pharmacologic management, and surgical management of GERD. Information is provided in bulleted lists, with extensive figures and tables, for ease of access. Each chapter concludes with references; a subject index concludes the handbook. 20 figures. 10 tables. 139 references. (AA-M).

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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. •

Office Management of Digestive Diseases Source: Malvern, PA: Lea and Febiger. 1992. 246 p. Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This medical textbook presents information for primary care physicians dealing with the office management of common gastrointestinal diseases. Twenty-one chapters, each written by experts in the field, cover reflux esophagitis, dysphagia, peptic ulcer disease, chronic abdominal pain, diarrhea, diverticular disease, inflammatory bowel disease, colonic neoplasms, flexible sigmoidoscopy, chronic pancreatitis, irritable bowel syndrome, gallstones, hepatitis, cirrhosis, perianal diseases, premalignant gastrointestinal lesions, liver chemistry abnormalities, and flexible endoscopy. Each chapter includes numerous references and a subject index concludes the volume.

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Acid Related Disorders: Mystery to Mechanism, Mechanism to Management Source: Palm Beach, FL: Sushu Communications, Inc. 1995. 136 p. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. PRICE: $22.50. ISBN: 0963994301. Summary: Understanding of the mechanism of gastric acid secretion has progressed rapidly over the last decade. Following a brief historical perspective, the authors present a current view of the mechanism of acid secretion and the factors that regulate this process. Emphasis is on the most recent developments and those aspects relating directly to therapeutic control of acid secretion. Next, in light of these current concepts, the mechanism of action of antisecretory agents is presented. The authors note that the discovery of proton pump inhibitors has provided a more effective means of controlling acid secretion, with rapid healing of all upper gastrointestinal ulceration, including

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erosive esophagitis. The authors then describe the clinical use of these agents for symptom relief and management of acid-related disorders. The final section deals with possible future trends in the therapy of acid-related diseases, emphasizing the emerging role of Helicobacter pylori. The finding that infection with H. pylori contributes, along with acid, to the development of duodenal and non-NSAID gastric ulcers will further revolutionize the handling of these diseases. Each chapter offers selected references and a subject index concludes the book.

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

Reflux esophagitis and the Angelchik prosthesis; ISBN: 0444011722; http://www.amazon.com/exec/obidos/ASIN/0444011722/icongroupinterna

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

Esophagitis and Barrett's Esophagus in Children Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume Two. Philadelphia, PA: Current Medicine. 1999. p. 1258-1262. 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). Summary: Gastroesophageal (GE) reflux is responsible for most cases of esophagitis in children. This chapter on esophagitis and Barrett's esophagus in children is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. This chapter focuses on the special features of reflux esophagitis as it pertains to children. The specific mechanisms that lead to reflux esophagitis in children are similar to those in adults, i.e., transient lower esophageal sphincter relaxations, hypotonic lower esophageal sphincter,

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poor esophageal clearance, hiatal hernia, and delayed gastric emptying. Certain underlying disorders predispose children to pathologic GE reflux: neurologic impairment, repaired esophageal atresia, chronic lung disease (especially cystic fibrosis), and hiatal hernia. As in adults, upper GI endoscopy usually is the definitive study to determine the presence of esophagitis or Barrett's esophagus. In nonerosive reflux esophagitis, symptoms usually respond to measures such as lifestyle changes and prokinetic drugs or H2 receptor antagonists. Erosive esophagitis usually is chronic and relapsing, with the risk of stricture formation, and usually requires antireflux surgery or long term proton pump inhibitor use. Barrett's esophagus (BE), the presence of precancerous cells in the esophagus, is much less prevalent in children than in adults, and in childhood BE there is a high prevalence of serious, underlying coexisting disorders. Comorbidities can include neurologic impairment, chronic lung disease, esophageal atresia, and problems arising from chemotherapy for malignancies. 1 table. 27 references. •

Pill-Induced Esophagitis Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 91-96. 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). Summary: Numerous medications injure the esophagus by a variety of means. This chapter on pill induced esophagitis is from a textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. Some drugs, including immunosuppressive agents, xanthines, and calcium channel blockers, injure the esophagus because of their systemic side effects; nonsteroidal antiinflammatory drugs predispose to reflux damage through incompletely explained mechanisms; and bulk laxatives and sucralfate occasionally form obstructing esophageal bezoars (a concretion of hair or vegetable fibers). Other potentially caustic medications taken in pill form may fail to transit the esophagus, dissolve, and cause local esophageal injury. This chapter focuses on this last type of injury. Most pill induced esophageal injuries occur in patients with normal esophageal structure and function. The presentation is dominated by pain and may be so severe as to prevent adequate oral hydration. No diagnostic procedure is usually necessary; endoscopy is indicated when symptoms are gradual in onset, atypical, or persistent. The first step in treatment is to stop taking the offending pill, if possible, thus preventing exacerbation of the injury. Pain subsides within days to weeks in most uncomplicated cases of pill induced esophageal injury. Esophageal perforation and hemorrhage are rare but life threatening complications that require immediate specific, aggressive treatment. The author reviews injuries caused by specific pills, including antimicrobial and antiviral pills, antiinflammatory pills, potassium chloride, quinidine, alprenolol, and ferrous sulfate or succinate, alendronate and pamidronate pills, and sustained release pills. A few simple steps can reduce the incidence of pill induced esophagitis: all oral medications taken in pill form should be taken with at least 120 mL of fluid and patients should remain upright for at least 10 minutes after swallowing pills. 5 figures. 4 tables. 23 references.

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Esophagitis Source: in Feigin, R.D. and Cherry, J.D., eds. Textbook of Pediatric Infectious Diseases. 4th ed. Volume 1. Philadelphia, PA: W.B. Saunders Company. 1998. p. 562-566. 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. PRICE: $315.00. ISBN: 0721664482. Summary: This chapter on esophagitis is from a textbook on pediatric infectious diseases. The authors stress that infectious esophagitis is distinct from other gastrointestinal (GI) infections because it is rare in previously healthy persons, is predominantly caused by fungal and viral agents, and is usually a sign of immunodeficiency (which can be due to acquired, drug-induced, or congenital causes). Infection by multiple organisms is common in these patients. Even in normal children, infectious esophagitis is commonly associated with conditions that compromise esophageal defense mechanisms. The authors consider the pathophysiology and causative organisms, the typical clinical presentation, the differential diagnosis (including the use of esophagoscopy, biopsies, and brushings), treatment options, and prognosis. Treatment options are summarized for esophagitis caused by Candida fungus, viruses, and bacteria. Patients with AIDS respond more poorly to the drug therapy than immunocompetent patients. Surgery is required for fistulas, obstruction, and perforations that may occur (most common with Candida esophagitis). 5 figures. 2 tables. 39 references. (AA-M).

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Acid in the Gullet: Heartburn, Esophagitis, and Hiatal Hernia Source: in Janowitz, H.D. Indigestion: Living Better with Upper Intestinal Problems from Heartburn to Ulcers and Gallstones. New York, NY: Oxford University Press. 1992. p. 41-57. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $11.95 plus shipping and handling. ISBN: 019508554X. Summary: This chapter on acid related problems (heartburn, esophagitis, and hiatal hernia) is from a book that offers advice on how to take care of and avoid the whole complex of disturbances categorized as indigestion. The author reviews each of these three problems, covering their causes, symptoms, and the physiology of what is happening. Heartburn arises in the esophagus and results from the presence of the stomach's acid contents in the lower end of the esophagus. The acid has a direct irritating result because tissues there are not normally exposed to or prepared for the acid (compared to the stomach, which has a protective mucosal lining). The most important anatomical device protecting against heartburn is the lower esophageal sphincter (LES, which guards the opening between the esophagus and the stomach). The author explores the problem that can arise with a hiatal hernia, which can impair the LES's ability to prevent reflux of the stomach's contents into the esophagus. The LES pressure is also affected after a meal of fatty foods, by smoking, and by the presence of acid in the stomach (including the role of stomach emptying). The author also discusses diagnostic testing for acid reflux; treatment options, including habits and dietary modifications, and drug therapy; and general measures for relieving heartburn, including the role of exercise. Following is a discussion of the condition of active inflammation of the esophagus (esophagitis), including its diagnosis, medical treatment, surgery, and the problem of Barrett's esophagus. The chapter concludes with a

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discussion of the treatment options for hiatal hernia, focusing on the decision about surgical treatment for the condition. •

Sore Mouth or Difficulty Swallowing (Stomatitis, Esophagitis, Mucositis) Source: in Dodd, M.J. Managing the Side Effects of Chemotherapy and Radiation Therapy: A Guide for Patients and Their Families. 3rd ed. San Francisco, CA: School of Nursing, University of California, San Francisco. 1996. p. 110-112. Contact: Available from UCSF Nursing Press. School of Nursing, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0608. (415) 476-2626. PRICE: $26.00 per copy. ISBN: 0943671120. Summary: This chapter on mouth problems resulting from chemotherapy is from a handbook designed to help patients and their families get through cancer treatment and on the road to recovery. This chapter discusses sore mouth and difficulty in swallowing (stomatitis, esophagitis, mucositis). The author lists associated drugs that may contribute, describes what can happen, notes the anticipated duration of the complication, and then lists recommended self-care measures. Self-care measures focus on oral hygiene and proper nutrition.

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Diagnosis and Treatment of Reflux Esophagitis Source: in Danzi, J.T.; Scopelliti, J.A., eds. Office Management of Digestive Diseases. Malvern, PA: Lea and Febiger. 1992. p. 1-10. Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This chapter, from a medical textbook about the office management of common gastrointestinal diseases, discusses the diagnosis and treatment of reflux esophagitis. Topics include the clinical manifestations of the condition, its pathophysiology, medical treatment, diagnostic testing, complications, and surgical therapy. Diagnostic tests covered include barium esophagography, upper gastrointestinal endoscopy, the Bernstein test, ambulatory pH monitoring, and esophageal manometry. 1 table. 35 references.

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Other Causes of Esophagitis Source: in Katzka, D.A. and Metz, D.C., eds. Esophagus and Stomach. Orlando, FL: Mosby, Inc. 2003. p. 17-38. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $89.95. ISBN: 323018866. Summary: When most physicians consider esophagitis, they think of reflux-induced injury. This chapter explores the causes of non-reflux esophagitis and discusses clinical manifestations, diagnosis, and treatment. The chapter is from a textbook on the esophagus and stomach in which the authors focus on differential diagnosis, pitfalls, and evidence-based management approaches. The chapter covers infectious esophagitis (including candida esophagitis, herpes simplex virus esophagitis, cytomegalovirus esophagitis, and esophagitis in the AIDS patient), pill-induced esophagitis, corrosive esophagitis, and radiation esophagitis. For each condition, the authors explore background, epidemiology, pathogenesis, diagnosis, therapy, and complications. The

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chapter begins with a chapter outline, includes extensive tables and illustrations, and concludes with a list of recommended readings. 8 figures. 2 tables. 14 references.

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CHAPTER 6. MULTIMEDIA ON ESOPHAGITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on esophagitis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on esophagitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “esophagitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “esophagitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on esophagitis: •

What You Really Need to Know About Esophagitis and Hiatus Hernia Source: [Toronto, Ontario, Canada]: Videos for Patients. 1994. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $99.00 (Canadian); contact producer for current price in American dollars. Order Number VFP021. Summary: This patient education videotape provides information about esophagitis and hiatus hernia. The videotape begins with a brief sketch featuring comedian John Cleese and narrator Dr. Robert Buckman illustrating the difficulties sometimes experienced by patients during the traditional doctor's explanation. Topics include a definition of esophagitis, how esophagitis is caused, the contribution of hiatus hernia to esophagitis, the symptoms of esophagitis, diagnostic considerations, drug therapy for esophagitis, and dietary and lifestyle modifications that can reduce problems with

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esophagitis. Dr. Buckman presents the medical facts, using models, simple diagrams, and graphics to supplement his explanation, and avoiding medical jargon as much as possible.

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

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

Pantoprazole superior to ranitidine in preventing reflux esophagitis relapse Source: Reuters Medical News Date: August 17, 2001

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Inhaled allergens cause eosinophilic esophagitis in mice Source: Reuters Medical News Date: December 27, 2000

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Reflux Esophagitis In Infants May Actually Be Food Intolerance Source: Reuters Medical News Date: March 19, 1996

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Omeprazole Effective In Children With Esophagitis Refractory To Treatment With Ranitidine Source: Reuters Medical News Date: March 30, 1995 The NIH

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

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

Common Gastrointestinal Disorders in Infants Source: Messenger. 8(3): 1-3. 1997. Contact: Available from American Pseudo-obstruction and Hirschsprung's Disease Society (APHS). 158 Pleasant Street, North Andover, MA 01845. (508) 685-4477. Fax (508) 685-4488. E-mail: [email protected]. Summary: Gastrointestinal (GI) disorders are common in pediatric patients, thus most primary care physician assistants will address several types of GI disorders each day. That is why it is essential that practicing physician assistants be familiar with therapy for the most common pediatric GI disorders. This newsletter article briefly reviews the definition, epidemiology, and treatment of colic, gastroesophageal reflux (GER), and pyloric stenosis, but the primary focus is appropriate therapeutic management of these disorders. Colic broadly refers to unexplained and excessive crying in a healthy infant; the behavior primarily occurs in the evening hours between 5 pm and midnight. Treatment of a child with colic initially includes performing a complete history and physical examination, as well as plotting the child's growth curves. Parent reassurance and strategies to help the baby with gas cramps also prove useful. GER is associated with an incompetent lower esophageal sphincter, coupled with increased intraabdominal pressure from crying and straining. Flexible endoscopy and esophageal biopsy can evaluate the severity of esophagitis. Treatment depends on severity and can range from behavioral changes (more frequent, smaller meals) to surgery. Pyloric stenosis is a condition in which the stomach is partially blocked from emptying into the small intestine due to the hypertrophied pyloric muscle. Surgical pyloromyotomy is a relatively minor operation in which the hypertrophied pylorus and antral muscular layers are incised, leaving the mucosa intact. 11 references.

•

Is Cyclic Vomiting Different from Chronic Vomiting? Source: Code V. p. 5. Spring 1994. Contact: Available from Cyclic Vomiting Syndrome Association. 13180 Caroline Court, Elm Grove, WI 53122. (414) 784-6842. Fax (414) 821-5494. E-mail: [email protected]. PRICE: Single copy free.

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Summary: In this brief letter, a physician reviews the differences between cyclic vomiting and chronic vomiting. The author reports on his observations that, of children who were vomiting repeatedly for more than three months duration, one-third had the cyclic pattern and two-thirds had the chronic pattern. He goes on to describe the differences, including the criteria used to separate the cyclic from chronic groups; addresses the problem of dehydration; and notes the different etiologies of the two types of vomiting. Children with cyclic vomiting were more likely to have disorders outside the gastrointestinal tract, such as abdominal migraine, sinus infection, or metabolic disorders. Children with chronic vomiting were more likely to have diseases within the gastrointestinal tract, including esophagitis, gastritis (Helicobacter infection), duodenitis (acid-induced), Giardia, and irritable bowel syndrome (IBS). •

Malnutrition in the Hemodialysis Patient Source: Renal Nutrition Forum. 14(4): 1-4. Fall 1995. Contact: Available from Renal Nutrition Forum. 2246 Poinciana Road, Winter Park, FL 32792. (407) 774-0631. Summary: This article presents a brief overview of research addressing nutritional status in the hemodialysis (HD) patient and the relationship between malnutrition, morbidity, and mortality. The article is also intended to help the dietitian in preventing malnutrition in the HD patient by offering suggestions for therapy. Dialysis factors which may contribute to malnutrition include an increase in muscle protein degradation caused by blood contact with the dialyzer membrane; inadequate dialysis resulting in a uremic state which leads to nausea, vomiting, and loss of appetite; and loss of amino acids and peptides in dialysate. Hormonal disturbances include insulin resistance, increased circulating levels of catabolic hormones such as insulin and parathyroid hormone, and decreased levels of anabolic hormones such as growth factor and erythropoietin caused by deterioration of kidney function. Gastrointestinal factors include gastroparesis, malabsorption, gastritis, esophagitis, and constipation. The author reports on studies documenting that malnutrition greatly increases morbidity and mortality in the HD patient. HD patients should ingest 1.2 grams of protein per kilogram of actual body weight, where 50 percent is high biological value protein. An adequate energy intake is vital for the efficient utilization of dietary protein. The most important factor in improving malnutrition in this population is to assure adequate dialysis. The author concludes with a section on interventions for patients who continue to have poor appetites, even if dialysis delivery is optimal. 1 table. 15 references.

•

Antacids Source: Digestive Health Matters. 3(4): 1-3. Winter 2001. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. Website: www.iffgd.org. Summary: This article, from a health newsletter produced by the International Foundation for Functional Gastrointestinal Disorders (IFFGD), reviews the use of antacids. The author first notes the strength of gastric (stomach) acid and the wealth of new drugs available to treat problems with gastroesophageal reflux (return of gastric acid to the esophagus). The author then describes antacids, including the history of their use, how they work, and their components: sodium bicarbonate, magnesium hydroxide, aluminum hydroxide, and calcium carbonate. Additional components may include peppermint flavoring, antiflatulents (simethicone), and alginic acid. Most commercial

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antacids contain two or more components. Readers are urged to learn about these components and read the labels of the commercially available antacids, in order to make informed choices. The author notes that antacids are obsolete for the primary treatment of peptic ulcer. However, they seem to help many of those with bloating or nonulcer dyspepsia. Antacids by themselves, or combined with alginate, are very helpful for the relief of heartburn, but are ineffective for esophagitis and other complications of gastroesophageal reflux disease (GERD). If antacids are needed regularly for more than two weeks, the author recommends that a physician be consulted for diagnosis and appropriate treatment. 1 table. 2 references. •

Heartburn: Don't Ignore the Fire Source: Mayo Clinic Health Letter. 18(8): 1-3. August 2000. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This health newsletter article reviews heartburn, the burning sensation behind the breastbone, often accompanied by a sour taste in the back of the mouth. Heartburn is the result of stomach acid flowing up into the esophagus (gastroesophageal reflux). The article reviews the anatomy of the stomach and esophagus, and notes the factors that can result in heartburn, including simply overeating, or a weakened or abnormally relaxed esophageal sphincter. Frequent heartburn is called gastroesophageal reflux disease (GERD); people with GERD may also experience nausea, sore throat, hoarseness, wheezing, and a cough. Untreated, GERD can lead to inflammation of the esophagus (esophagitis) or to a precancerous condition called Barrett's esophagus. The article focuses on practical strategies to help prevent heartburn: control weight, avoid foods or beverages that can trigger heartburn, wear loose clothing, avoid lying down for 2 hours after eating, do not smoke, chew gum after meals, and drink adequate water when taking medications. Along with these lifestyle changes, nonprescription drugs that reduce painful stomach acid may relieve mild and occasional heartburn. These drugs include antacids and H2 blockers such as famotidine (Pepcid), nizatidine (Axid), ranitidine (Zantac), and cimetidine (Tagamet). When heartburn becomes frequent, readers are counseled to seek medical assistance. Diagnosis may include endoscopy and a pH monitoring test. After diagnosis, prescription medications may include stronger H2 blockers and proton pump inhibitors such as lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex). Surgery may be indicated when drug therapy and lifestyle changes are not effective. One sidebar reports on new endoscopic treatments for heartburn; another sidebar cautions readers about the side effects of chronic heartburn. 1 figure.

•

Reflux and Early Laryngeal Carcinoma Source: Visible Voice. 4(1): 1-5, 19-23. January 1995. Contact: Available from Center for Voice Disorders of Wake Forest University. Department of Otolaryngology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1034. (910) 716-4161. Summary: This newsletter article reports on a prospective study of 50 consecutive patients with early laryngeal carcinoma (cancer) that used 24-hour pH monitoring. Results showed that 66 percent of the patients had abnormal pH studies. In addition, of the 17 patients with normal pH studies, five had esophagitis on barium esophagography. The article also discusses the role of smoking and alcohol

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consumption in the development of reflux disease. Other topics include laryngopharyngeal reflux disease (LPR); why patients with LPR don't have heartburn; problems posed by relatively insensitive diagnostic methods; and reflux as a likely cause of largyneal carcinoma. The article concludes with the presentation of two related case studies. 2 figures. 27 references. (AA-M).

Academic Periodicals covering Esophagitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to esophagitis. In addition to these sources, you can search for articles covering esophagitis 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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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 Institute7: •

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/

7

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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

•

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

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.8 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:9 •

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

•

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

•

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

•

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

•

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

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

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

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

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

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

•

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

8

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). 9 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 Gateway10 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.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “esophagitis” (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 10267 56 262 224 124 10933

HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 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.14 Simply search by “esophagitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

10

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

11

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). 12 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 13 14

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 Biologists15 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.16 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.17 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/.

15 Adapted 16

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. 17 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 esophagitis 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 esophagitis. 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 esophagitis. 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 “esophagitis”:

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Esophageal Cancer http://www.nlm.nih.gov/medlineplus/esophagealcancer.html Esophagus Disorders http://www.nlm.nih.gov/medlineplus/esophagusdisorders.html Gastroesophageal Reflux/Hiatal Hernia http://www.nlm.nih.gov/medlineplus/gastroesophagealrefluxhiatalhernia.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 esophagitis. 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: •

Understanding Reflux Esophagitis Source: Indianapolis, IN: Eli Lilly and Company. 1992. 8 p. Contact: Available from Eli Lilly and Company. Lilly Corporate Center, Indianapolis, IN 46285. (800) 545-5979 or (317) 276-2000. Fax (317) 277-1827. PRICE: Single copy free. Summary: This patient education brochure provides information about reflux esophagitis or gastroesophageal reflux disease (GERD). Topics covered include the physiology and function of the esophagus; factors that influence muscle valve pressure; symptoms; complications of chronic reflux; diagnostic tests; and treatment options, including lifestyle adjustments, medication, and surgery. The booklet concludes by encouraging readers to maintain a positive mental attitude, work closely with a health care provider, and follow treatment advice. The back cover of the brochure summarizes the suggestions in a checklist format. 4 figures. 1 table. 8 references. 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 esophagitis. 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

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specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to esophagitis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with esophagitis. 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 esophagitis. 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 “esophagitis” (or a synonym), and you will receive information on all relevant organizations listed in the database.

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Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “esophagitis”. 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 “esophagitis” (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 “esophagitis” (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.18

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

18

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)19: •

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)

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

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

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

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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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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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/

19

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

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•

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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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

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

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

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

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

•

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

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

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

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

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

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

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

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

•

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

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

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

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

•

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

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

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

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•

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

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

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

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Esophagitis Esophagitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001153.htm Esophagitis Candida Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000643.htm Esophagitis CMV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000644.htm Esophagitis herpes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000646.htm

•

Signs & Symptoms for Esophagitis Difficulty swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm

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Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Joint pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Leukemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001299.htm Mouth sores Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003059.htm Pain when swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003116.htm Swallowing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Esophagitis Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm Cold agglutinins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003549.htm EGD (esophagogastroduodenoscopy) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003888.htm Endoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003338.htm Esophagogastroduodenoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003888.htm Throat swab culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003746.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm Upper GI and small bowel series Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003816.htm

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Urine culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003751.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Esophagitis Burn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000030.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Immune response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Oral hygiene Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001957.htm

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

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

•

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

•

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

•

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

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ESOPHAGITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acoustic: Having to do with sound or hearing. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acridine Orange: Cationic cytochemical stain specific for cell nuclei, especially DNA. It is used as a supravital stain and in fluorescence cytochemistry. It may cause mutations in microorganisms. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually

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referred to as adolescence lie between 13 and 18 years of age. [NIH] 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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU]

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Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] 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] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines

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include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] 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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU]

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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] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this 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] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [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

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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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aquaporins: Membrane proteins which facilitate the passage of water. They are members of the family of membrane channel proteins which includes the lens major intrinsic protein and bacterial glycerol transporters. [NIH] Aqueous: Having to do with water. [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] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]

Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU]

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Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophic Gastritis: Chronic irritation of the stomach lining. Causes the stomach lining and glands to wither away. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autosuggestion: Suggestion coming from the subject himself. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Balloon dilation: A treatment for benign prostatic hyperplasia or prostate enlargement. A tiny balloon is inflated inside the urethra to make it wider so urine can flow more freely from the bladder. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Belching: Noisy release of gas from the stomach through the mouth. Also called burping. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH]

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Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Bezoar: A ball of food, mucus, vegetable fiber, hair, or other material that cannot be digested in the stomach. Bezoars can cause blockage, ulcers, and bleeding. [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] Bile Reflux: Reflux of bile mainly into the upper digestive tract, but also into the pancreas. [NIH]

Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH]

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Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiole: The smaller airways of the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH]

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Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Butterflies: Slender-bodies diurnal insects having large, broad wings often strikingly colored and patterned. [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] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary

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for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell,

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enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH]

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Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] 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] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colonic Neoplasms: Tumors or cancer of the colon. [NIH] Colonic Polyps: Pedunculated or sessile growths arising from the mucous membrane of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH]

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Combined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, radioimmunotherapy, chemoradiotherapy, cryochemotherapy, and salvage therapy are seen most frequently, but their combinations with each other and surgery are also used. [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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

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biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which

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are followed over a period of time. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystamine: A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. [NIH] Cysteamine: A radiation-protective agent that oxidizes in air to form cystamine. It can be given intravenously or orally to treat radiation sickness. The bitartrate has been used for the oral treatment of nephropathic cystinosis. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH]

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Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deglutition: The process or the act of swallowing. [NIH] 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] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] 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] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [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] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself

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throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [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] 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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] 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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH]

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Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]

symptoms

resulting

from

an

absent

or

Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenitis: An irritation of the first part of the small intestine (duodenum). [NIH] Duodenogastric Reflux: Reflux of duodenal contents into the stomach. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

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Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] 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] 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] Endoscopic retrograde cholangiopancreatography: ERCP. A procedure to x-ray the pancreatic duct, hepatic duct, common bile duct, duodenal papilla, and gallbladder. In this procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endosonography: Ultrasonography of internal organs using an ultrasound transducer sometimes mounted on a fiberoptic endoscope. In endosonography the transducer converts electronic signals into acoustic pulses or continuous waves and acts also as a receiver to detect reflected pulses from within the organ. An audiovisual-electronic interface converts the detected or processed echo signals, which pass through the electronics of the instrument, into a form that the technologist can evaluate. The procedure should not be confused with endoscopy which employs a special instrument called an endoscope. The "endo-" of endosonography refers to the examination of tissue within hollow organs, with reference to the usual ultrasonography procedure which is performed externally or transcutaneously. [NIH]

Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Health: The science of controlling or modifying those conditions, influences,

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or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] 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] 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] Epiglottis: Thin leaf-shaped cartilage, covered with mucous membrane, at the root of the tongue, which folds back over the entrance to the larynx, covering it, during the act of swallowing. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the

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liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Atresia: Congenital failure of the full esophageal lumen to develop that commonly occurs with tracheoesophageal fistula. Symptoms include excessive salivation, gagging, cyanosis, and dyspnea. [NIH] Esophageal Manometry: A test to measure muscle tone inthe esophagus. [NIH] Esophageal Motility Disorders: Disorders affecting the motor function of the upper or lower esophageal sphincters, the esophageal body, or a combination of these parts. The failure of the sphincters to maintain a tonic pressure may result in the impeding of the passage of food, regurgitation of food, or reflux of gastric acid into the esophagus. [NIH] Esophageal Stricture: A narrowing of the esophagus often caused by acid flowing back from the stomach. This condition may require surgery. [NIH] Esophageal Ulcer: A sore in the esophagus. Caused by long-term inflammation or damage from the residue of pills. The ulcer may cause chest pain. [NIH] Esophagectomy: An operation to remove a portion of the esophagus. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagoscopy: Endoscopic examination, therapy, or surgery of the esophagus. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] 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] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood

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vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion. [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] 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] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fever of Unknown Origin: Fever in which the etiology cannot be ascertained. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed

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silver to form a permanent image. [EU] 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] Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent. [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] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] 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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU]

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Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Fundus: The superior portion of the body of the stomach above the level of the cardiac notch. [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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [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] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] 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] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Hemorrhage: Bleeding in the gastrointestinal tract. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH]

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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 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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH]

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Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [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] Haematemesis: The vomiting of blood. [EU] Harmaline: Alkaloid isolated from seeds of Peganum harmala L., Zygophyllaceae. A CNS stimulant acting as a monoamine oxidase inhibitor. [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 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] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation.

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[NIH]

Hepatic: Refers to the liver. [NIH] Hepatic Duct, Common: Predominantly extrahepatic bile duct which is formed by the junction of the right and left hepatic ducts, which are predominantly intrahepatic, and, in turn, joins the cystic duct to form the common bile duct. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] 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]

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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU]

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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] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [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] Hypoglycemia: Abnormally low blood sugar [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [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] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the

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result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] 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 situ: In the natural or normal place; confined to the site of origin without invasion of

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neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious 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]

Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [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] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [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

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glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with 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] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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]

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Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [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]

Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [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] Laryngeal: Having to do with the larynx. [NIH] Laryngeal Mucosa: The mucous lining of the larynx; mainly stratified squamous epithelium in the upper part and ciliated columnar in the lower part of the larynx. [NIH] Laryngitis: Inflammation of the larynx. This condition presents itself with dryness and soreness of the throat, difficulty in swallowing, cough, and hoarseness. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

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Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] 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] 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]

Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune

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system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnesium Hydroxide: Magnesium hydroxide (Mg(OH)2). An inorganic compound that occurs in nature as the mineral brucite. It acts as an antacid with cathartic effects. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Manometry: Tests that measure muscle pressure and movements in the GI tract. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Assistance: Financing of medical care provided to public assistance recipients. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH]

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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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] 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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] 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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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]

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Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [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] Motor Neurons: Neurons which activate muscle cells. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Lining: The lining of GI tract organs that makes mucus. [NIH] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic

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method that allows simultaneous study of two or more dependent variables. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] 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] 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,

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and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nizatidine: A histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion. The drug is used for the treatment of duodenal ulcers. [NIH] Nodose: Having nodes or projections. [EU] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Odynophagia: A painful condition of the esophagus. [NIH] Oesophagitis: Inflammation of the esophagus. [EU] Office Management: Planning, organizing, and administering activities in an office. [NIH]

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Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [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] Oropharynx: Oral part of the pharynx. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [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] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH]

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Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilla: A small nipple-shaped elevation. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [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] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH]

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Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patch Tests: Skin tests in which the sensitizer is applied to a patch of cotton cloth or gauze held in place for approximately 48-72 hours. It is used for the elicitation of a contact hypersensitivity reaction. [NIH] 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]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perianal: Located around the anus. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] 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

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system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [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 Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] 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] Physician Assistants: Persons academically trained, licensed, or credentialed to provide medical care under the supervision of a physician. The concept does not include nurses, but does include orthopedic assistants, surgeon's assistants, and assistants to other specialists. [NIH]

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

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU]

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Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Chloride: Potassium chloride. A white crystal or crystalline powder used as an electrolyte replenisher, in the treatment of hypokalemia, in buffer solutions, and in fertilizers and explosives. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, 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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for

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exploring or sounding body cavities. [NIH] Proctitis: Inflammation of the rectum. [EU] 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] Prokinetic Drugs: Medicines that cause muscles in the GI tract to move food. An example is cisapride (SIS-uh-pryd) (Propulsid). [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propulsive: Tending or having power to propel; driving onward or forward; impelling to action or motion. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [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]

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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] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [NIH]

Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Public Assistance: Financial assistance to impoverished persons for the essentials of living through federal, state or local government programs. [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 Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Pyloric Stenosis: Obstruction of the pyloric canal. [NIH] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an

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antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [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] 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] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [NIH]

Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH]

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Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU]

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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] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivary Proteins: Proteins found in saliva and the salivary glands. These proteins show some enzymatic activity, but their composition varies in different individuals. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a

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person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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 broad physiological actions and distribution of this biochemical mediator. [NIH]

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Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [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] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simethicone: A mixture of dimethyl polysiloxanes and silica gel used as an antiflatulent. Without the addition of silica gel (dimethicone), it is used as an ointment base ingredient and skin protectant. [NIH] Singultus: Hiccup. [EU] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU]

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Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial 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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [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] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat,

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scaly cells. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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.

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[NIH]

Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [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] Sulfhydryl Compounds: Compounds containing the -SH radical. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Systemic: Affecting the entire body. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Technetium: The first artificially produced element and a radioactive fission product of

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uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Cartilage: The largest cartilage of the larynx consisting of two laminae fusing anteriorly at an acute angle in the midline of the neck. The point of fusion forms a subcutaneous projection known as the Adam's apple. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of

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restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheoesophageal Fistula: Abnormal communication between the esophagus and the trachea, acquired or congenital, often associated with esophageal atresia. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor alpha: Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to epidermal growth factor and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [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] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is

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converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unresectable: Unable to be surgically removed. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [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] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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

Vagal: Pertaining to the vagus nerve. [EU]

Dictionary 203

Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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] Vocal cord: The vocal folds of the larynx. [NIH] Void: To urinate, empty the bladder. [NIH] Waist circumference: To define the level at which the waist circumference is measured, a

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bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xanthines: Purine bases found in body tissues and fluids and in some plants. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH]

205

INDEX A Abdomen, 145, 153, 165, 176, 177, 178, 187, 197, 198, 203 Abdominal, 11, 22, 80, 104, 107, 109, 120, 145, 161, 169, 177, 185, 187, 202 Abdominal Pain, 80, 104, 109, 145, 169, 177, 202 Ablate, 41, 145 Ablation, 145 Acceptor, 145, 184, 200 Accommodation, 61, 145 Acetylcholine, 31, 145, 156, 157, 182, 183 Acetylcholinesterase, 31, 145 Acidity, 29, 62, 145 Acoustic, 145, 164 Acquired Immunodeficiency Syndrome, 59, 60, 70, 145 Acridine Orange, 23, 145 Adaptability, 145, 155 Adenovirus, 18, 145 Adjuvant, 145, 147 Adolescence, 145, 186 Adrenal Cortex, 146, 159 Adrenergic, 14, 43, 146, 147, 165, 191 Adsorption, 102, 146 Adsorptive, 146 Adverse Effect, 7, 146, 196 Aerobic, 13, 146 Aerosol, 146, 199 Afferent, 14, 27, 28, 146 Affinity, 146, 179, 196 Age of Onset, 39, 146 Agglutinins, 142, 146 Agonist, 146, 154, 183 Airway, 10, 11, 14, 21, 31, 146, 153, 204 Albumin, 146, 188 Alendronate, 5, 6, 45, 68, 73, 111, 147 Algorithms, 109, 147, 152 Alkaline, 10, 31, 45, 46, 59, 147, 148, 151, 154, 200 Alkaloid, 147, 171, 183, 191 Alleles, 25, 147 Allergen, 147, 161, 195 Allium, 61, 147 Alpha Particles, 147, 192 Alpha-helix, 147, 177 Alprenolol, 5, 111, 147 Alternative medicine, 118, 147

Aluminum, 95, 120, 147, 199 Aluminum Hydroxide, 95, 120, 147 Alveolar Process, 147, 193 Alveolitis, 33, 147 Ambulatory Care, 147 Ameliorating, 32, 147 Amine, 147, 172 Amino Acid Sequence, 148, 149 Ammonia, 7, 147, 148, 202 Ampulla, 148, 164 Anabolic, 120, 148 Anaerobic, 13, 148 Anal, 148, 167, 181 Analog, 148, 168 Analogous, 148, 162, 201 Anastomosis, 12, 53, 148 Anatomical, 11, 40, 41, 112, 148, 151, 156, 164, 174 Androgens, 146, 148, 159 Anesthesia, 43, 146, 148 Angina, 28, 148 Anginal, 147, 148 Animal model, 11, 12, 16, 22, 26, 55, 148 Anionic, 30, 148 Anions, 101, 146, 148, 176, 199 Anode, 148 Anomalies, 21, 148 Anorectal, 109, 148 Anorexia, 149, 169, 202 Antiallergic, 149, 159 Antibacterial, 149, 197 Antibiotic, 149, 197 Antibodies, 13, 31, 146, 149, 174, 179, 188, 192 Antibody, 38, 146, 149, 158, 165, 172, 173, 174, 175, 176, 179, 181, 192, 195, 197, 204 Antifungal, 149, 168, 177 Antigen, 146, 149, 158, 161, 172, 173, 174, 175, 179, 195 Antigen-presenting cell, 149, 161 Antihypertensive, 147, 149 Anti-infective, 32, 149, 173 Anti-inflammatory, 149, 150, 159, 170, 185 Anti-Inflammatory Agents, 149, 150, 159 Antimicrobial, 50, 111, 149 Antineoplastic, 149, 155, 159, 184 Antioxidant, 149, 150 Antiviral, 5, 111, 149

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Anus, 148, 149, 150, 153, 157, 168, 176, 186, 193 Aorta, 59, 149, 203 Apnea, 35, 149 Aponeurosis, 149, 168 Apoptosis, 16, 26, 31, 36, 149 Appendicitis, 109, 150 Applicability, 19, 150 Aquaporins, 30, 150 Aqueous, 150, 160, 173, 178 Arachidonic Acid, 150, 190 Arginase, 26, 150 Arginine, 26, 150, 183, 202 Arterial, 22, 150, 170, 173, 190 Arteries, 149, 150, 153, 159, 180 Arterioles, 150, 153, 154 Artery, 28, 150, 153, 159, 191, 203 Ascorbic Acid, 72, 150, 173 Aspergillosis, 150, 177 Asphyxia, 21, 150 Aspiration, 10, 27, 150 Aspirin, 5, 150 Assay, 39, 150 Asymptomatic, 21, 150, 185 Atmospheric Pressure, 100, 150 Atresia, 111, 150 Atrial, 84, 150, 151 Atrial Fibrillation, 84, 151 Atrium, 150, 151, 203 Atrophic Gastritis, 46, 151 Attenuation, 28, 151 Atypical, 107, 111, 151 Autodigestion, 151, 185 Autologous, 58, 151 Autonomic, 14, 24, 47, 54, 91, 92, 145, 151, 183, 186 Autonomic Neuropathy, 54, 151 Autopsy, 65, 151 Autosuggestion, 151, 173 B Bacteria, 12, 112, 146, 149, 151, 152, 166, 167, 169, 175, 180, 195, 197, 201, 202 Bactericidal, 32, 151 Bacteriophage, 151, 201 Bacteriostatic, 147, 151 Balloon dilation, 17, 47, 151 Barium, 47, 113, 121, 151 Basal Ganglia, 151, 168 Basophil, 151, 172 Belching, 107, 151 Benign, 10, 48, 75, 109, 151, 152, 168, 182, 192

Benign prostatic hyperplasia, 151 Benign tumor, 109, 152 Beta blocker, 5, 152 Bezoar, 73, 152 Bile Acids, 3, 12, 98, 152, 169 Bile Acids and Salts, 152 Bile duct, 22, 152, 156, 164, 172, 174 Bile Pigments, 152, 177 Bile Reflux, 3, 26, 68, 152 Biliary, 53, 106, 152, 158, 185 Biliary Tract, 152, 185 Bilirubin, 4, 26, 146, 152, 173 Biochemical, 27, 31, 39, 147, 152, 195 Biological Transport, 152, 162 Biopsy, 6, 13, 21, 30, 34, 39, 42, 64, 119, 142, 152 Biopsy specimen, 39, 152 Biosynthesis, 38, 150, 152, 195 Biotechnology, 44, 118, 127, 152 Bladder, 151, 152, 158, 190, 202, 203 Blastomycosis, 152, 177 Bloating, 40, 107, 121, 153, 169, 175, 177, 183 Blood Coagulation, 153, 154 Blood Platelets, 153, 195 Blood pressure, 149, 153, 170, 173, 181, 196, 203 Blood vessel, 31, 152, 153, 154, 155, 156, 164, 167, 178, 180, 186, 196, 203 Body Fluids, 153, 162, 196 Bolus, 28, 29, 35, 41, 153 Bolus infusion, 153 Bone Marrow, 153, 160, 166, 170, 171, 174, 178, 196, 198 Bone Resorption, 6, 153 Bowel, 109, 142, 148, 153, 162, 175, 176, 177, 196, 198, 202 Bowel Movement, 153, 162, 198 Brachytherapy, 153, 176, 192, 204 Bradykinin, 153, 183, 188 Bronchi, 153, 165, 201 Bronchial, 10, 31, 153, 172 Bronchiole, 31, 153 Bronchitis, 31, 153 Bronchoalveolar Lavage, 34, 153 Bronchoconstriction, 14, 15, 153 Bronchodilator, 15, 153 Bronchus, 153, 154 Buccal, 99, 103, 154, 198 Butterflies, 107, 154

207

C Calcium, 15, 22, 99, 103, 111, 120, 154, 158, 166, 173, 184, 185, 200 Calcium Carbonate, 120, 154 Calcium channel blocker, 111, 154 Calcium Channel Blockers, 111, 154 Calcium Oxalate, 154, 184 Candidiasis, 60, 71, 154 Candidosis, 154 Capillary, 153, 154, 194, 203 Capillary Fragility, 154, 194 Capsules, 5, 154, 162, 164 Carbachol, 23, 154 Carbohydrate, 154, 159, 170 Carbon Dioxide, 154, 160, 167, 169, 194, 202 Carboplatin, 91, 155 Carboxy, 23, 155 Carcinogenesis, 16, 26, 155, 156 Carcinogenic, 16, 31, 155, 175, 190 Carcinoma, 26, 33, 35, 54, 91, 121, 155, 183, 197 Cardia, 27, 62, 155 Cardiac, 28, 39, 151, 155, 164, 165, 166, 169, 182, 191 Cardiovascular, 151, 155, 195 Cardiovascular System, 151, 155 Carrier Proteins, 155, 188 Case report, 45, 49, 57, 81, 92, 93, 155, 157, 167 Case series, 155, 157 Catheter, 21, 29, 35, 155, 164 Cathode, 148, 155, 163 Cations, 101, 155, 176 Causal, 26, 35, 42, 155, 194 Caustic, 5, 111, 155 Celiac Disease, 57, 108, 155 Cell Adhesion, 31, 155 Cell Cycle, 155, 160, 191 Cell Death, 31, 149, 155, 182 Cell Division, 151, 155, 156, 180, 188 Cell Lineage, 55, 155 Cell membrane, 20, 152, 154, 155, 187 Cell proliferation, 16, 20, 36, 156, 176 Cell Respiration, 156, 194 Cell Transplantation, 156 Cellulose, 156, 168, 180, 188 Central Nervous System, 11, 145, 156, 163, 168, 170, 195 Cerebrovascular, 154, 156 Character, 156, 161, 170 Chemoembolization, 22, 156

Chemokines, 56, 156 Chemoprevention, 16, 39, 156 Chemopreventive, 16, 37, 156 Chemotherapy, 13, 33, 50, 60, 101, 111, 113, 143, 156, 194 Chest Pain, 28, 63, 100, 106, 107, 156, 166 Chin, 93, 156, 180 Chlorophyll, 156, 168 Cholangitis, 53, 156 Cholecystectomy, 22, 156 Cholesterol, 152, 156 Choline, 31, 145, 156 Cholinergic, 14, 43, 154, 157, 183 Chromatin, 150, 157, 183 Chromosomal, 24, 157 Chromosome, 24, 32, 157, 178 Chronic renal, 57, 157, 202 Cirrhosis, 109, 157, 203 Clamp, 15, 31, 157 Clinical Medicine, 67, 157, 189 Clinical study, 13, 157, 159 Clinical trial, 9, 16, 22, 29, 33, 73, 127, 157, 159, 160, 162, 181, 191, 192 Cloning, 31, 39, 152, 157 Coenzyme, 150, 157 Colitis, 109, 157, 177 Collagen, 27, 102, 148, 157, 188, 190 Colloidal, 146, 157, 199 Colon, 12, 38, 101, 102, 108, 109, 157, 174, 175, 177, 196, 202 Colonic Neoplasms, 109, 157 Colonic Polyps, 108, 157 Colonoscopy, 42, 157 Combined Modality Therapy, 92, 158 Common Bile Duct, 22, 158, 160, 172 Comorbidity, 39, 158 Complement, 158, 170, 188, 195 Complementary and alternative medicine, 91, 95, 158 Complementary medicine, 91, 158 Compliance, 11, 14, 40, 43, 158 Computational Biology, 127, 158 Concomitant, 4, 61, 159 Concretion, 111, 159 Cone, 13, 159 Confounding, 43, 159 Conjunctiva, 159 Conjunctivitis, 159 Connective Tissue, 150, 153, 157, 159, 167, 168, 170, 180, 200 Constipation, 108, 109, 120, 159, 177 Constriction, 159, 204

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Contraindications, ii, 159 Controlled clinical trial, 22, 159 Controlled study, 57, 60, 159 Coronary, 28, 159, 180 Coronary Thrombosis, 159, 180 Corpus, 58, 81, 159 Cortical, 159, 166, 195 Corticosteroid, 47, 71, 83, 159 Cross-Sectional Studies, 39, 159 Curative, 13, 40, 160, 200 Cutaneous, 152, 154, 160 Cyanosis, 160, 166 Cyclic, 119, 120, 160, 171, 183 Cyclin, 36, 160 Cyclosporine, 68, 160 Cystamine, 160 Cysteamine, 101, 160 Cysteine, 101, 156, 160 Cystic Duct, 158, 160, 172 Cystine, 160 Cytokine, 33, 74, 160 Cytomegalovirus, 49, 52, 57, 60, 113, 160, 168 Cytomegalovirus Infections, 160, 168 Cytoplasm, 150, 156, 160, 165, 183 Cytosine, 160, 168 Cytotoxic, 160, 174, 192 D Data Collection, 42, 160 Decarboxylation, 160, 172 Decidua, 160, 201 Degenerative, 161, 172 Deglutition, 21, 161 Dehydration, 120, 161 Deletion, 26, 150, 161 Delivery of Health Care, 161, 171 Dementia, 145, 161 Dendrites, 161, 182 Dendritic, 32, 161 Dendritic cell, 32, 161 Density, 13, 58, 161, 184 Dentifrices, 147, 161 Deprivation, 21, 161 Dermal, 102, 161 Desensitization, 31, 161, 174 Desiccation, 38, 161 Deuterium, 161, 173 Diagnostic procedure, 97, 111, 118, 161 Dialysate, 120, 161 Dialyzer, 120, 161, 171 Diaphragm, 40, 161, 172 Diarrhea, 104, 108, 109, 161, 175, 177

Diarrhoea, 161, 169 Dietitian, 120, 161 Diffusion, 38, 152, 161 Digestion, 51, 107, 108, 152, 153, 162, 163, 169, 175, 176, 178, 186, 198 Digestive system, 107, 162, 169, 181 Digestive tract, 53, 102, 107, 108, 151, 152, 162, 196, 197 Dihydroxy, 162, 194 Dilation, 153, 162 Dimethyl, 162, 196 Direct, iii, 3, 11, 17, 23, 26, 31, 37, 99, 103, 112, 157, 162, 185, 192, 193, 199 Distal, 25, 35, 38, 41, 67, 85, 162, 169 Diurnal, 154, 162 Diverticula, 106, 162 Diverticulitis, 109, 162 Diverticulum, 162 Dorsal, 14, 43, 162, 189 Dorsum, 162, 168 Dosage Forms, 99, 103, 162 Dose-limiting, 33, 162 Double-blind, 44, 57, 60, 76, 162 Drug Design, 30, 162 Drug Interactions, 107, 162 Duct, 148, 158, 162, 164, 166, 194, 198 Dumping Syndrome, 63, 163 Duodenal Ulcer, 7, 61, 78, 102, 107, 109, 163, 183 Duodenitis, 120, 163 Duodenogastric Reflux, 4, 62, 81, 163 Duodenum, 4, 16, 20, 108, 109, 152, 163, 164, 169, 185, 186, 195, 198 Dyes, 23, 163, 183 Dyspepsia, 8, 106, 107, 109, 163, 175 Dysphagia, 10, 40, 57, 75, 83, 93, 106, 109, 163 Dysphonia, 34, 163 Dysplasia, 12, 19, 20, 25, 26, 33, 38, 83, 163 Dyspnea, 163, 166 E Edema, 31, 163, 202 Effector, 145, 158, 163 Efferent, 14, 163 Efficacy, 8, 22, 40, 51, 55, 56, 57, 76, 88, 92, 162, 163 Elastic, 163, 170 Elastin, 157, 163 Electrolysis, 148, 155, 163 Electrolyte, 159, 163, 180, 189, 196, 202 Electrons, 149, 155, 163, 176, 184, 192 Electrophysiological, 15, 28, 163

209

Emaciation, 145, 163 Embryo, 155, 163 Emesis, 14, 163 Enamel, 164, 177 Endocarditis, 154, 164 Endogenous, 26, 164, 201 Endoscope, 164 Endoscopic retrograde cholangiopancreatography, 22, 164 Endosonography, 58, 164 Endothelial cell, 31, 164 Endothelium, 164, 183 Endothelium-derived, 164, 183 End-stage renal, 157, 164 Energy Intake, 120, 164 Enteric-coated, 99, 103, 164 Enteropeptidase, 164, 202 Environmental Health, 126, 128, 164 Enzymatic, 148, 154, 158, 165, 172, 194 Enzyme Inhibitors, 165, 188 Eosinophil, 32, 165 Eosinophilic, 6, 32, 44, 56, 57, 58, 60, 66, 67, 69, 71, 74, 77, 78, 83, 88, 92, 93, 117, 165 Eosinophilic Gastroenteritis, 67, 165 Epidemic, 8, 19, 165 Epidemiological, 8, 165, 167 Epidermal, 54, 100, 101, 165, 177, 201 Epidermal Growth Factor, 54, 100, 101, 165, 201 Epidermis, 165, 177, 189 Epigastric, 165, 185 Epiglottis, 11, 165 Epinephrine, 146, 165, 182, 183 Epithelial, 8, 16, 21, 26, 30, 31, 32, 39, 86, 99, 101, 103, 145, 152, 160, 165, 170, 172 Epithelial Cells, 16, 31, 32, 165, 172 Epithelium, 10, 20, 23, 32, 33, 36, 38, 42, 46, 164, 165, 169, 201 Epitope, 39, 165 Erythrocytes, 153, 165, 195 Erythropoietin, 120, 165 Escalation, 14, 34, 166 Esophageal Atresia, 56, 66, 111, 166, 201 Esophageal Manometry, 5, 36, 113, 166 Esophageal Motility Disorders, 106, 166 Esophageal Stricture, 48, 70, 74, 108, 166 Esophageal Ulcer, 5, 166 Esophagectomy, 66, 166 Esophagoscopy, 112, 166 Etidronate, 84, 166 Eukaryotic Cells, 166, 175

Evacuation, 159, 166, 169, 177 Excipients, 99, 103, 166 Excitability, 166, 191 Excitatory, 14, 43, 166, 170 Exocrine, 166, 185 Exogenous, 146, 164, 166, 187 Expiration, 166, 194 External-beam radiation, 166, 176, 192, 204 Extracellular, 159, 166, 196, 200 Exudate, 67, 166 Eye Infections, 145, 167 F Family Planning, 127, 167 Famotidine, 58, 59, 79, 121, 167 Fat, 19, 150, 152, 153, 159, 167, 170, 178, 196 Fatal Outcome, 167, 192 Fecal Incontinence, 109, 167 Feces, 159, 167, 198 Fertilizers, 167, 189 Fetus, 166, 167, 202 Fever of Unknown Origin, 65, 167 Fibrinogen, 167, 188 Fibrosis, 30, 33, 48, 63, 111, 167 Fistula, 49, 167, 169 Fixation, 167, 195 Flatulence, 109, 168 Flatus, 167, 168, 169 Flucytosine, 60, 168 Fluorescence, 15, 145, 168 Fluoroscopy, 35, 40, 168 Fold, 20, 168 Follow-Up Studies, 39, 168 Free Radicals, 76, 101, 149, 168 Fungi, 149, 150, 167, 168, 180, 182, 200, 202, 204 Fungus, 112, 154, 168, 182 G Galanin, 23, 168 Gallbladder, 107, 108, 145, 152, 156, 160, 162, 164, 168, 169 Gamma Rays, 168, 192 Ganciclovir, 33, 168 Ganglia, 145, 168, 182, 187 Ganglion, 15, 168 Gas, 11, 108, 109, 119, 148, 151, 154, 161, 168, 169, 173, 175, 177, 183, 191, 194, 199 Gas exchange, 169, 194 Gastrectomy, 53, 59, 67, 169 Gastric Acid, 4, 6, 7, 8, 10, 15, 22, 26, 67, 86, 102, 107, 109, 120, 166, 169, 183, 184

210

Esophagitis

Gastric Emptying, 9, 111, 169 Gastric Fundus, 4, 43, 169 Gastric Juices, 169, 186 Gastric Mucosa, 101, 107, 169 Gastrin, 6, 22, 55, 169, 172 Gastritis, 7, 49, 81, 83, 106, 108, 120, 169, 199 Gastroduodenal, 26, 109, 169 Gastroenteritis, 109, 169 Gastroenterologist, 40, 169 Gastroesophageal Reflux Disease, 4, 5, 8, 9, 11, 22, 23, 26, 29, 32, 35, 37, 39, 41, 54, 55, 57, 64, 65, 71, 80, 82, 85, 94, 100, 105, 106, 107, 108, 109, 121, 132, 169 Gastrointestinal Hemorrhage, 73, 169 Gastrointestinal tract, 11, 18, 28, 38, 85, 99, 106, 108, 120, 168, 169, 195, 197 Gastroparesis, 43, 106, 120, 169 Gene, 20, 24, 26, 30, 32, 33, 38, 39, 74, 101, 145, 147, 152, 170, 201 Gene Expression, 26, 30, 33, 170 Gene Expression Profiling, 30, 170 Gene Therapy, 74, 101, 145, 170 Genetic Engineering, 152, 157, 170 Genetics, 21, 170 Genital, 151, 170 Genotype, 25, 170, 187 Gestation, 170, 186 Gland, 146, 170, 185, 188, 190, 195, 198, 200 Glucocorticoids, 146, 159, 170 Glucose, 150, 156, 170, 175, 176 Glutamate, 28, 170 Gluten, 108, 155, 170 Glycerol, 150, 170, 187 Glycine, 148, 152, 170, 182, 195 Glycoprotein, 165, 167, 170, 179, 181 Goblet Cells, 33, 170 Governing Board, 171, 189 Grade, 5, 8, 11, 33, 50, 69, 76, 82, 86, 171 Grading, 52, 171 Graft, 49, 171, 174 Graft-versus-host disease, 49, 171 Granule, 32, 171 Granulocyte, 77, 83, 171 Granuloma, 35, 171 Guanylate Cyclase, 171, 183 H Haematemesis, 163, 171 Harmaline, 92, 171 Health Care Costs, 22, 171 Health Expenditures, 171

Heartburn, 8, 21, 29, 42, 51, 64, 79, 94, 98, 100, 105, 106, 107, 108, 109, 112, 121, 122, 171, 172, 175 Heme, 152, 171 Hemodialysis, 120, 154, 161, 171 Hemoglobinopathies, 170, 171 Hemorrhage, 5, 42, 109, 111, 171 Hemostasis, 42, 171, 195 Hepatic, 43, 146, 158, 164, 172, 181 Hepatic Duct, Common, 164, 172 Hepatitis, 109, 172 Hepatocellular, 22, 172 Hepatocellular carcinoma, 22, 172 Hepatocytes, 172 Heredity, 170, 172 Hernia, 5, 6, 11, 65, 71, 98, 111, 112, 115, 172 Herpes, 49, 62, 65, 67, 88, 113, 141, 172 Herpes Zoster, 172 Heterogeneity, 24, 146, 172 Hiatal Hernia, 6, 8, 11, 28, 41, 46, 66, 98, 107, 111, 112, 132, 172 Histamine, 22, 26, 70, 167, 172, 173, 183, 193 Histamine Release, 22, 172 Histidine, 172 Histology, 6, 7, 25, 39, 86, 109, 172, 185 Hoarseness, 35, 121, 172, 177 Homologous, 147, 170, 172, 195, 199 Hormonal, 120, 159, 172 Hormone, 14, 63, 159, 165, 169, 172, 175, 195, 197, 200 Humoral, 13, 172 Humour, 172, 173 Hybrid, 38, 173 Hydration, 111, 173 Hydrogen, 11, 101, 145, 147, 154, 161, 173, 181, 182, 184, 191, 199 Hydrogen Peroxide, 173, 199 Hydrolysis, 145, 150, 173, 188, 202 Hydroxylysine, 157, 173 Hydroxyproline, 148, 157, 173 Hyperalgesia, 28, 173 Hyperbilirubinemia, 173, 177 Hypercalcemia, 166, 173 Hyperplasia, 58, 173 Hypersensitivity, 15, 28, 147, 161, 165, 173, 186, 195 Hypersensitivity, Immediate, 173 Hypertension, 154, 173, 202 Hypertrophy, 151, 173 Hypoglycemia, 93, 173

211

Hypotensive, 11, 41, 173 Hypothalamus, 173, 188, 197 I Iatrogenic, 5, 67, 173 Idiopathic, 44, 67, 69, 174 Ileum, 174, 204 Imidazole, 172, 174, 193 Immune function, 174 Immune response, 13, 143, 145, 149, 159, 174, 195, 198, 203 Immune system, 149, 174, 179, 187, 204 Immunization, 174, 195 Immunocompromised, 47, 174 Immunodeficiency, 53, 112, 145, 174 Immunoglobulin, 149, 174, 181 Immunohistochemistry, 31, 38, 174 Immunologic, 109, 174, 192 Immunosuppression, 174, 184 Immunosuppressive, 111, 174, 199 Immunosuppressive Agents, 111, 174 Immunotherapy, 161, 174 Impaction, 57, 109, 174 Impairment, 43, 111, 163, 167, 174, 176 Implant radiation, 174, 176, 192, 204 In situ, 31, 38, 174 In Situ Hybridization, 31, 38, 175 In vitro, 14, 15, 20, 31, 37, 170, 175, 199, 200 In vivo, 14, 15, 16, 18, 21, 37, 68, 101, 170, 175, 199 Incision, 175, 176 Incompetence, 169, 175 Indigestion, 107, 112, 175 Infancy, 175 Infantile, 25, 175 Infarction, 159, 175, 180 Infectious Diarrhea, 109, 175 Inflammatory bowel disease, 109, 175 Ingestion, 7, 72, 175, 188, 200 Inhalation, 34, 146, 175, 188 Initiation, 175, 201 Inoperable, 13, 175 Inorganic, 100, 175, 179, 181 Inpatients, 74, 175 Insight, 28, 32, 175 Insufflation, 40, 175 Insulin, 120, 175, 176 Insulin-dependent diabetes mellitus, 176 Intercellular Junctions, 20, 176 Interleukins, 174, 176 Internal radiation, 176, 192, 204 Interstitial, 153, 176, 204

Intestinal, 12, 30, 33, 38, 62, 103, 107, 108, 109, 112, 155, 164, 176, 179 Intestinal Mucosa, 155, 176 Intestinal Obstruction, 109, 176 Intoxication, 176, 204 Intracellular, 15, 154, 175, 176, 183, 189, 193 Intravenous, 81, 143, 176, 185 Intrinsic, 40, 146, 150, 176 Invasive, 9, 18, 22, 27, 29, 85, 176 Involuntary, 167, 176, 182, 193, 197 Ionization, 176 Ionizing, 101, 147, 176, 192 Ions, 20, 145, 163, 173, 176 Irradiation, 33, 101, 176, 204 Irritable Bowel Syndrome, 109, 120, 177 Itraconazole, 60, 177 J Jaundice, 107, 173, 177 K Kb, 126, 177 Keratin, 33, 177 Keratinocytes, 31, 177 Ketoconazole, 60, 70, 71, 177 Kidney stone, 177, 184 Kinetic, 176, 177, 187 L Laparoscopy, 8, 22, 177 Large Intestine, 162, 165, 176, 177, 193, 196 Laryngeal, 11, 35, 121, 177 Laryngeal Mucosa, 36, 177 Laryngitis, 8, 27, 35, 177 Larynx, 10, 99, 103, 165, 177, 200, 201, 203 Laser therapy, 10, 177 Latent, 177, 189 Laxative, 177, 180 Lens, 150, 178 Lesion, 19, 39, 152, 171, 178, 202 Lethal, 19, 151, 178 Leucocyte, 165, 178 Leukemia, 142, 170, 178 Leukocytes, 25, 32, 153, 156, 176, 178, 183 Life Expectancy, 35, 178 Ligaments, 159, 178 Ligands, 23, 31, 178 Ligation, 43, 178 Linkage, 8, 24, 178 Lipid, 156, 170, 176, 178 Liposome, 33, 74, 178 Localization, 21, 174, 178 Localized, 21, 39, 72, 167, 175, 178, 181, 188, 195, 202

212

Esophagitis

Longitudinal Studies, 159, 178 Loop, 18, 172, 178 Lower Esophageal Sphincter, 5, 9, 11, 16, 34, 40, 77, 108, 110, 112, 119, 166, 169, 178 Lymph, 164, 173, 178, 198 Lymphatic, 164, 175, 178, 180, 196, 197 Lymphatic system, 178, 196, 197 Lymphocyte, 145, 149, 174, 178, 179 Lymphocyte Count, 145, 179 Lymphoid, 149, 178, 179 Lymphoma, 106, 179 Lysine, 173, 179, 202 M Macrophage, 77, 83, 179 Macrophage Colony-Stimulating Factor, 77, 179 Magnesium Hydroxide, 120, 179 Maintenance therapy, 4, 52, 179 Malabsorption, 107, 109, 120, 155, 179, 196 Malignant, 16, 19, 108, 109, 145, 149, 179, 182, 192 Malignant tumor, 109, 179 Malnutrition, 120, 146, 179 Mandible, 147, 156, 179, 193 Manifest, 6, 106, 179 Mannans, 168, 179 Manometry, 40, 41, 54, 85, 106, 179 Mastication, 100, 179 Mediate, 36, 179, 193 Mediator, 179, 195 Medical Assistance, 121, 179 Medical Records, 179, 194 Medicament, 147, 179 MEDLINE, 127, 179 Meninges, 156, 180 Meningitis, 177, 180 Mental, iv, 9, 126, 128, 132, 156, 161, 175, 180, 191, 195, 202 Mesenchymal, 165, 179, 180 Metabolic disorder, 120, 180 Metaplasia, 7, 12, 20, 25, 33, 37, 38, 41, 43, 62, 108, 180 Methylcellulose, 102, 180 MI, 45, 77, 143, 180 Microbe, 180, 201 Microbiology, 59, 81, 151, 180 Microorganism, 6, 180, 203 Microtubules, 180, 184 Midaxillary line, 180, 204 Millimeter, 180, 204 Mineralization, 103, 180

Mineralocorticoids, 146, 159, 180 Mitosis, 150, 180 Mobility, 40, 98, 99, 180 Mobilization, 99, 103, 180 Modeling, 162, 180 Modification, 18, 148, 170, 181, 191 Molecular, 20, 26, 30, 32, 36, 38, 39, 43, 127, 129, 148, 152, 158, 162, 167, 181, 193, 199, 201 Molecule, 32, 102, 149, 157, 158, 160, 163, 164, 165, 171, 173, 181, 184, 192, 193, 203 Monitor, 17, 27, 39, 83, 181, 183 Monoamine, 171, 181 Monoamine Oxidase, 171, 181 Monoclonal, 38, 176, 181, 192, 204 Monocyte, 179, 181 Mononuclear, 171, 179, 181 Morphological, 163, 168, 181 Morphology, 21, 181 Motility, 9, 14, 21, 31, 35, 47, 58, 83, 109, 181, 195 Motion Sickness, 181, 182 Motor Neurons, 43, 181 Mucinous, 168, 181 Mucins, 38, 170, 181, 194 Mucolytic, 153, 181 Mucosal Lining, 112, 181 Mucositis, 113, 181, 200 Mucus, 101, 152, 181, 202 Multicenter study, 39, 76, 181 Multivariate Analysis, 61, 181 Musculature, 11, 182 Mycosis, 182 Mycotic, 60, 182 Mydriatic, 162, 182 Myocardium, 180, 182 N Nausea, 14, 104, 107, 109, 120, 121, 162, 169, 175, 182, 183, 202 Necrosis, 149, 175, 180, 182 Neoplasia, 13, 16, 182 Neoplasm, 182, 202 Neoplastic, 36, 179, 182, 194 Nerve, 24, 47, 146, 148, 156, 161, 163, 168, 169, 179, 181, 182, 198, 201, 203 Nervous System, 146, 156, 179, 182, 186, 192, 199 Neural, 10, 21, 22, 43, 146, 172, 181, 182 Neural Pathways, 22, 182 Neurologic, 21, 111, 182 Neuromuscular, 43, 145, 182, 202 Neuromuscular Junction, 43, 145, 182

213

Neuronal, 31, 182 Neurons, 14, 28, 43, 161, 166, 168, 181, 182, 183, 199 Neuropathy, 151, 182 Neurotransmitter, 145, 148, 153, 168, 170, 172, 182, 183, 197, 198, 199 Neutralization, 31, 182 Neutrons, 147, 176, 182, 192 Neutrophils, 171, 178, 183 Nicotine, 31, 183 Nitric Oxide, 26, 43, 68, 77, 82, 83, 183 Nizatidine, 82, 121, 183 Nodose, 14, 183 Non-small cell lung cancer, 13, 92, 183 Nonulcer Dyspepsia, 107, 121, 183 Norepinephrine, 146, 182, 183 Nuclear, 53, 61, 66, 151, 163, 166, 168, 182, 183, 202 Nuclei, 145, 147, 163, 170, 180, 182, 183, 191 Nucleic acid, 160, 175, 183 Nucleus, 14, 43, 150, 157, 160, 161, 166, 168, 181, 182, 183, 191 Nutritional Status, 120, 183 O Occult, 42, 183 Odynophagia, 47, 183 Oesophagitis, 3, 6, 7, 8, 91, 92, 93, 183 Office Management, 109, 113, 183 Ointments, 162, 184, 185 Omeprazole, 8, 51, 55, 66, 69, 70, 72, 76, 79, 82, 91, 95, 118, 121, 184, 191 Opacity, 161, 184 Opportunistic Infections, 145, 184 Oral Health, 184 Oral Hygiene, 113, 184 Organ Culture, 184, 200 Oropharynx, 101, 184 Osmosis, 184 Osmotic, 30, 146, 184 Osteoporosis, 6, 147, 184 Otolaryngology, 10, 42, 121, 184 Outpatient, 184 Overdose, 17, 184 Oxalate, 108, 184 Oxidation, 145, 149, 160, 184 Oxygen Consumption, 184, 194 P Paclitaxel, 91, 184 Palate, 185, 198 Palliative, 185, 200 Pamidronate, 5, 111, 185

Pancreas, 106, 108, 145, 152, 162, 169, 175, 185, 195, 197, 201 Pancreatic, 107, 164, 169, 185 Pancreatic Ducts, 164, 185 Pancreatic Juice, 169, 185 Pancreatitis, 108, 109, 185 Papilla, 164, 185 Paraffin, 30, 185 Paralysis, 17, 31, 185, 197 Parasite, 185 Parasitic, 109, 185 Parasitic Diseases, 109, 185 Parathyroid, 120, 185, 200 Parathyroid Glands, 185 Parathyroid hormone, 120, 185 Parenteral, 164, 185 Parietal, 22, 184, 185 Parietal Lobe, 185 Paroxysmal, 84, 186 Partial remission, 186, 193 Particle, 178, 186, 201 Patch, 31, 69, 83, 186 Patch Tests, 83, 186 Pathogenesis, 11, 20, 22, 33, 42, 48, 75, 77, 92, 93, 108, 113, 186 Pathologic, 13, 45, 111, 150, 152, 154, 159, 173, 186, 193 Pathologic Processes, 150, 186 Pathophysiology, 19, 23, 40, 41, 106, 108, 112, 113, 186 Patient Education, 115, 132, 136, 138, 143, 186 Patient Satisfaction, 17, 186 Pediatrics, 21, 27, 39, 57, 76, 83, 84, 186 Pepsin, 53, 82, 186, 195 Peptic, 4, 6, 8, 22, 24, 36, 78, 80, 106, 107, 108, 109, 121, 186, 199 Peptic Ulcer, 22, 24, 78, 80, 106, 107, 108, 109, 121, 186 Peptide, 148, 164, 177, 186, 188, 190 Perception, 14, 159, 186, 195 Perforation, 5, 111, 186 Perfusion, 21, 186 Perianal, 109, 186 Perinatal, 21, 186 Peripheral blood, 58, 186 Peripheral Nervous System, 182, 186, 197, 198 Peripheral stem cells, 171, 187 Peristalsis, 28, 32, 187 Peritoneal, 161, 187 Peritoneal Dialysis, 161, 187

214

Esophagitis

Petroleum, 185, 187 Phagocyte, 179, 187 Pharmaceutical Solutions, 162, 187 Pharmacodynamic, 167, 187 Pharmacokinetics, 162, 187 Pharmacologic, 41, 108, 148, 187, 201 Pharynx, 21, 99, 103, 106, 169, 184, 187, 203 Phenotype, 33, 38, 187 Phospholipids, 167, 187 Phosphorus, 154, 185, 187 Physical Examination, 119, 187 Physician Assistants, 119, 187 Physiologic, 28, 36, 40, 108, 146, 152, 188, 193 Physiology, 11, 22, 40, 41, 106, 107, 109, 112, 132, 163, 169, 188 Pigment, 152, 188 Pilot study, 24, 42, 188 Pituitary Gland, 159, 188 Plague, 108, 188 Plants, 147, 155, 156, 170, 181, 183, 188, 194, 201, 204 Plasma, 83, 102, 146, 149, 155, 167, 171, 180, 188 Plasma cells, 149, 188 Plasma protein, 102, 146, 188 Platelet Aggregation, 183, 188 Platelets, 183, 188 Platinum, 178, 188 Pleated, 177, 188 Pneumonia, 27, 159, 188 Pneumonitis, 10, 13, 188 Poisoning, 169, 176, 182, 188 Polyp, 58, 188 Polypeptide, 43, 148, 157, 165, 167, 188, 197 Polyposis, 109, 189 Population Control, 30, 189 Port, 31, 189 Port-a-cath, 189 Posterior, 148, 162, 180, 185, 189 Postmenopausal, 147, 184, 189 Postoperative, 40, 189 Potassium, 5, 111, 180, 189, 191 Potassium Chloride, 5, 111, 189 Potentiates, 16, 189 Practice Guidelines, 128, 189 Precancerous, 111, 121, 156, 189 Preclinical, 16, 189 Precursor, 12, 24, 25, 39, 150, 156, 163, 165, 183, 189, 202

Predisposition, 30, 189 Premalignant, 10, 20, 23, 109, 189 Preoperative, 50, 189 Prevalence, 8, 13, 24, 25, 30, 37, 39, 42, 63, 69, 78, 111, 189 Prickle, 177, 189 Probe, 15, 35, 58, 189 Proctitis, 102, 190 Progression, 12, 26, 30, 36, 38, 42, 75, 108, 148, 190 Progressive, 50, 157, 161, 166, 182, 190, 202 Projection, 14, 183, 190, 200 Prokinetic Drugs, 111, 190 Proline, 157, 173, 190 Promoter, 18, 32, 33, 190 Prophylaxis, 64, 190 Propulsive, 35, 190 Prospective Studies, 55, 190 Prospective study, 39, 70, 121, 190 Prostaglandins, 16, 26, 68, 150, 190 Prostaglandins A, 68, 190 Prostaglandins D, 190 Prostate, 151, 190 Prosthesis, 110, 190 Protective Agents, 102, 154, 190 Protein S, 152, 190 Protocol, 10, 27, 34, 43, 191 Proton Pump Inhibitors, 22, 26, 36, 39, 86, 109, 121, 191 Protons, 147, 173, 176, 191, 192 Proto-Oncogene Proteins, 184, 191 Proto-Oncogene Proteins c-mos, 184, 191 Protozoa, 180, 191, 202 Psychic, 180, 191, 195 Psychoactive, 191, 204 Psychotherapy, 191, 193 Public Assistance, 179, 191 Public Policy, 127, 191 Pulmonary, 8, 10, 15, 153, 165, 191, 194, 203 Pulmonary Ventilation, 191, 194 Pulse, 181, 191 Pupil, 162, 182, 191 Pyloric Stenosis, 119, 191 Pylorus, 119, 163, 191 Q Quality of Life, 15, 17, 19, 29, 34, 35, 191 Quinidine, 5, 111, 191 Quinine, 191 R Rabies, 31, 192

215

Radiation, 13, 29, 54, 56, 74, 75, 91, 92, 101, 113, 160, 166, 168, 174, 176, 192, 194, 204 Radiation therapy, 13, 101, 166, 176, 192, 194, 204 Radioactive, 173, 174, 176, 183, 192, 199, 202, 204 Radiofrequency ablation, 22, 192 Radioimmunotherapy, 158, 192 Radiolabeled, 176, 192, 204 Radiological, 18, 22, 192 Radiology, 10, 56, 75, 85, 192 Radionuclide Imaging, 85, 192 Radiosensitization, 33, 192 Radiotherapy, 54, 56, 75, 77, 83, 91, 153, 176, 192, 204 Randomized, 15, 22, 25, 29, 43, 44, 51, 55, 57, 60, 68, 76, 77, 79, 82, 84, 93, 163, 192, 193 Randomized clinical trial, 15, 29, 77, 193 Ranitidine, 76, 88, 93, 95, 117, 118, 121, 193 Reassurance, 119, 193 Receptor, 4, 15, 18, 26, 36, 45, 70, 111, 149, 159, 167, 179, 183, 193, 195, 201 Receptors, Serotonin, 193, 195 Recombinant, 77, 83, 193, 203 Recombination, 170, 193 Rectal, 108, 193 Rectum, 148, 149, 153, 157, 162, 168, 169, 175, 177, 190, 193 Recurrence, 39, 42, 70, 92, 156, 193 Refer, 1, 154, 158, 167, 168, 172, 178, 183, 192, 193, 201 Reflex, 14, 193 Refraction, 193, 197 Refractory, 4, 26, 45, 51, 59, 118, 193 Regeneration, 37, 193 Regimen, 29, 36, 163, 193 Regurgitation, 17, 42, 106, 166, 169, 171, 193 Relapse, 4, 21, 58, 64, 80, 117, 193 Remission, 4, 179, 193 Resection, 41, 193, 196 Resorption, 103, 193 Respiration, 13, 41, 149, 155, 181, 194 Respiratory System, 10, 194 Retinal, 159, 194 Retrograde, 10, 15, 35, 40, 194 Retrospective, 25, 39, 41, 194 Retrospective Studies, 41, 194 Retrospective study, 39, 194 Retroviral vector, 170, 194

Risk factor, 6, 19, 20, 24, 30, 33, 36, 39, 42, 49, 50, 74, 80, 105, 190, 194 Rod, 157, 194 Rutin, 92, 194 S Saline, 153, 194 Saliva, 35, 38, 194 Salivary, 38, 100, 160, 162, 194, 198 Salivary glands, 38, 101, 160, 162, 194 Salivary Proteins, 38, 194 Salivation, 166, 194 Salvage Therapy, 158, 194 Schizoid, 194, 204 Schizophrenia, 195, 204 Schizotypal Personality Disorder, 195, 204 Scleroderma, 80, 195 Scleroproteins, 177, 195 Screening, 19, 41, 157, 195 Secretin, 23, 195 Secretory, 23, 39, 109, 184, 195, 199 Seizures, 186, 195 Senile, 184, 195 Sensibility, 173, 195 Sensitization, 28, 195 Sensor, 21, 195 Sepsis, 65, 195 Sequencing, 31, 195 Serine, 191, 195, 201 Serotonin, 15, 181, 182, 193, 195, 202 Serum, 13, 27, 55, 146, 158, 180, 196 Sessile, 157, 196 Shock, 196, 201 Short Bowel Syndrome, 109, 196 Side effect, 50, 111, 121, 146, 162, 196, 201 Sigmoid, 196 Sigmoidoscopy, 109, 196 Signs and Symptoms, 193, 196, 202 Simethicone, 120, 196 Singultus, 65, 196 Skeletal, 148, 157, 191, 196, 197 Skull, 196, 200 Small cell lung cancer, 196 Small intestine, 4, 101, 102, 108, 109, 119, 160, 163, 164, 165, 172, 174, 176, 196, 202 Smooth muscle, 153, 154, 172, 173, 196, 197, 198 Social Environment, 191, 196 Sodium, 120, 180, 191, 192, 196 Sodium Bicarbonate, 120, 196 Soft tissue, 38, 153, 196 Solid tumor, 18, 196 Solvent, 170, 184, 187, 196

216

Esophagitis

Soma, 45, 74, 197 Somatic, 101, 145, 172, 180, 186, 197, 203 Somatostatin, 22, 197 Spasm, 28, 84, 197, 200 Spastic, 177, 197 Specialist, 133, 162, 197 Species, 13, 14, 156, 165, 169, 173, 180, 181, 185, 191, 192, 197, 198, 200, 201, 203, 204 Specificity, 39, 146, 197 Spectrum, 83, 108, 177, 197 Sperm, 148, 157, 197 Sphincter, 9, 16, 40, 73, 84, 98, 110, 121, 177, 197 Spinal cord, 156, 168, 180, 182, 186, 193, 197 Spinous, 165, 177, 197 Spleen, 160, 178, 197 Squamous, 20, 32, 33, 36, 98, 177, 183, 197 Squamous cell carcinoma, 183, 197 Squamous Epithelium, 32, 33, 36, 98, 177, 197 Standard therapy, 4, 198 Stasis, 14, 198 Steel, 157, 198 Stem cell transplantation, 58, 198 Stem Cells, 166, 187, 198 Stenosis, 66, 81, 119, 198 Sterile, 185, 198 Steroids, 15, 159, 198 Stimulant, 171, 172, 198 Stimulus, 193, 198, 200 Stomach, 3, 5, 6, 7, 12, 14, 16, 21, 25, 27, 33, 41, 43, 98, 99, 101, 103, 106, 107, 108, 109, 112, 113, 119, 120, 121, 145, 151, 152, 155, 162, 163, 165, 166, 169, 172, 178, 182, 186, 187, 191, 193, 195, 196, 197, 198 Stomatitis, 60, 102, 113, 198 Stool, 157, 174, 177, 198 Stress, 7, 8, 14, 19, 40, 93, 112, 154, 169, 177, 182, 189, 198 Stricture, 5, 8, 27, 51, 53, 67, 73, 86, 111, 198 Subacute, 175, 198 Subclinical, 175, 195, 198 Subcutaneous, 163, 185, 198, 200, 204 Submaxillary, 165, 198 Subspecies, 197, 198 Substance P, 195, 198 Sucralfate, 45, 59, 81, 82, 86, 102, 111, 199 Suction, 64, 199 Sulfhydryl Compounds, 101, 199

Superoxide, 33, 74, 82, 101, 199 Superoxide Dismutase, 33, 74, 199 Supine, 5, 199 Supplementation, 12, 199 Suppression, 8, 29, 35, 159, 199 Suppressive, 36, 72, 199 Survival Rate, 41, 199 Suspensions, 102, 199, 202 Symptomatic, 4, 5, 8, 24, 48, 75, 98, 185, 199 Synapse, 146, 182, 199, 201 Synaptic, 182, 183, 199 Synaptic Transmission, 183, 199 Systemic, 111, 149, 153, 154, 165, 175, 176, 192, 195, 196, 198, 199, 204 T Tacrolimus, 71, 199 Technetium, 53, 199 Temporal, 15, 200 Tendon, 168, 200 Tetany, 185, 200 Therapeutics, 6, 14, 44, 58, 72, 181, 200 Thermal, 28, 182, 200 Thoracic, 68, 161, 200, 204 Threshold, 27, 29, 166, 173, 200 Thrush, 154, 200 Thymidine, 33, 200 Thymidine Kinase, 33, 200 Thyroid, 11, 185, 200 Thyroid Cartilage, 11, 200 Thyroid Gland, 185, 200 Tissue Culture, 20, 200 Tomography, 6, 68, 200 Tone, 22, 43, 166, 184, 200 Tonic, 166, 200 Tonus, 200, 201 Topical, 83, 173, 185, 196, 201 Toxic, iv, 100, 101, 182, 183, 187, 201 Toxicity, 13, 17, 31, 102, 162, 183, 199, 201 Toxicology, 45, 128, 201 Toxin, 17, 26, 201 Trachea, 59, 153, 154, 177, 187, 200, 201 Tracheoesophageal Fistula, 166, 201 Traction, 157, 201 Transcription Factors, 37, 201 Transduction, 36, 201 Transfection, 152, 170, 201 Transforming Growth Factor alpha, 53, 201 Transgenes, 33, 201 Translation, 148, 201 Transmitter, 145, 179, 183, 201

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Transplantation, 59, 68, 157, 174, 201 Trauma, 109, 166, 182, 185, 201 Tropism, 18, 201 Trypsin, 3, 12, 164, 201 Tryptophan, 157, 195, 202 Tumour, 168, 202 Tunica, 181, 202 U Ulcer, 7, 22, 42, 55, 75, 78, 102, 106, 107, 163, 166, 183, 199, 202 Ulceration, 8, 99, 103, 109, 186, 202 Ulcerative colitis, 84, 102, 109, 175, 202 Ultrasonography, 61, 74, 164, 202 Unresectable, 14, 202 Uraemia, 185, 202 Uranium, 200, 202 Urea, 150, 202 Urease, 7, 202 Urethra, 151, 190, 202 Urinate, 202, 203 Urine, 143, 151, 152, 154, 165, 177, 184, 202 Uterus, 159, 160, 202, 203 V Vaccines, 147, 202, 203 Vagal, 14, 28, 43, 202 Vagina, 154, 203 Vaginitis, 154, 203 Vagus Nerve, 202, 203 Varices, 43, 203 Vascular, 85, 154, 164, 173, 175, 183, 200, 203 Vasculitis, 31, 185, 203 Vasoactive, 43, 203 Vasodilator, 153, 172, 203 Vector, 185, 201, 203

Vein, 176, 183, 203 Venous, 43, 190, 203 Venous Pressure, 43, 203 Ventricle, 173, 191, 203 Venules, 153, 154, 203 Veterinary Medicine, 127, 203 Villous, 155, 203 Viral, 47, 65, 86, 112, 192, 201, 203 Virulence, 201, 203 Virus, 31, 49, 53, 65, 113, 145, 151, 170, 194, 201, 203 Viscera, 197, 203 Visceral, 28, 151, 203 Vitro, 15, 203 Vivo, 18, 20, 203 Vocal cord, 35, 203 Void, 36, 203 W Waist circumference, 19, 203 Wheezing, 121, 204 White blood cell, 149, 151, 165, 171, 178, 179, 181, 188, 204 Windpipe, 154, 187, 200, 204 Withdrawal, 43, 204 X Xanthines, 111, 204 Xenograft, 148, 204 X-ray, 142, 143, 155, 164, 168, 176, 183, 192, 204 X-ray therapy, 176, 204 Y Yeasts, 154, 168, 187, 204 Z Zoonoses, 192, 204

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Esophagitis

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Esophagitis