Gastroesophageal Reflux Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

GASTROESOPHAGEAL REFLUX DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R ...

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GASTROESOPHAGEAL REFLUX DISEASE 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., 1960Gastroesophageal Reflux Disease: 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: 0-497-00446-1 1. Gastroesophageal Reflux Disease-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 gastroesophageal reflux disease. 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 GASTROESOPHAGEAL REFLUX DISEASE................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Gastroesophageal Reflux Disease ................................................ 23 E-Journals: PubMed Central ....................................................................................................... 44 The National Library of Medicine: PubMed ................................................................................ 44 CHAPTER 2. NUTRITION AND GASTROESOPHAGEAL REFLUX DISEASE ......................................... 91 Overview...................................................................................................................................... 91 Finding Nutrition Studies on Gastroesophageal Reflux Disease................................................. 91 Federal Resources on Nutrition ................................................................................................... 93 Additional Web Resources ........................................................................................................... 93 CHAPTER 3. ALTERNATIVE MEDICINE AND GASTROESOPHAGEAL REFLUX DISEASE .................. 97 Overview...................................................................................................................................... 97 National Center for Complementary and Alternative Medicine.................................................. 97 Additional Web Resources ......................................................................................................... 100 General References ..................................................................................................................... 109 CHAPTER 4. PATENTS ON GASTROESOPHAGEAL REFLUX DISEASE ............................................. 111 Overview.................................................................................................................................... 111 Patents on Gastroesophageal Reflux Disease ............................................................................. 111 Patent Applications on Gastroesophageal Reflux Disease ......................................................... 123 Keeping Current ........................................................................................................................ 139 CHAPTER 5. BOOKS ON GASTROESOPHAGEAL REFLUX DISEASE ................................................. 141 Overview.................................................................................................................................... 141 Book Summaries: Federal Agencies............................................................................................ 141 Book Summaries: Online Booksellers......................................................................................... 143 Chapters on Gastroesophageal Reflux Disease........................................................................... 144 CHAPTER 6. MULTIMEDIA ON GASTROESOPHAGEAL REFLUX DISEASE ...................................... 149 Overview.................................................................................................................................... 149 Video Recordings ....................................................................................................................... 149 CHAPTER 7. PERIODICALS AND NEWS ON GASTROESOPHAGEAL REFLUX DISEASE ................... 153 Overview.................................................................................................................................... 153 News Services and Press Releases.............................................................................................. 153 Newsletter Articles .................................................................................................................... 155 Academic Periodicals covering Gastroesophageal Reflux Disease ............................................. 156 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 157 Overview.................................................................................................................................... 157 U.S. Pharmacopeia..................................................................................................................... 157 Commercial Databases ............................................................................................................... 160 Researching Orphan Drugs ....................................................................................................... 160 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 165 Overview.................................................................................................................................... 165 NIH Guidelines.......................................................................................................................... 165 NIH Databases........................................................................................................................... 167 Other Commercial Databases..................................................................................................... 169 APPENDIX B. PATIENT RESOURCES ............................................................................................... 171 Overview.................................................................................................................................... 171 Patient Guideline Sources.......................................................................................................... 171 Finding Associations.................................................................................................................. 185 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 187 Overview.................................................................................................................................... 187

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Preparation................................................................................................................................. 187 Finding a Local Medical Library................................................................................................ 187 Medical Libraries in the U.S. and Canada ................................................................................. 187 ONLINE GLOSSARIES................................................................................................................ 193 Online Dictionary Directories ................................................................................................... 198 GASTROESOPHAGEAL REFLUX DISEASE DICTIONARY .............................................. 199 INDEX .............................................................................................................................................. 253

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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 gastroesophageal reflux disease 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 gastroesophageal reflux disease, 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 gastroesophageal reflux disease, 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 gastroesophageal reflux disease. 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 gastroesophageal reflux disease, 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 gastroesophageal reflux disease. 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 GASTROESOPHAGEAL REFLUX DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on gastroesophageal reflux disease.

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

Identifying Patients with Gastroesophageal Reflux Disease: Validation of a Practical Screening Tool Source: Digestive Diseases and Sciences. 47(8): 1863-1869. August 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].

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Summary: A reliable, accurate noninvasive method for identifying patients with gastroesophageal reflux disease (GERD) in the primary care setting is needed. A population based, case-finding instrument may assist managed care organizations in identifying candidates for disease management or quality improvement programs. This article reports on a study undertaken to develop and validate a GERD case-finding instrument. A 12 item GERD Screener was developed based on literature review and expert opinion, with questions about heartburn and regurgitation frequency and severity and medication use, as well as demographics and exclusion criteria. Using a telephone interview in a medical group, the authors identified and enrolled 100 subjects with a history of GERD like symptoms and 103 controls. Each subject completed the GERD Screener, a validated gastrointestinal symptom questionnaire, the Digestive Health Symptom Index (DHIS), and was evaluated independently by two gastroenterologists using a structured format. The data showed that the GERD Screener demonstrated construct, convergent, and predictive validity. The Screener is shorter than existing validated instruments, practical, and easily administered, which may reduce the response and administrative burden. The Screener may serve as a valuable case-finding instrument in primary-care and managed-care organizations wishing to implement programs to improve the quality and efficiency of care. 1 figure. 4 tables. 28 references. •

Long-Term Management of Gastroesophageal Reflux Disease and Its Complications Source: American Journal of Gastroenterology. 92(4, Supplement): 30S-35S. April 1997. Summary: Although gastroesophageal reflux disease (GERD) is believed to be primarily a motor disorder, current medical therapy is based on the inhibition of acid secretion, since it is the deleterious effects of the acid reflux that lead to the symptoms and complications of GERD. This article outlines the longterm management of GERD and its complications. The author stresses that goals of longterm management include the relief of symptoms, healing of esophagitis and prevention of its relapse, and prevention of complications with safe, cost effective therapy. Maintenance therapy depends on disease severity. Prokinetic drugs have a limited role except in symptomatic nonerosive GERD. Likewise, H2-receptor antagonists are useful in relapsing, nonerosive GERD or in cases of mild initial esophagitis. For severe reflux esophagitis, even high doses of H2-receptor antagonists do not appear to be as effective as proton pump inhibitors. GERD patients with severe reflux esophagitis or complications such as peptic stricture or Barrett's esophagus should be maintained on proton pump inhibitors such as lansoprazole or omeprazole. For young and otherwise healthy patients, antireflux surgery is a viable option. Appended to the article is a discussion between the author and a panel of physicians. 2 figures. 3 tables. 35 references. (AA-M).

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Low-Dose Ranitidine for the Relief of Heartburn Source: Alimentary Pharmacology and Therapeutics. 13(4): 459-465. April 1999. 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: Approximately 30 percent of adults in the United States suffer from heartburn and related symptoms monthly; more than 20 percent of these people experience heartburn at least once per day. Although many rely on self medication with antacids for the relief of their symptoms, treatments that decrease gastric volume as well as increase the pH of refluxed material should be more effective in relieving heartburn.

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This article reports on a study undertaken to compare the safety and efficacy of low dose regimens of ranitidine for the relief of heartburn. Adults with at least a 3 month history of heartburn were eligible for this randomized, double blind, parallel group, multicenter dose ranging study. Following a 1 week open label run in phase to document baseline heartburn frequency, subjects were randomized to receive treatment with one tablet of either ranitidine 75 mg (n = 491), ranitidine 25 mg (n = 504), or placebo (n = 494), to be taken as needed up to four times daily for 2 weeks for the relief of heartburn. The ranitidine 75 mg (Zantac 75) regimen was clinically and statistically more effective than placebo for all measures in relieving heartburn and reducing antacid consumption. In addition, the ranitidine 75 mg regimen was superior to placebo in providing heartburn relief within 30 minutes of dosing that lasted for up to 12 hours. Ranitidine 25 mg was observed to be statistically superior but not clinically different from placebo, as defined a priori, in providing heartburn relief. All treatments were well tolerated and adverse events occurred no more frequently with the ranitidine regimens than with placebo. No clinically significant drug interactions with ranitidine were observed in this study. The authors note that the issue of drug interactions is especially important for products made available over the counter because of the potential for exposure to dangerous interactions that may occur in the absence of oversight by health care professionals. 1 figure. 1 table. 12 references. •

Photodynamic Therapy for Barrett's Esophagus Source: Gastrointestinal Endoscopy Clinics of North America. 7(2): 207-220. April 1997. Contact: Available from W.B. Saunders Company. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: Barrett's esophagus is characterized by replacement of normal esophageal mucosa with metaplastic columnar epithelium. Barrett's esophagus is common, occurring in an estimated 10 to 13 percent of patients with chronic gastroesophageal reflux disease (GERD), but its frequency may be up to 20 times higher. The mucosal change is believed to represent the result of the body's defensive mechanism to protect the esophagus against repeated acid or bile reflux. Barrett's esophagus is associated with an increased occurrence of mucosal dysplasia and adenocarcinoma in the specialized glandular mucosa. In this article, the authors describe their results using photodynamic therapy (PDT) in 55 patients with Barrett's esophagus and dysplasia or superficial cancer. Patients were followed for 6 to 66 months following PDT. All patients were maintained on longterm omeprazole to achieve acid suppression to allow mucosal repair in an antacid environment. Extensive mucosal ablation was observed after PDT. Followup endoscopic findings and biopsies demonstrated a reduction in the extent of Barrett's mucosa in all patients with replacement of an estimated 75 to 80 percent of the treated mucosa by squamous epithelium. Dysplasia was eliminated in 42 of the 55 patients. Esophageal strictures occurred in 53 percent of patients, but were treated satisfactorily with dilation. The authors conclude that PDT offers an alternative nonsurgical therapy that eliminates dysplasia and superficial cancer and reduces Barrett's mucosa while reducing risks and costs. 1 figure. 2 tables. 54 references. (AA-M).

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Esophageal Cancer and Barrett's Esophagus: How to Approach Surveillance, Treatment and Palliation Source: Postgraduate Medicine. 105(7): 111-114, 119-122, 125-127. June 1999. Summary: Despite the technologic advances of modern medicine, esophageal cancer remains a deadly and challenging disease. Treatment success depends on identifying

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cancer early in its course or preventing Barrett's esophagus from progressing to cancer. However, this goal is hampered by the fact that disease is often advanced by the time symptoms appear. In this article, the second in a series of three on esophageal diseases, the authors discuss squamous cell carcinoma, adenocarcinoma, and its precursor lesion, Barrett's esophagus. The authors describe factors that increase patients' risk and steps to take if one of the conditions is detected. The most important risk factors for squamous cell cancer are a history of prolonged use of tobacco or alcohol, a history of ingestion of a caustic substance, nutritional deficiencies, or chronic esophagitis. In addition to a strong association between adenocarcinoma and Barrett's esophagus, the risk of adenocarcioma is increased with obesity, smoking, heartburn, and middle age. Barrett's esophagus is the most important predisposing factor for adenocarcinoma of the esophagus. Once considered a rare congenital disorder, it is now recognized to be a relatively common acquired condition, or special form of healing, that develops as a consequence of gastroesophageal reflux disease (GERD). In patients with Barrett's esophagus without dysplasia, treatment of reflux (usually with proton pump inhibitors) should be undertaken to heal inflammation and control symptoms. The authors conclude that reducing mortality from esophageal cancer requires either early identification of patients or prevention of progression from Barrett's esophagus to cancer. 7 figures. 2 tables. 29 references. •

Roundtable: The Serious Side of Gastroesophageal Reflux Disease Source: Practical Gastroenterology. 22(8): 40, 42-44, 46-48, 50. August 1998. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: During the 1998 Digestive Disease Week Conference held in New Orleans, a special roundtable was convened at which three leading gastroenterologists challenged their fellow physicians to treat the heartburn-like symptoms of gastroesophageal reflux disease (GERD) seriously. This article presents a transcript of that roundtable. The first speaker notes that many GERD or heartburn sufferers live uncomfortably because of their symptoms. Patients may self diagnose, dismissing symptoms and ignoring a condition that can potentially lead to more serious problems. The authors review the esophageal complications of GERD, including esophageal ulceration, stricturing, or Barrett's esophagus. Barrett's esophagus can progress to adenocarcinoma of the esophagus. One of the panelists discusses the impact of GERD on a patient's quality of life by reporting results from a survey of patients with GERD. Sixty-five percent of these people reported that their heartburn interrupted their sleep; 21 percent reported delaying an assignment or project at work; 20 percent reported leaving work early, working at home, or calling in sick specifically because of their heartburn; 15 percent reported canceling plans with friends or family because of GERD; and 9 percent reported interference with their sex lives. The article also discusses chronic laryngitis, reflux laryngitis, symptoms of GERD, including chest pains and asthma, and the use of the proton pump inhibitor to treat heartburn.

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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/.

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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 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. •

Gastroesophageal Reflux Disease in Minority America Source: Practical Gastroenterology. 26(2): 35, 38, 40-41, 45. February 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Gastroesophageal reflux disease (GERD) is one of the most common diseases presently seen in American clinical practice. The vast majority of research in the U.S. for GERD has evaluated non-Hispanic whites or a multiethnic group with obvious biases. This article explores GERD in minority America. The author notes that minimal information exists regarding GERD in the minority groups (African, Asian, Hispanic, and Native Americans) of the nation. Available data indicates the following: African Americans have a decreased prevalence of GERD and Barrett's esophagus and Hispanic Americans have a similar prevalence of Barrett's esophagus as in non Hispanic whites. No data exists for GERD in either Asian or Native Americans. Further investigation regarding the prevalence, severity, esophageal function or dysfunction, clinical presentation, and treatment outcome of GERD in minority groups needs to be performed in order to provide the maximum benefit for all Americans with this disease. 1 table. 24 references.

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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

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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. •

Surgical Treatment for Gastroesophageal Reflux Disease Source: Practical Gastroenterology. 24(11): 11-12, 14, 17-18. November 2000. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Patients with gastroesophageal reflux disease (GERD) can usually be effectively treated using antacids, H2 blockers, or proton pump inhibitors. Symptoms often recur after cessation of medication and therefore many patients require lifelong medication. Some patients do not want to be dependent on medications for the rest of their lives and some fail to obtain permanent relief of symptoms or develop complications of their disease. In these cases, an alternative therapy may be offered. This article explores the use of surgical treatment for GERD. The authors note that in the past there was a reluctance to recommend antireflux surgery due to the uncertainty of the outcome and the magnitude of the surgical approach. Surgery aims to create a barrier to reflux (return) of gastric and duodenal content across the lower esophageal sphincter (LES) into the esophagus. Surgery can also reduce the hiatal hernia, and accelerate gastric emptying. The ability to do these operations using minimally invasive techniques has changed the treatment options for GERD patients. The first report of the laparascopic approach for antireflux surgery was published in 1991. Since there, there has been a rapid increase in the demand for antireflux surgery, both by patients and gastroenterologists. However, the authors caution that the availability of laparoscopic surgical therapy for GERD should not lessen the indications for surgery, and patients should be fully aware of the potential postoperative morbidity and mortality. 2 figures. 14 references.

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Long-Term Outcome of Medical and Surgical Therapies for Gastroesophageal Reflux Disease: Follow-Up of A Randomized Controlled Trial Source: JAMA. Journal of the American Medical Association. 285(18): 2331-2338. May 9, 2001. Summary: Severe gastroesophageal reflux disease (GERD) is a lifelong problem that can be complicated by peptic esophageal stricture and adenocarcinoma of the esophagus. This article reports on a study undertaken to determine the long term outcome of medical and surgical therapies for GERD. The followup study was conducted between October 1997 and October 1999, of the medical and surgical antireflux treatments in patients with complicated GERD. Mean duration of followup was 10.6 years (median 7.3 years) for medical patients and 9.1 years (median 6.3 years)

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for surgical patients. Of the original 247 study patients, 239 (97 percent) were located (79 were confirmed dead). Among the 160 survivors (157 men and 3 women), 129 patients (including 91 in the medical treatment group and 38 in the surgical treatment group) participated in the followup. Eighty-three (92 percent) of 90 medical patients and 23 (62 percent) of 37 surgical patients reported that they used antireflux medications regularly. During a 1 week period after discontinuation of medication, mean symptom scores were significantly lower in the surgical treatment group. However, no significant differences between the groups were found in grades of esophagitis, frequency of treatment of esophageal stricture, and subsequent antireflux operations, physical and mental component scale scores, and overall satisfaction with antireflux therapy. Survival during a period of 140 months was decreased significantly in the surgical versus the medical treatment group, largely because of excess deaths from heart disease. Patients with Barrett esophagus at baseline developed esophageal adenocarcinomas (cancer) at an annual rate of 0.4 percent, whereas these cancers developed in patients without Barrett esophagus at an annual rate of only 0.07 percent. There was no significant difference between groups in incidence of esophageal cancer. The authors conclude that antireflux surgery should not be advised with the expectation that patients with GERD will no longer need to take antisecretory medications or that the procedure will prevent esophageal cancer among those with GERD and Barrett esophagus. 1 figure. 3 tables. 46 references. •

Long-Term Omeprazole Treatment in Resistant Gastroesophageal Reflux Disease: Efficacy, Safety, and Influence on Gastric Mucosa Source: Gastroenterology. 118(4): 661-669. April 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The efficacy and safety of long term acid suppression (to treat recurrent gastroesophageal reflux disease, or GERD) remains a subject for debate. This article reports on a study of patients refractory reflux esophagitis who were undergoing maintenance therapy with a regimen of greater than 20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4 to 11.2 years). Patients with severe reflux esophagitis resistant to long term therapy with H2 receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus (the base of the stomach). In 230 patients (mean age, 63 years at entry; 36 percent were older than 70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori positive and negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7 percent in H. pylori positive patients and 0.7 percent in H. Pylori negative patients, which was mainly observed in elderly patients who had moderate or severe gastritis at entry. In patients with baseline moderate or severe gastritis, the incidences were similar: 7.9 percent and 8.4 percent, respectively. Corpus intestinal metaplasia was rare, and non dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. The authors conclude that long term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis. 3 figures. 3 tables. 40 references.

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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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Gastroesophageal Reflux Disease in Elderly Source: Practical Gastroenterology. 26 (5): 13-14, 16, 19-20, 22-23, 27-29. May 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: The high incidence of hiatal hernia in the geriatric population is among the many causes that promotes gastroesophageal reflux (the return of stomach acid to the esophagus) and is an important basis for severe and complicated esophagitis. Several medications consumed by the elderly for comorbid (present at the same time) conditions may make reflux disease worse. Older subjects often underreport reflux symptoms with the physician tending to overlook gastroesophageal reflux disease (GERD) as less important compared to more serious diseases from which the patients may suffer. In this review article, the authors present the age-related anatomic and functional alterations in the upper gastrointestinal tract that predispose patients to reflux. The authors also discuss the current strategies in management. 2 tables. 63 references.

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Prevalence of Barrett's Esophagus in Asymptomatic Individuals Source: Gastroenterology. 123(2): 461-467. August 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: The incidence of esophageal adenocarcinoma (cancer) in the western world has been linked to chronic heartburn, regurgitation, and the development of the premalignant epithelium of Barrett's esophagus (BE). However, up to 40 percent of esophageal adenocarcinomas occur in patients without prior reflux symptoms. This article reports on a study in which the authors prospectively screened for the presence of BE in asymptomatic subjects older than 50 years of age undergoing screening sigmoidoscopy for colorectal cancer. Of 408 potential study candidates, 110 subjects were screened; 9 were women. The mean age was 61 years, plus or minus 9.3 years; most of the population (73 percent) was Caucasian. Intestinal metaplasia (IM) extending

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above the esophagogastric junction (EGJ) was detected in 27 subjects (25 percent); 8 patients (7 percent) had long segment BE and 19 (17 percent) had short segment BE. Patients with BE were no more likely to be obese, consumers of tobacco or alcohol, report a family history of gastroesophageal reflux disease (GERD), show association with toxic exposure, or use antacids more than once a month, compared with those without BE. BE was detected in 25 percent of asymptomatic male veterans older than 50 years of age undergoing screening sigmoidoscopy for colorectal cancer. 1 figure. 3 tables. 30 references. •

Benefits and Risks of Exercise: From Heart-Healthy to Heartburn Source: Digestive Health and Nutrition. p. 12-14. March/April 2004. Summary: The overall benefits of exercise are outstanding, however physical activity may be responsible for flare-ups of some gastrointestinal diseases. This article explores the benefits and risks of exercise, focusing on gastroesophageal reflux disease (GERD), gastrointestinal bleeding, ulcers, inflammatory bowel disease (IBD), and colorectal cancer. For each condition, the author outlines symptoms to watch for, strategies to prevent complications, and risk factors. The author encourages readers to incorporate physical activity into their everyday lifestyle, perhaps with preventive medicine or less vigorous workouts, if necessary. 1 figure. 3 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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Quality of Life Implications of Medical and Surgical Treatment of Gastroesophageal Reflux Disease Source: Practical Gastroenterology. 24(7): 26, 28, 30, 32. July 2000. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435.

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Summary: This article considers the quality of life (QOL) implications of the medical and surgical treatment of gastroesophageal reflux disease (GERD). The author begins with a brief review of the QOL assessment instruments in common use, including generic, disease specific, and symptom severity questionnaires. QOL instruments can be assessed on five counts: reliability, validity, sensitivity to changes (also known as responsiveness), appropriateness, and practicality. The author stresses that GERD has a profound effect on the QOL in patients with the disease. The author reviews studies of the effects of medical therapy (drugs) and surgical therapy on patients with GERD and concludes that it would be impossible to make a standardized treatment policy for all patients (because QOL is such a complex issue). Nevertheless, the author concludes that it is clear that most patients do not require an initial extensive evaluation using expensive physiologic testing, such as esophageal manometry or 24 hour pH monitoring. It is reasonable to direct patients with severe or intractable symptoms, patients who are young, or patients who simply do not like taking medications toward surgery. Patients with minimal symptoms that can be managed with either lifestyle changes or inexpensive antisecretory drugs, patients who are older, or patients who are not surgical candidates should be directed toward maintenance drug therapy. Patients with Barrett's metaplasia (changes in the cells of the esophagus, considered a precancerous condition) must be maximally medically treated or can be considered surgical candidates. In these patients, routine endoscopic screening to detect progression to high grade dysplasia or carcinoma is mandatory. 13 references. •

Oral and Pharyngeal Complications of Gastroesophageal Reflux Disease: Globus, Dental Erosions, Chronic Sinusitis Source: Journal of Clinical Gastroenterology. 30(3 Supplement): S35-S38. April 2000. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This article describes the oral and pharyngeal manifestations of gastroesophageal reflux disease (GERD), which are most likely caused by physical contact of regurgitation of gastric content with surface mucosa and as such suggests abnormalities of the airway protective mechanisms. The authors caution that the body of evidence on the causation, and therefore the diagnosis and treatment of these increasingly diagnosed disorders is still evolving. The lack of a clear cause and effect relationship is complicated by the fact that patients with suspected supraesophageal complications of reflux disease frequently lack the characteristic features of esophageal peptic injury, including the most typical symptom of heartburn. These problems often recur, but are usually susceptible to empiric antireflux treatment (for example, with proton pump inhibitors). A detailed patient history may provide important clues to the association of acid reflux and suspected supraesophageal complications. A history of regurgitation, particularly at nighttime, associated with cough or with symptoms suggesting aspiration is a most significant clue to the possibility of supraesophageal complications of GERD. A history of repetitive throat clearing, recurrent hoarseness (particularly in the morning), halitosis (bad breath), or hypersialorrhea (excessive saliva) should also alert the clinician to the possibility of an acid reflux related supraesophageal condition. However, the majority of patients with this condition may have no esophageal symptoms at all. The authors discuss globus pharyngeus, chronic sinusitis, and gastroesophageal reflux and dental erosions, as other possible symptoms. 2 tables. 37 symptoms.

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Prevention and Treatment of Dysplasia in Gastroesophageal Reflux Disease: The Results and the Challenges Ahead Source: Journal of Gastroenterology and Hepatology. 17 (Supplement): S113-S124. February 2002. 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 article discusses dysplasia (abnormal tissue growth) in gastroesophageal reflux disease (GERD) that arises in a setting of Barrett's esophagus. The author notes that since the last World Congress of Gastroenterology there has been an explosion of interest in Barrett's esophagus. The goal of interventions designed to prevent, detect, or treat GERD associated Dysplasia is to attenuate or eliminate the risk of progression to cancer. To do so, the subset of GERD patients with Barrett's esophagus must first be identified. Barrett's esophagus may affect over 1 percent of the North American population, but many more millions than that have chronic GERD. This review article focuses on the advances in treatment and on the challenges ahead for those individuals with known Barrett's esophagus. However, it is sobering to note at the outset that the current best efforts may have limited impact on morbidity and mortality from Barrett's related cancer in the population. For example, in a recent systematic review of published surgical cohort studies, the authors found that only 5 percent of patients reported to have undergone resection of esophageal adenocarcinoma (cancer) were known to have a prior diagnosis of Barrett's and were thus potentially eligible for surveillance. The best case scenario begins with cost-effective and healtheffective strategies being developed to screen GERD patients to identify all who have Barrett's esophagus. 3 tables. 61 references.

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Gastroesophageal Reflux Disease: Long-Term Management Strategies Source: Consultant. 37(7): 1833-1837, 1840, 1843-1844. July 1997. Contact: Available from Consultant. Cliggott Publishing Company, 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article discusses long term management strategies to be used for patients with gastroesophageal reflux disease (GERD). The author examines data from recent trials and extrapolates specific management recommendations, focusing on the safety of long term therapy. For maintenance therapy in patients with moderate or severe GERD, a proton pump inhibitor should be used, such as 20 mg per day of omeprazole or 30 mg per day of lansoprazole. Long term H2 blocker therapy is appropriate only for patients with mild disease. Aggressive proton pump inhibitor therapy may prevent esophageal strictures and may heal mucosal damage associated with Barrett's esophagus. Cisapride may be an alternative in patients with mild disease, particularly those with symptoms that suggest dysmotility. Sucralfate may be best for patients who have bile reflux and alkaline esophagitis or prominent bile reflux-tryptic esophagitis, such as may be seen with a Billroth II hemigastrectomy. As a general principle, reserve combination therapy with a proton pump inhibitor and a prokinetic agent for patients with severe dysmotility syndromes, such as scleroderma or gastroparesis associated with diabetes. 2 figures. 2 tables. 36 references. (AA-M).

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Barrett's Esophagus: Treatment with 5-Aminolevulinic Acid Photodynamic Therapy Source: Gastrointestinal Endoscopy Clinics of North America. 10(3): 421-437. July 2000.

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Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article discusses the management of patients with metaplastic (cell changes) and in particular dysplastic (cell changes indicative of cancer or precancer) Barrett's esophagus. The lower esophagus is normally lined with squamous mucosa. Under certain conditions of gastroesophageal reflux (the return of the stomach's gastric acid into the esophagus), this is replaced with a metaplastic columnar epithelium, also called Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal cancer. The author stresses that there is an urgent need for minimally invasive methods that eradicate the abnormal mucosa associated with high grade dysplasia, but that do not cause the high rates of morbidity and mortality associated with esphagectomy (removal of part or all of the esophagus). The author proposes the use of 5 aminolevulinic acid (ALA) photodynamic therapy (PDT) as a method for ablation for Barrett's epithelium. The author covers the mechanism of this technique; specificity of tissue localization following ALA administration; dosimetric considerations for this type of PDT; the tissue pharmacokinetics of 5ALA induced protoporphyrin IX accumulation in Barrett's esophagus; the methods of treatment, including photosensitizer administration and light irradiation; and patient selection and management considerations. The author concludes by emphasizing the need for ongoing patient surveillance after these PDT methods, as they may not reverse the biologic progression of the dysplasia (of the cells remaining after the ablation). 6 figures. 39 references. •

Photodynamic Therapy of Barrett's Esophagus Source: Gastrointestinal Endoscopy Clinics of North America. 10(3): 409-419. July 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article discusses the use of photodynamic therapy for patients with Barrett's esophagus. The lower esophagus is normally lined with squamous mucosa. Under certain conditions of gastroesophageal reflux (the return of the stomach's gastric acid into the esophagus), this is replaced with a metaplastic columnar epithelium, also called Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal cancer. Unfortunately, the treatment for Barrett's esophagus (removal of part or all of the esophagus) is complex and dangerous. Photodynamic therapy uses endoscopic therapies to eliminate metaplastic mucosa (cancer or precancer cells) and allow repopulation of the surface of the esophageal lining with normal squamous mucosa. This treatment is designed to decrease the risk of cancer development. The authors discuss acid suppression, photosensitizers in photodynamic therapy, lasers and photodynamic therapy, photoradiation devices, tissues effects of photodynamic therapy, and clinical results. The authors conclude that photodynamic therapy seems able to control high grade dysplasia within Barrett's esophagus about 80 percent of the time. Long term results are not yet available, but the treatment is promising. Given the success with surgical intervention, however, use of photodynamic therapy should be reserved for nonsurgical candidates at the current time. The complications that occur with photodynamic therapy are not trivial and must be weighed against the potential benefits. Cutaneous photosensitivity, chest pain, nausea, and stricture formation all may occur. Improved dosimetry is needed to decrease these problems. 1 table. 27 references.

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Chest Pain and Gastroesophageal Reflux Disease Source: Journal of Clinical Gastroenterology. 30(3 Supplement): S39-S41. April 2000.

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Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This article explores the diagnosis of gastroesophageal reflux disease (GERD), in patients with chest pain. GERD is the most common gastrointestinal cause of noncardiac chest pain. The author begins by discussing diagnostic issues, noting that following exclusion of a cardiac cause of the patient's chest pain, an evaluation of the esophagus is most appropriate. Barium studies, endoscopy, and esophageal manometry have little value in the diagnosis of GERD induced chest pain. Twenty-four hour pH monitoring with a symptom index correction may define an association but does not prove causality between the patient's chest pain and GERD. Recent studies have implied that high dose proton pump inhibitor (PPI) therapy for one week is an effective approach. The PPI test has excellent sensitivity and specificity and economic savings (due to a reduction in diagnostic procedures). Therefore, the PPI test should be the diagnostic or therapeutic approach of choice for patients with suspected GERD induced chest pain. 1 figure. 10 references. •

Gastroesophageal Reflux Disease: Under the Surface of Heartburn Lies a Potentially Serious Disease Source: AJN. American Journal of Nursing. 100(9): 24D, 24F, 24H. September 2000. Contact: Available from Lippincott Williams and Wilkins. AJN, P.O. Box 50480, Boulder, CO 80322-0480. (800) 627-0484 or (303) 604-1464. Summary: This article familiarizes nurses with gastroesophageal reflux disease (GERD), a potentially serious disease that can be the cause of many patient's symptoms of heartburn. Heartburn is the most common symptom of GERD, which is caused by a weakened or inappropriately relaxed lower esophageal sphincter (the ring of muscle between the stomach and the esophagus). GERD is the most prevalent of the acid related disorders, which also include dyspepsia, gastritis, and peptic ulcer disease. The primary symptom of GERD is heartburn, which typically occur two to three hours after ingestion of a large or fatty meal or when lying down. When the gastric acid is in contact with the esophagus repeatedly or for long periods of time, the esophagus can become damaged and irritated; this can also cause the development of precancerous cells. A careful history can help differentiate between cardiac chest pain, panic attacks, other sources of esophagitis, and GERD. Diagnostic tests can include barium swallow test, esophageal manometry or esophageal pH, esophagoscopy, and the Bernstein test. These diagnostic studies assess esophageal motility (movement of contents through the esophagus), clearance, and the causes of gastroesophageal reflux. Treatment goals for patients with GERD are to eliminate the symptoms, decrease the reflux, and make the refluxed material less irritating to the esophagus. Treatment includes dietary and lifestyle changes, drug therapy, and sometimes surgery. 1 figure. 15 references.

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Pathophysiology of Gastroesophageal Reflux Disease: The Role of the Lower Esophageal Sphincter Source: Practical Gastroenterology. 23(11): 19-20, 27-28, 30, 32-34. November 1999. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article focuses on the role of the lower esophageal sphincter (LES) in the pathophysiology of gastroesphageal reflux disease (GERD). The author reports that recent studies have confirmed that there are not one but two LESs. The dual sphincter

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mechanism at the esophagogastric junction (EGJ) is composed of intrinsic smooth muscles of the LES (internal LES) and skeletal muscles of the crural diaphragm (external LES). Other anatomical structures at the lower end of the esophagus may also play a role as antireflux barriers, but their exact function is not clear. The author explores LES pressure under various physiologic conditions, including links with respiration, exercise, and physical conditions that increase intraabdominal pressure. Other topics include the neural control of the internal and external LES, the physiologic significance of the two LESs, the mechanisms of gastroesophageal reflux, transient LES relaxation, stimuli that trigger transient LES relaxations (gastric distension, pharyngeal mechanisms, and neural causes), the effect of antireflux therapy on transient LES relaxation, LES hypotension in reflux disease, and the role of hiatal hernia in the induction of gastroesophageal reflux. The author comes up with a unifying hypothesis for the pathogenesis of reflux disease. The initial pathologic event is most likely frequent transient LES relaxations and the corresponding acid reflux episodes. Acid in the esophagus then causes esophagitis, which leads to a low internal LES pressure and esophageal hypotension. Furthermore, esophagitis induces esophageal shortening through acid induced contraction of the longitudinal muscles. Subsequent fibrosis may develop, resulting in a hiatus hernia. 3 figures. 19 references. •

Overview of the Clinical Spectrum of Gastroesophageal Reflux Disease Source: Practical Gastroenterology. 23(10): 43, 48, 57-58, 60, 62. October 1999. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article is the first in a series offering an indepth review of the pathophysiology, clinical presentation, diagnosis, and therapy of gastroesophageal reflux disease (GERD). The author of this overview of the clinical spectrum of GERD notes that the acronym GERD has become popular to describe all of the clinical manifestations of gastroesophageal reflux disease, including the various symptoms and forms of tissue damage that occur secondary to the reflux of gastric contents into the distal esophagus. Presentations of GERD vary widely; the author discusses them in three different categories that comprise the spectrum of GERD: typical symptoms, atypical symptoms, and complications. The author notes that mild postprandial (after a meal) reflux occurring in normal people that does not cause symptoms or esophageal mucosal injury is called physiologic reflux. The author then discusses the prevalence of GERD, the relationships between symptoms and meals (particularly certain foods), the diagnostic evaluation of the patient with GERD (including barium radiography, endoscopy, intraesophageal pH monitoring), and the role of the hiatal hernia. Patients with a normal lower esophageal sphincter (LES) pressure tended to experience heartburn only after consuming certain foods including fried foods, spicy foods, and hot dogs, whereas those patients with a very low LES pressure experienced reflux symptoms with most types of foods. Recent information indicates that hiatal hernias may contribute to the severity of GERD by trapping acid in the hernial sac, thus becoming more available to reflux during LES relaxation. 3 figures. 20 references.

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Barrett's Esophagus: Put Guidelines into Practice Source: Patient Care for the Nurse Practitioner. 2(9): 23-24, 26. September 1999. Contact: Available from Medical Economics Company. Subscriber Services Department, Patient Care for the Nurse Practitioner, P.O. Box 3000, Denville, NJ 07834-9662. (800) 432-4570.

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Summary: This article offers guidelines for nurse practitioners managing the patient with Barrett's esophagus, a premalignant lesion for adenocarcinoma of the esophagus. The condition develops in 10 to 15 percent of patients with longstanding symptomatic gastroesophageal reflux disease (GERD), with white men approximately 60 years of age and older being at highest risk. The author first provides a clinical overview of the disease, noting that the definition of Barrett's esophagus has undergone a significant change over the past decade. Confirmation of the diagnosis requires that multiple biopsies be obtained from the columnar lining of the esophagus. The goals of therapy in patients with Barrett's esophagus are similar to those in patients with chronic reflux symptoms: to control symptoms and heal the esophageal mucosa. Control of symptoms in these patients may require higher than normal dosages of a proton pump inhibitor (PPI). Because patients with Barrett's esophagus have a 30 to 120 fold increased risk for esophageal cancer, surveillance to detect dysplasia (changes in cell structure) and adenocarcinoma is indicated. Data suggest that esophageal cancer in Barrett's esophagus detected during routine surveillance has a more favorable prognosis than carcinoma detected when the patient is already symptomatic with dysphagia (swallowing difficulties). The author concludes by briefly reviewing the nonsurgical options for patients with early adenocarcinoma or high grade dysplasia. 1 figure. 10 references. •

Treatment of Mild to Moderate Gastroesophageal Reflux Disease Source: Practical Gastroenterology. 21(4): 46, 48-50, 52-53. April 1997. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article outlines the treatment of mild to moderate gastroesophageal reflux disease (GERD), a common disorder seen by physicians across many specialties. At least 10 percent of the U.S population have daily heartburn symptoms, while countless others have less frequent symptoms. Management of symptoms in patients with mild to moderate GERD without erosive esophagitis requires a systematic approach beginning with lifestyle modification and over the counter H2 antagonists and or antacids. This can proceed as required to prescription pharmacologic management with H2 antagonists, prokinetic agents, and or proton pump inhibitors. The efficacy, safety, and costs of the available therapeutic alternatives must be considered in choosing acute and longterm therapy. In addition, the appropriate use of endoscopy and other diagnostic tests is important in establishing a diagnosis of nonerosive mild GERD. The authors stress that both acute and longterm management must be individualized on the basis of symptom presentation, augmented when needed by findings of endoscopy and ambulatory pH monitoring. 4 tables. 11 references. (AA-M).

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When Heartburn Turns Serious Source: Digestive Health and Nutrition. 4(3): 18-21. May-June 2002. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: This article provides information about heartburn and the complications that can arise when heartburn becomes chronic. Heartburn is the most common symptom of gastroesophageal reflux disease (GERD), a condition in which gastric (stomach) acid returns back to the esophagus, causing pain. The author reviews the role of the lower esophageal sphincter (LES), the valve between the esophagus and the stomach. The

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article discusses heart pain (cardiac pain) versus heartburn, the role of heartburn in asthma, heartburn as a risk factor for Barrett's esophagus and esophageal cancer, monitoring and treatment strategies, controlling heartburn symptoms through lifestyle changes, when to seek medical treatment, and new therapies for heartburn that are currently in the research stage. The author stresses that it is important to remember that frequent heartburn is a symptom of a disease, not just a lifestyle inconvenience. The article concludes with a list of four websites with additional information about heartburn. •

Patient Characteristics and Lifestyle Recommendations in the Treatment of Gastroesophageal Reflux Disease Source: Journal of Family Practice. 44(3): 266-272. March 1997. Summary: This article reports on a study to describe the patient-reported frequency with which health care providers recommend lifestyle changes to patients with gastroesophageal reflux disease (GERD). The study looked at patient characteristics, including sex, age, body mass index (BMI), tobacco use, alcohol use, type of health insurance, and clinical location (rural versus urban). The first 50 patients enrolled in a prospective quality of life study of patients with GERD were used as the sample population. Telephone surveys administered immediately following the diagnosis of GERD included seven specific questions on lifestyle modifications that may have been recommended by primary health care providers during the clinic visit. Five of seven (71 percent) lifestyle modification recommendations were reported by less than 50 percent of patients as being received from health care providers. Patients aged 60 years or older were less likely to report receiving recommendations than those younger than 60 years. Patients with a BMI greater than 30 were more likely to report receiving eating-related recommendations. Heavier smokers were more likely to report receiving recommendations than lighter smokers. The authors conclude that, based on patient report, health care providers recommended lifestyle modifications to a modest percentage of patients with GERD and modified counseling for specific patient characteristics, such as age, BMI, smoking, and alcohol consumption. The authors call for additional prospective research, using physician report and observation, as well as patient report, and using more numerous patient cohorts. 2 tables. 47 references. (AAM).

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Conversions and Complications of Laparoscopic Treatment of Gastroesophageal Reflux Disease Source: Journal of the American College of Surgeons. 189(4): 356-361. October 1999. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866. Summary: This article reports on a study undertaken to determine the rate of conversions (to open surgery) and complications of the laparoscopic treatment of gastroesopheageal reflux disease (GERD). The authors retrospectively reviewed the protocol sheets of 503 consecutive patients with GERD who underwent laparoscopic fundoplication over a period of 5 years. A Nissen Rosetti procedure was performed in 492 patients (97.8 percent) and a Toupet procedure in 11 patients (2.2 percent). Sixty four patients were also subjected to a concurrent cholecystectomy (gallbladder removal), and one patient had concurrent esophageal surgery. Thirty one patients had previous upper abdominal operations. The period of hospitalization varied from 12 hours to 16 days, with an average of 1.2 days. The operation was converted to an open procedure in 10

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patients (2 percent). The main cause of conversion was the presence of adhesions. The most frequent intraoperative complication was pneumothorax. All pneumothoraces occurred in the first 100 patients. Five patients had significant operative bleeding; two of them required laparotomy for bleeding control. Gastric ulcer was diagnosed in six patients. One alcoholic patient died of acute pancreatitis. Other major complications were two intra abdominal abscesses, one esophageal perforation, one sepsis from gastric perforation, one hemorrhagic shock, and one gastric obstruction from fundoplication herniation. The authors conclude that conversions and complications of laparoscopic fundoplication are low and decrease significantly with the surgeon experience, but severe and lethal complications may occur. 1 figure. 2 tables. 22 references. •

Dousing Your Heartburn Source: Healthline. p. 15. November-December 2000. Contact: Available from Sickbay Health Media, Inc. Healthline, 510 Broadhollow Road, Suite 300, Belville, NY 11747. (631) 694-0040. Fax (631) 694-2234. Website: www.healthline.com. Summary: This article reviews strategies to treat 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). Frequent heartburn is called gastroesophageal reflux disease (GERD); people with GERD may also experience nausea, sore throat, hoarseness, wheezing, and a cough. The article reviews the causes and incidence of gastroesophageal reflux disease (GERD), and summarizes the levels of treatment. Risk factors for GERD include being over 65 years of age, use of certain medications, obesity, pregnancy, a high fat diet, and use of caffeine, alcohol, or tobacco. Most people with GERD have a mild disease and a low risk for long term complications. However, untreated, GERD can lead to inflammation of the esophagus (esophagitis) or to a precancerous condition called Barrett's esophagus. The article focuses on behavioral strategies to help prevent heartburn: control weight, avoid foods or beverages that can trigger heartburn, minimize fat in the diet, avoid lying down for 2 hours after eating, do not smoke, and do not drink alcohol. Drug therapy can include nonprescription drugs such as antacids and H2 blockers, then prescription medications such as stronger H2 blockers and proton pump inhibitors. Finally, surgery to improve the functioning of the muscular valve between the stomach and the esophagus may be required in the worst cases.

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Biology of Gastroesophageal Reflux Disease: Pathophysiology Relating to Medical and Surgical Treatment Source: in Coggins, C.H., ed. Annual Review of Medicine: Selected Topics in the Clinical Sciences. Palo Alto, CA: Annual Reviews. 1999. p. 469-506. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org. PRICE: $60.00 plus shipping and handling. ISBN: 0824305507. Summary: This article reviews the biology of gastroesophageal reflux disease (GERD), relating pathophysiology to medical and surgical therapy. The authors present various definitions of the disease and then develop workable criteria to identify patients with the disease. The central importance of the lower esophageal high pressure zone as a barrier to reflux is emphasized, along with an analysis of its biomechanical alteration in

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disease. The authors discuss the composition of the refluxed gastric juice in regard to its potential for mucosal injury. They provide evidence that cardiac type mucosa is an acquired sequel to acid induced squamous mucosal injury in the terminal esophagus. The authors propose a hypothesis that GERD begins in the stomach. Fundic distention occurs because of overeating and delayed gastric emptying secondary to the high fat Western diet. The distention causes the sphincter to be taken up by the expanding fundus, exposing the squamous epithelium of the terminal esophagus to gastric juice. Repeated exposure causes inflammation of the squamous epithelium, the formation of cardiac type mucosa, and carditis. The authors offer practical concepts regarding the treatment of GERD, based on a review of studies on the natural history of the disease and the long term outcome of therapy. 16 figures. 2 tables. 110 references. •

Gastroesophageal Reflux Disease: Short-Term Management Strategies Source: Consultant. 37(5): 1329-1330, 1335-1336, 1339-1340, 1346, 1348. August 1997. Contact: Available from Consultant. Cliggott Publishing Company, 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article reviews the factors that contribute to gastroesophageal reflux disease (GERD) and discusses intervention strategies for short term management. Dietary and lifestyle changes that may alleviate symptoms in patients with mild GERD include weight loss, elevating the head of the bed, avoiding postprandial recumbency (lying down after meals), and avoiding certain food and beverages (such as alcohol, fatty foods, coffee, onions, chocolate, and peppermint), and drugs that can contribute to the disorder (such as NSAIDs, alendronate, anticholinergics, sedatives, antiarrhythmics, quinidine, and potassium supplements). H2 receptor antagonists (given twice daily) are most effective in patients with nonerosive GERD; higher doses are necessary in patients with erosive esophagitis. Proton pump inhibitors have a longer duration of action than H2 receptor antagonists and are more effective in patients with moderate or severe GERD; an alternate day regimen may benefit some patients but is not appropriate for those with strictures or severe esophagitis. The author advises physicians to reserve combination therapy with a prokinetic agent and an H2 receptor antagonist or a proton pump inhibitor for patients who have severe underlying dysmotility syndromes. 2 figures. 3 tables. 12 references. (AA-M).

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Dyspepsia and Heartburn Source: Rheumatic Disease Clinics of North America. 25(3): 703-718. August 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article, from a series on the general medical care of the patient with rheumatic disease, reviews dyspepsia and heartburn. For each condition, the authors discuss a definition, epidemiology, causes, and management. The article includes two algorithms that illustrate a general approach to patients with dyspepsia and heartburn. The initial consultation should always include screening for alarm symptoms. If alarm symptoms are present, then the patient should be referred for an immediate endoscopy, regardless of whether the presenting symptom is dyspepsia or heartburn. In the absence of alarm symptoms, Helicobacter pylori status should be checked in patients with dyspepsia. If the patient is H. pylori negative, then an empiric course of treatment with a histamine H2 receptor antagonist can be tried for 4 to 6 weeks. Treatment can be alternated with prokinetic agents such as cisapride. If symptoms persist, then the patient should be referred for an endoscopy. If the patient is H. pylori positive, empiric

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antibiotic therapy should be instituted to reduce the ulcer pool. Patients who fail to respond or who have recurrence may have either persistent H. pylori infection (which can be confirmed by urea breath test) or another cause for their dyspepsia. These patients should then be considered for an endoscopy. In the absence of alarm symptoms, patients presenting with persistent heartburn should be given a trial of histamine H2 receptor antagonists, along with advice on lifestyle modifications. If symptoms do not respond, then proton pump inhibitors (PPIs) should be started. If the response continues to be suboptimal, the patient should be referred to a specialist for further workup, which can include endoscopy, a 24 hour ambulatory esophageal pH study to confirm gastroesophageal reflux disease or assess the degree of response to treatment, and esophageal manometry if scleroderma is suspected or surgery is contemplated. 2 figures. 106 references. •

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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Gastroesophageal Reflux Disease: Gaining Control Over Heartburn Source: Postgraduate Medicine. 101(2): 181-182, 185-187. February 1997. Summary: This is the first in a series of short articles on management of common complaints primary care physicians encounter in the office setting. In this article, the author focuses on gastroesophageal reflux disease (GERD). His article includes a summary of the current standard of care, a flowchart of the patient workup, and an information sheet that can be copied and distributed to patients. Topics include the etiology of GERD, symptoms, diagnosis, and drug therapy. Symptoms of reflux, such as heartburn, are due to a combination of factors: relaxation of the lower esophageal sphincter, hypersecretion of gastric acid, and resulting burning of the esophageal mucosa. Symptoms are usually classified as classic, atypical, or complicated. Treatment approaches include dietary and lifestyle changes, reduction of acidity with use of H2 receptor antagonists, and reduction of acid secretion with use of proton pump inhibitors. The author stresses that patient motivation is an important factor in the

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management of GERD. In rare instances, patients do not respond to medical treatment and are candidates for antireflux surgery. 1 figure. 1 table. 7 references. (AA-M). •

Interactions Between Helicobacter Pylori and Gastroesophageal Reflux Disease Source: Diseases of the Esophagus. 11(4): 203-209. October 1998. Contact: Available from Harcourt Brace and Company, Ltd. Journal Subscription Department. Foots Cray, Sidcup, Kent, DA 14 5HP. Summary: This literature review explores the relationship between Helicobacter pylori and gastroesophageal reflux disease (GERD). The authors begin by noting the differences in nomenclature, particularly between European and American researchers; European terminology is used in this article. The authors discuss the research articles and summarize their conclusions. H. pylori colonization rates do not differ between patients with uncomplicated GERD and controls. Eradication of H. pylori infection in patients with duodenal ulcer disease may provoke the development of reflux esophagitis. Cardiac mucosa is as susceptible to H. pylori infection as antral and corpus mucosa. An inflammatory cell response to infection in cardiac mucosa is similar to that observed in antral mucosa. In patients with Barrett's esophagus, H. pylori infects gastric epithelium but not intestinal epithelium. In patients without endoscopic Barrett's esophagus, intestinal metaplasia at the gastroesophageal junction may result from H. pylori infection. 2 tables. 72 references.

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Heartburn: When to Worry Source: Patient Care. 35(8): 40-42, 46-49. April 30, 2001. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: With the exception of situational heartburn, which is defined as occurring no more than once a month, the substernal (behind or under the breastbone) burning sensation many patients experience is always more than a minor symptom. At best, it characterizes gastroesophageal reflux disease (GERD), a chronic condition; at worst, it signals a premalignant condition or potentially fatal coronary disease. This article focuses on the serious complications of GERD rather than occasional heartburn. While antacides and lifestyle modifications are recommended early stage interventions, they are no substitute for prescription medications and possibly surgery in the face of severe esophagitis or Barrett's esophagus (BE). The authors note that lifestyle modifications definitely have a role in GERD therapy. However, the available medications can heal esophageal damage, prevent further damage from occurring, and significantly relieve the troubling symptoms associated with GERD. When patients present with heartburn, specific questions about the sensation experienced, what precipitates it, and the duration of the symptoms help pinpoint the diagnosis. Persistent extraesophageal symptoms such as asthma, cough, and noncardiac chest pain may be signs of GERD. Alarm symptoms such as dysphagia, odynophagia, weight loss, gastrointestinal (BI) bleeding, and anemia require immediate endoscopy. Patients with BE should be monitoring in a surveillance program for detecting early signs of malignancy. One table summarizes recommended dosages, indications, and side effects of medications commonly used to treat GERD. 1 figure. 1 table. 15 references.

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Federally Funded Research on Gastroesophageal Reflux Disease The U.S. Government supports a variety of research studies relating to gastroesophageal reflux disease. 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 gastroesophageal reflux disease. 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 gastroesophageal reflux disease. The following is typical of the type of information found when searching the CRISP database for gastroesophageal reflux disease: •

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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Project Title: ESOSPHAGUS

A

NOVEL

TECHNIQUE

FOR

SCREENING

BARRETT'S

Principal Investigator & Institution: Wang, Kenneth K.; Associate Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Gastroesophageal cancers are the most rapidly increasing cancer in Caucasian males and are a consequence of Barrett's esophagus. Barrett's esophagus is a pre-malignant condition that is produced by gastroesophageal reflux disease 2

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

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(heartburn). Screening for Barrett's esophagus can only be accomplished by endoscopy that is expensive and impractical given the population at risk. The purpose of this proposal is to design an "optical biopsy" system that can be applied by a wide range of health care providers to screen for Barrett's esophagus. This system will consist of an optical probe that can be placed into the esophagus with minimal discomfort to the patient that is connected to an optical biopsy console that will provide real time results. The primary design issues will be in constructing a small caliber probe that can be comfortably placed into the esophagus and yet expandable to provide contact with the esophageal wall for an optical biopsy. The second design consideration would be in constructing an algorithm that would analyze the spectroscopic signal from the "optical biopsy" which would distinguish normal and abnormal tissue in the upper gastrointestinal tract. Three proposed probe designs will be evaluated initially in the resected porcine esophagus and stomach to assess deployment of the probes and their safety. Subsequently, the probes will be assessed in the pig model to evaluate their performance characteristics. The best design will be selected for clinical testing. The clinical trials will involve the use of the probe in patients with known Barrett's esophagus and a control group undergoing endoscopy for other indications. The probe would be passed prior to endoscopy and the results compared to the endoscopic findings. The algorithms will be derived from optical and histological biopsies taken simultaneously at endoscopy from patients undergoing surveillance endoscopy for Barrett's esophagus. The development of a screening device for Barrett's esophagus that could be operated by paramedical personnel would enable large-scale low cost screening to identify patients at risk for esophageal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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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 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: APOPTOSIS IN BARRETTS METAPLASIA AND ESOPHAGEAL CANCER Principal Investigator & Institution: Hughes, Steven J.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The candidate is an academic gastrointestinal surgeon whose career objective is to become an independently funded clinician-scientist. He undertook a two-year research fellowship during surgical residency at the

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University of Michigan that provided preliminary experience in tumor biology and genetics, and instilled a strong desire to become a clinician scientist and an innovator in treatment of gastrointestinal malignancies. To develop his research career, the candidate needs significantly more time for scientific pursuits as well as the mentorship of experienced scientists. His career development plan includes both didactic and practical studies in the regulation of protein trafficking with the supervision of highly successful and innovative scientists at the University of Pittsburgh. The environment provided in the Department of Surgery is outstanding and has already trained numerous accomplished clinician-scientists. The sponsors have dedicated their laboratory resources, equipment, and time to ensure the candidate's success. The research plan focuses on improving our understanding of the cellular regulation of the death receptor Fas and differences in this regulation that may be important to the pathogenesis of Barrett's Esophagus (BE) and esophageal adenocarcinoma (EA). We have recently shown decreased cell surface expression of Fas in BE with dysplasia and EA suggesting alterations in Fas trafficking occur frequently and early in EA tumorigenesis. Surprisingly, very little is known about how cell-surface expression of Fas is regulated. We hypothesize that Fas protein degradation and trafficking of the receptor to and from the cell surface are important mechanisms of regulation, and that differences in this regulation exist between squamous esophageal epithelium and BE that contribute to the pathogenesis of BE and the associated risk of malignant transformation. To test these hypotheses, we propose two specific aims to examine Fas protein trafficking events and make comparisons of Fas expression and response to various stimuli in an immortalized esophageal epithelial cell line (HET-1A), primary cultures of esophageal squamous epithelium and BE, and EA cell lines (Seg-1, Bic-1, and Flo-1). Aim 1: To determine the cellular mechanisms involved in the regulation of Fas protein delivery to the cell surface in esophageal epithelia and adenocarcinoma cells. Aim 2: To determine the cellular mechanisms involved in the regulation of Fas protein stability at the cell surface in esophageal epithelia and adenocarcinoma cells. Improving our understanding of the cellular mechanisms that regulate Fas trafficking and turnover, cell-type specific differences in this regulation, and alterations that occur in malignancy could lead to effective, novel therapies for gastrointestinal malignancies and possibly many other diseases. This improved understanding may also alter the current management of gastroesophageal reflux disease, BE, and EA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--HUMAN STUDIES Principal Investigator & Institution: Jensen, Dennis M.; Professor of Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: (Adapted from the application) The mission of the Human Studies Core is to provide shared resources, personnel, services, education, and consultation to CURE investigators, trainees, and their collaborators for the study of patients with selected digestive diseases. The primary goal of this core is to facilitate collaboration, education about, and performance of GI clinical trials, human physiological studies, and health service studies in digestive diseases. The traditional focus of the core has been the investigation of peptic diseases and upper GI physiology, including secretion, motility, and hormonal regulation. This focus has been broadened to include the study of other important gastrointestinal illnesses such as complicated ulcer disease, gastroesophageal reflux disease (GERD), Barrett's epithelium, GI hemorrhage, non-ulcer dyspepsia,

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Helicobacter pylori infection, pre-cancer conditions (gastritis, polyposis, and ulcerative colitis), and inflammatory bowel disease. An overriding theme of the core is the study of the physiology of visceral pain which may be associated with all of these disorders. The importance of this area in GI diseases is highlighted by the impact of GI symptoms on quality of life and demand for health care services. With this in mind, the core has greatly expanded the study of neuroenteric diseases such as irritable bowel syndrome (IBS), non-ulcer dyspepsia, and non-cardiac chest pain. The specific goals of this core are to provide CURE investigators, trainees, and their collaborators with access to: (1) a quality clinical research unit for performance of GI clinical research at a low cost, (2) utilization of fully equipped endoscopy units for GI clinical and physiologic research studies, (3) laboratory services for GI secretory tests, GI motility and pH testing, and H. pylori assessments (ELISA, C-14 breath testing, and histopathology), (4) teaching of clinical research techniques and consultation about study design, data management, statistical analysis, and routine outcomes, (5) tissue and clinical data banks of patients with selected GI diseases (the largest data bases are for GI hemorrhage and functional GI disease), (6) consultation about conducting health services research including design of studies, cost assessments, quality of life instruments, effectiveness studies, and modeling cost-effectiveness studies, (7) specialized equipment for GI studies (such as equipment for ablating Barrett's epithelium or endoscopic ultrasound instruments), (8) psychophysiology and GI motility laboratories for the study of neuroenteric diseases, and (9) utilization of a brain imaging unit for the study of neuroenteric diseases. The instruments and personnel required for these services and functions are expensive, so that sharing them among various investigators in a core is cost effective and promotes collaboration. 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

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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 •

Project Title: EPIDEMIOLOGY AND INCIDENCE OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Corley, Douglas A.; Investigator; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Although the incidence of esophageal adenocarcinoma is rising more rapidly than that of any other malignancy, little is known about its pathogenesis. In particular, little population-based information is known about its main precursor lesion, Barrett's esophagus. The presence of Barrett's esophagus, a metaplastic esophageal columnar epithelium, effectively identifies persons at risk for esophageal adenocarcinoma. Thus, there is a compelling rationale for characterizing the incidence and major modifiable risk factors for Barrett's esophagus, and how these relate to purported risk factors for esophageal adenocarcinoma. Specific Aims/Methods: A. Evaluate the association between obesity/body fat distribution and Barrett's esophagus using a nested case-control study in the Northern California Kaiser Permanente (NCKP) population. The NCKP population contains approximately 3 million people, and is representative of the gender and ethnic distribution of Northern California. The study would use 313 cases, 313 population-based controls, and 313 controls with gastroesophageal reflux disease (who do not have Barrett's esophagus). We would employ a supplementary dietary questionnaire to evaluate for potential dietary confounders of the obesity-Barrett's esophagus relationship. B. Evaluate the association between serum antibody status for Helicobacter Pylori (including the virulent cagA+ strain) and Barrett's esophagus using a case-control study. C. Assay Barrett's esophagus patients and controls for iron stores and heterozygosity for the C282Y hemochromatosis gene mutation. D. Use the patients identified in these casecontrol studies to estimate the annual population-based incidence of Barrett's esophagus diagnosis. Obesity and body fat distribution, H.pylori infection, and iron stores represent potentially major, modifiable risk factors for Barrett's esophagus and esophageal adenocarcinoma. Our proposed study will: substantially extend current knowledge regarding the epidemiology of Barrett's esophagus; may partially explain why Barrett's esophagus/esophageal adenocarcinoma occurs predominantly in Caucasian males; estimate the population-based incidence of Barrett's esophagus diagnosis in the United States; and provide information for future intervention trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESOPHAGEAL MOTOR FUNCTION IN HEALTH AND DISEASE 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-JUL-1979; Project End 30-NOV-2004 Summary: (Adapted from the Applicant's Abstract): The overall objective of this grant is an in-depth investigation of pharyngoesophageal and laryngeal function in health and disease as it relates to gastroesophageal-pharyngeal reflux and aspiration. Gastroesophageal reflux disease is the most common malady of the esophagus. It is estimated that 7-10 percent of the US population suffers from various degrees of this disease. This translates into a significant burden on health care resources. However, complications of reflux disease induced outside the esophagus; namely in the aerodigestive and airway tracts, are now becoming increasingly recognized. For example, it is estimated that 410 percent of laryngeal diseases seen in ENT clinics are associated with reflux disease. However, progress in this field has lagged behind investigations in reflux related esophageal disorders. A substantial gap exists in our knowledge in regard to mechanisms of protection of supraesophageal regions from contact of gastric acid and pathophysiological basis of reflux related lesions in this region. Our specific objectives are: 1) to determine the pathophysiological basis of supraesophageal complications of gastroesophageal reflux disease. This section will include: characterization of regional pharyngeal distribution of gastric refluxate; characterization of the airway defensive reflexes against aspiration of gastroesophagopharyngeal reflux in the sleep state; determination of the effect of alcohol abuse on airway protective reflexes; and UES resistive function against esophagopharyngeal transit; physiology and pathophysiology of UES reflex response to gastroesophageal reflux, and 2) to investigate the sensory physiology of airway protective mechanisms. This section will include: characterization of the pharyngeal sensory field in relation to aerodigestive reflexes; functional localization of brain stem nuclei controlling esophageal and pharyngeal airway protective reflexes; and determination of the cerebral cortical representation of esophageal and pharyngeal viscerosensation as well as neuro-anatomical validation of FMRI cerebral response to esophageal stimulation. Individual, but interrelated protocols are proposed to achieve our objectives and will be executed by our multidisciplinary, interdepartmental team. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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Gastroesophageal Reflux Disease

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 •

Project Title: EZRIN IN STIMULUS-COUPLED GASTRIC ACID SECRETION Principal Investigator & Institution: Yao, Xuebiao; Molecular and Cell Biology; University of California Berkeley Berkeley, Ca 947205940 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-DEC-2002 Summary: Digestive function in the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of a cAMP-dependent protein kinase (PKA) cascade, which ultimately results in the insertion of gastric H,KATPases into the apical plasma membranes of parietal cells. This relocation of the H,KATPase occurs concomitantly with extensive remodeling of the actin cytoskeleton, which is also an essential step in the activation of acid secretion. While these aspects of parietal cell activation are well defined, the molecular mechanisms that couple PKAmediated phosphorylation to mobilization of H,K-ATPases and cytoskeletal remodeling are not known. A candidate coupling protein, ezrin, was identified as an 80 kDa phosphoprotein in parietal cells whose phosphorylation by PKA was related to parietal cell activation. Binding of ezrin to actin filaments is essential for gastric acid secretion. However, little is known regarding the molecular mechanism(s) by which ezrin operates in gastric acid secretion. The long-term goal of our research is to delineate the role of ezrin in stimulus-coupled epithelial secretion. To address this question, three Specific Aims ale proposed: first, we will identify the regions of ezrin necessary for beta-actin association using epitope-tagging, chemical footprinting, and crosslinking approaches. These studies will involve a detailed analysis of the structural determinants that mediate a direct ezrin-actin contact. Binding domain data will be used to design peptides that potently and specifically perturb ezrin-actin interactions in in vitro binding assays. The function of this interaction will then be determined by the effects of the peptides on acid secretion using permeabilized gastric glands. Second, we plan to determine the role of protein phosphorylation in the regulation of ezrin function by first mapping PKAmediated phosphorylation sites. The function of ezrin phosphorylation in acid secretion will then be defined by expressing non-phosphorylatable ezrin mutants in cultured parietal cells. Third, we will continue to identify and characterize novel ezrin-interacting proteins. These studies will be facilitated by using our newly generated monoclonal antibodies directed against a novel set of ezrin-binding proteins. Studying the molecular and cellular mechanisms underlying parietal cell activation is of general importance in understanding cellular physiology of regulated epithelial secretion in gut, and is also expected to be of great benefit in leading to pharmacological strategies for correcting

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abnormal gastric acid secretion in disorders such as gastric and duodenal ulcers, and gastroesophageal reflux disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FAMILIAL AGGREGATION OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Chak, Amitabh; Associate Professor; University Hospitals of Cleveland Lksd 1400 Cleveland, Oh 441065000 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: (provided by applicant): Esophageal adenocarcinoma is associated with a very poor prognosis. More effective screening, surveillance, and treatment strategies are required. The overall aim of this pilot proposal is to develop methodologies that will facilitate future multicenter studies aimed at assessing the familial aggregation of Barrett's esophagus and esophageal adenocarcinoma. Three specific methodologies will be developed: 1. A multicenter network will be established at five different institutions to enable the measurement of the prevalence of familial Barrett's esophagus. Familial Barrett's esophagus will be identified by administration of a questionnaire that has already been tested at University Hospitals of Cleveland. 2. Methodology will be developed to screen symptomatic first degree relatives of index patients with Barrett's esophagus and esophageal adenocarcinoma. Relatives with gastroesophageal reflux disease who have already been identified at University Hospitals of Cleveland through the study questionnaire will be recruited for screening endoscopy via mailings and phone calls. 3.Methodology will also be developed to recruit and screen asymptomatic or mildly symptomatic first degree using a new battery powered ultrathin endoscope. Successful conduct of this research proposal will result in the creation of a multi-center network, the identification of families with aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the development of methodology for detecting Barrett's esophagus in previously undiagnosed family members. These three achievements will permit future full-scale multi-center epidemiologic and genetic linkage studies with the ultimate goals of measuring the familial risk of Barrett's esophagus and the identification of susceptibility gene(s) that predispose individuals to the development of Barrett's esophagus. The results of these future investigations will aid the development of lower cost, more effective screening and surveillance programs for Barrett's esophagus. They will also define a population at risk in whom interventions to prevent or eradicate Barrett's esophagus can be applied. 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, which showed aggregation of reflux symptoms in families of probands with Barrett's

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Gastroesophageal Reflux Disease

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: H.PYLORI, GENES AND ESOPHAGEAL ADENOCARCINOMA Principal Investigator & Institution: Liu, Geoffrey; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Esophageal adenocarcinoma (EA) has the fastest rising incidence of all cancers in the United States. The overall annual incidence has more than tripled over a twenty year period. These statistics imply an urgent problem that needs addressing, and an environmental component to the etiology and pathogenesis of EA. Although gastroesophageal reflux disease, Barrett's esophagus and obesity are known risk factors for EA, more recently, a protective effect for Helicobacter pylori (HP) has been hypothesized based on the results of several studies. One objective of this research is to confirm earlier results in a large sample of over 250 histologically-confirmed incident EA cases. Through a secondary analysis of data and specimens from two separate molecular epidemiologic studies, the association between Helicobacter pylori and EA risk will be examined via a case-control design, after taking into account important covariates such as gastroesophageal reflux, Barrett's esophagus, and body-mass index. In addition, there may be host factors such as genetic polymorphisms that modify the relationship between HP and EA risk. Genetic polymorphisms involved in three pathways will be evaluated as potential modifiers of this relationship: (a) genes in the inflammatory pathway, such as IL1-beta; (b) genes involved in free radical formation such as MPO and MnSOD; and (c) several candidate DNA repair genes. Both single nucleotide polymorphisms and haplotypes will be evaluated as potential modifiers of the HP-EA risk association. One long-term goal of this small grant project is to generate information that will ultimately lead to a more comprehensive large scale population-based case-control study of EA risks. This application addresses directly priorities set by the NCl, in particular, the recommendations of the Stomach and Esophageal Cancer Progress Report Group (2002), and may have important impact on current medical practices related to the aggressiveness of treating HP infections. 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

33

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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Gastroesophageal Reflux Disease

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: 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 "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

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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

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(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 •

Project Title: OPTICAL DETECTION OF BARRETT'S UNDER SQUAMOUS EPITHELIUM Principal Investigator & Institution: Kimmey, Michael B.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): This proposal is a collaborative, multi-disciplinary program involving researchers in the Departments of Medicine, Pathology, and Bioengineering at the University of Washington. Our objective is to investigate the feasibility of detecting Barrett's epithelium underneath squamous epithelium using optical coherence tomography (OCT). Barrett's esophagus is a premalignant condition found in 5% to 10% of patients with gastroesophageal reflux disease. Barrett's patients have a 30- to 50-fold increased risk of developing esophageal adenocarcinoma. Recently, a number of endoscopic treatments have been developed to ablate Barrett's epithelium. However, approximately 5% to 10% of patients have areas of residual Barrett's epithelium underneath the newly replaced squamous epithelium. This is a problematic condition since the underlying Barrett's is no longer visible to the endoscopist and the patient is still at risk for esophageal cancer. OCT is an emerging non-invasive diagnostic technique capable of cross-sectional imaging of tissue microstructure in real time. OCT imaging depth is 1-3 mm in most highly scattering tissues and imaging can be performed at 1-2 pm resolution. The hypothesis of this proposal is that OCT can detect Barrett's epithelium underlying the esophageal squamous epithelium during endoscopy. The specific aims of this proposal are to develop an OCT system along with a compact X-Y scanning probe that can perform real time imaging at 1.5 pm resolution. The OCT probe will be used to image ex vivo esophagectomy specimens from Barrett's patients to determine if it is feasible to detect Barrett's epithelium underneath squamous epithelium. In addition, an OCT balloon catheter will be developed that permits stabilization and systematic imaging of the esophagus over a large area. The OCT balloon catheter will be characterized on ex vivo resected swine esophagi and finally will be perfected for use during in vivo endoscopy in anesthetized swine. Imaged tissues will be processed for histology to compare with the OCT images. If successful, this technology could also be used to detect premalignant conditions (such as dysplasia) and early cancer. It is anticipated that a larger, longer term grant will be required for further refinements of the technology and for determining the prevalence of residual Barrett's under squamous epithelium following various types of endoscopic ablation procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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: PRESYNAPTIC MECHANISMS IN THE INTESTINE Principal Investigator & Institution: Galligan, James J.; Professor; Pharmacology and Toxicology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 30-JUN-2004 Summary: Presynaptic mechanisms are an important means for neurotransmitters, hormones, paracrine substances and drugs to modulate the activity of myenteric nerves and gut motility. Despite the clear importance of presynaptic mechanisms in regulating neurotransmission in the myenteric plexus, little is known about the details of these mechanisms. The proposed studies are designed to characterize these mechanisms. Electrophysiological methods will be used to study excitatory synaptic transmission between myenteric neurons in acutely isolated preparations of guinea pig intestine and between guinea pig myenteric neurons maintained under tissue culture conditions. These studies will investigate the contributions of acetylcholine (ACh) acting at nicotinic cholinergic receptors and ATP acting at P2X purine receptors, to fast excitatory synaptic potentials (fEPSPs) during long trains of stimulation. As nicotinic receptors desensitize quickly, it is anticipated that ACh will be the predominate transmitter early while ATP will predominate later in the train of activity. Presynaptic mechanisms controlling the release of these two important transmitters will also be investigated. These studies will focus on channels which provide the calcium needed for transmitter release and the presynaptic receptors which facilitate their release. The facilitatory effects of 5-HT4 receptor activation on fEPSPs mediated by ACh and ATP will be investigated. In addition, these studies will investigate the contribution of 5-HT3 and 5-HT4 receptors to excitation of enteric sensory nerve terminals. The role of presynaptic nicotinic acetylcholine receptors (nAChRs) in controlling the release of the slow synaptic transmitters, substance P/neurokinin A will also be investigated. These latter studies will attempt to establish that there are presynaptic nAChRs on the terminals of sensory neurons and that ACh released from sensory neurons facilitates SP/NKA release and enhances slow excitatory synaptic transmission. There are many disorders of gut motility which have their basis either directly or indirectly in alterations in enteric neurotransmission. These disorders include gastroesophageal reflux disease, the irritable bowel syndrome and chronic intestinal pseudo-obstruction. It is anticipated that these studies will provide new insights into mechanisms of synaptic transmission in the gut which could lead to the development of new and effect drug treatments for motility disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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: REGULATION OF CALCIUM RELEASE IN INTESTINAL MYOCYTES Principal Investigator & Institution: Bielefeldt, Klaus; Associate Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 24-AUG-1998; Project End 31-MAY-2004 Summary: The normal gastrointestinal motility depends on a cascade of intracellular signals that translate a signal at the cell membrane into muscle contraction. The calcium ion plays a central role in this process of excitation-contraction coupling. Changes in the calcium homeostasis of smooth muscle cells may thus contribute to common gastrointestinal diseases, such as constipation, diarrhea, or gastroesophageal reflux disease. Increases in the cytosolic calcium level can be due to calcium influx through ion channels in the cell membrane or calcium release from intracellular stores. Two intracellular calcium release channels have been identified in intestinal smooth muscle cells: the inositol 1,4,5-trisphosphate receptor channel and the ryanodine receptor

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channel. Little is known about the mechanisms that modulate the activity of these intracellular calcium release channels. We hypothesize that ryanodine receptor channel isoforms are differentially expressed in gastro-intestinal smooth muscle from anatomically and functionally distinct areas; associated modulatory proteins further increase this heterogeneity, thereby affecting intestinal motor function. The proposed experiments will investigate the regulation of calcium release from intracellular stores. The following specific goals will be addressed: (1) Biochemical and functional characterization of calcium release channels expressed in intestinal smooth muscle cells. (2) Identification of proteins associated with ryanodine receptor channels in intestinal smooth muscle cells. (3) Characterization of the functional role of proteins associated with the ryanodine receptor channel. A better understanding of mechanisms that control the calcium homeostasis may provide important insight into the etiology of diseases or lead to the development of novel treatment strategies for functional abnormalities. 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, 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

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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: STUDIES IN CHILDREN WITH DIGESTIVE DISORDERS Principal Investigator & Institution: Heyman, Melvin B.; Professor of Pediatrics; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: Clinical research in pediatric disorders is essential to ensure advances in the management, prognosis and quality of life of infants, children and adolescents with these problems. The goals are (1) to foster a program in hypothesis-driven, expert clinical research in pediatric gastroenterology and nutrition, (2) to mentor young clinicians in pediatric gastroenterology and nutrition research, and (3) to promote ongoing interactions and collaborations with clinical investigators. To achieve these goals, current projects and future investigations of gastrointestinal and nutrition

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problems in pediatric patients will be conducted by trainees at various levels under the guidance and supervision of Dr. Heyman and his collaborators. Studies involving pediatric patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), HIV infection, familial adenomatous polyposis syndrome (with FAP gene mutations), ichthyosis erythrodermas with poor nutrition, and gastroesophageal reflux disease are currently ongoing or planned utilizing the facilities and staffs of the Pediatric Gastroenterology/Nutrition Clinics and the Pediatric Clinical Research Center at the University of California, San Francisco (UCSF). A cohort study is in the planning stage to determine whether nutrition advice promotes improved long-term outcomes in eating behaviors and health status (e.g., micronutrient adequacy; and growth parameters). The overriding objective of this proposal is to motivate and inspire young clinicians embarking on careers focused on clinically oriented research. Pediatric gastroenterology trainees will be instructed in the proper conduct of perspective randomized controlled clinical trials in infants, children, and adolescents. Trainees will also participate in didactic courses covering clinical trial design and procedure, protocol writing, data management, and ethical considerations. This award will enhance the applicant's ability to devote more time to research- related activities, and to provide guidance and instruction for trainees advancing towards productive scientific careers. 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 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

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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 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: TRANSGENIC MOUSE MODEL FOR BARRETT'S ESOPHAGUS Principal Investigator & Institution: Cotsarelis, George; Assistant Professor; Dermatology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The incidence of adenocarcinoma of the esophagus in the United States is increasing at an alarming rate. 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 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 injury model for Barrett's esophagus in transgenic mice so that we may 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 gone using this promoter, we discovered that intestinal metaplasia that closely mimics Barrett's esophagus develops at the squamocolumnar junction after administration of ganciclovir. In this proposal, we plan to 1. optimize the conditions for developing intestinal metaplasia, and test the reversibility of the metaplasia; 2. validate this transgenic mouse model for Barrett's

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esophagus at the molecular level; 3. assess the role of p53 mutations on development of intestinal metaplasia, dysplasia and adenocarcinoma at the squamocolumnar junction in the stomach; 4. study changes in gene expression during the metaplastic transformation. This would be the first transgenic inducible injury model that mimics Barrett's esophagus. It should be a valuable resource for those interested in studying the pathogenesis, chemoprevention and treatment of Barrett's esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “gastroesophageal reflux disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for gastroesophageal reflux disease in the PubMed Central database: •

Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project. by Harvey RF, Lane JA, Murray LJ, Harvey IM, Donovan JL, Nair P.; 2004 Jun 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=421785

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Whither surgery in the treatment of gastroesophageal reflux disease (GERD)? by Urbach DR, Ungar WJ, Rabeneck L.; 2004 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=315527

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals.

3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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

A 59-year-old woman with gastroesophageal reflux disease and Barrett esophagus. Author(s): Spechler SJ. Source: Jama : the Journal of the American Medical Association. 2003 January 22-29; 289(4): 466-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533126

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A comparison of laparoscopic Toupet versus Nissen fundoplication in gastroesophageal reflux disease. Author(s): Zugel N, Jung C, Bruer C, Sommer P, Breitschaft K. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2002 January; 386(7): 494-8. Epub 2001 November 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11819105

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A critical review of endoscopic therapy for gastroesophageal reflux disease. Author(s): Hogan WJ, Shaker R. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 201S-210S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928102

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A pharmacoeconomic comparison of the efficacy and costs of pantoprazole and omeprazole for the treatment of peptic ulcer or gastroesophageal reflux disease in The Netherlands. Author(s): van Hout BA, Klok RM, Brouwers JR, Postma MJ. Source: Clinical Therapeutics. 2003 February; 25(2): 635-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749518

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A review of the atypical manifestations of gastroesophageal reflux disease. Author(s): Chandra A, Moazzez R, Bartlett D, Anggiansah A, Owen WJ. Source: Int J Clin Pract. 2004 January; 58(1): 41-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14994970

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Absence of gastroesophageal reflux disease in a majority of patients taking acid suppression medications after Nissen fundoplication. Author(s): Lord RV, Kaminski A, Oberg S, Bowrey DJ, Hagen JA, DeMeester SR, Sillin LF, Peters JH, Crookes PF, DeMeester TR. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 January-February; 6(1): 3-9; Discussion 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986011

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Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings. Author(s): Sifrim D, Holloway R, Silny J, Xin Z, Tack J, Lerut A, Janssens J. Source: Gastroenterology. 2001 June; 120(7): 1588-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11375941

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An association between central serous chorioretinopathy and gastroesophageal reflux disease. Author(s): Mansuetta CC, Mason JO 3rd, Swanner J, Feist RM, White MF Jr, Thomley ML, McGwin G Jr, Emond TL. Source: American Journal of Ophthalmology. 2004 June; 137(6): 1096-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15183795

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An early cancer of the gastric cardia arising from carditis after long-term gastroesophageal reflux disease in the absence of Helicobacter pylori infection. Author(s): Yagi K, Nakamura A, Sekine A, Oyamatsu M, Tamiya Y, Watanabe H. Source: Journal of Gastroenterology and Hepatology. 2002 November; 17(11): 1236-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453287

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And then there were three--endotherapy for gastroesophageal reflux disease. Author(s): DiBaise JK. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1909-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499763

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Anterior partial fundoplication for gastroesophageal reflux disease. Author(s): Kneist W, Heintz A, Trinh TT, Junginger T. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2003 July; 388(3): 174-80. Epub 2003 July 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845536

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Approach and management of patients with recurrent gastroesophageal reflux disease. Author(s): Hunter JG. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2001 September-October; 5(5): 451-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11985994

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Asia-Pacific consensus on gastroesophageal reflux disease. Author(s): Wong WM, Hui WM, Wong BC. Source: Journal of Gastroenterology and Hepatology. 2004 April; 19(4): 353-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15012770

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Assessing NSAID prescription use as a predisposing factor for gastroesophageal reflux disease in a Medicaid population. Author(s): Kotzan J, Wade W, Yu HH. Source: Pharmaceutical Research. 2001 September; 18(9): 1367-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11683254

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Association between Zenker diverticulum and gastroesophageal reflux disease: development of a working hypothesis. Author(s): Sasaki CT, Ross DA, Hundal J. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 169S-171S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928096

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Association of asthma with gastroesophageal reflux disease in children. Author(s): Ay M, Sivasli E, Bayraktaroglu Z, Ceylan H, Coskun Y. Source: J Chin Med Assoc. 2004 February; 67(2): 63-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15146900

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Association of gastroesophageal reflux disease in young children with persistent respiratory symptoms. Author(s): Jain A, Patwari AK, Bajaj P, Kashyap R, Anand VK. Source: Journal of Tropical Pediatrics. 2002 February; 48(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866335

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Association of gastroesophageal reflux disease with weight gain and apnea, and their disturbance on sleep. Author(s): Suganuma N, Shigedo Y, Adachi H, Watanabe T, Kumano-Go T, Terashima K, Mikami A, Sugita Y, Takeda M. Source: Psychiatry and Clinical Neurosciences. 2001 June; 55(3): 255-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422864

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Association of laryngopharyngeal symptoms with gastroesophageal reflux disease. Author(s): Tauber S, Gross M, Issing WJ. Source: The Laryngoscope. 2002 May; 112(5): 879-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12150622

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Autosomal dominant infantile gastroesophageal reflux disease: exclusion of a 13q14 locus in five well characterized families. Author(s): Orenstein SR, Shalaby TM, Finch R, Pfuetzer RH, DeVandry S, Chensny LJ, Bannada MM, Whitcomb DC. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2725-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425539

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Barrett's esophagus in patients with gastroesophageal reflux disease. Medical therapy or antireflux surgery? Author(s): Klaus A, Muhlmann G, Kirchmayr W, Weiss H, Wetscher GJ. Source: Minerva Chir. 2002 August; 57(4): 397-402. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145570

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Barrett's esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Author(s): Winters C Jr, Spurling TJ, Chobanian SJ, Curtis DJ, Esposito RL, Hacker JF 3rd, Johnson DA, Cruess DF, Cotelingam JD, Gurney MS, et al. Source: Gastroenterology. 1987 January; 92(1): 118-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3781178

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Basal acid output and gastric acid hypersecretion in gastroesophageal reflux disease. Correlation with ranitidine therapy. Author(s): Collen MJ, Johnson DA, Sheridan MJ. Source: Digestive Diseases and Sciences. 1994 February; 39(2): 410-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8313826

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Basal acid output in gastroesophageal reflux disease. Author(s): Collen MJ, Johnson DA, Sheridan MJ. Source: Gastroenterology. 1992 June; 102(6): 2182-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1587449

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Basic considerations in gastroesophageal reflux disease. Author(s): Donahue PE. Source: The Surgical Clinics of North America. 1997 October; 77(5): 1017-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9347829

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Belching: dyspepsia or gastroesophageal reflux disease? Author(s): Lin M, Triadafilopoulos G. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2139-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572558

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Belsey Mark IV antireflux procedure for complicated gastroesophageal reflux disease. Author(s): Fenton KN, Miller JI Jr, Lee RB, Mansour KA. Source: The Annals of Thoracic Surgery. 1997 September; 64(3): 790-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9307475

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Beyond heartburn: extraesophageal manifestations of gastroesophageal reflux disease. Author(s): Richter JE. Source: Am J Manag Care. 2001 February; 7(1 Suppl): S6-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225351

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Biology of gastroesophageal reflux disease: pathophysiology relating to medical and surgical treatment. Author(s): DeMeester TR, Peters JH, Bremner CG, Chandrasoma P. Source: Annual Review of Medicine. 1999; 50: 469-506. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10073290

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Brazilian consensus on gastroesophageal reflux disease: proposals for assessment, classification, and management. Author(s): Moraes-Filho J, Cecconello I, Gama-Rodrigues J, Castro L, Henry MA, Meneghelli UG, Quigley E; Brazilian Consensus Group. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 241-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866257

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Breath alcohol analysis in one subject with gastroesophageal reflux disease. Author(s): Gullberg RG. Source: J Forensic Sci. 2001 November; 46(6): 1498-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11714167

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Breath tests for alcohol in gastroesophageal reflux disease. Author(s): Kechagias S, Jonsson KA, Jones AW. Source: Annals of Internal Medicine. 1999 February 16; 130(4 Pt 1): 328-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10068396

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Care modes for the older adult with gastroesophageal reflux disease. Author(s): Dunmore F. Source: Geriatric Nursing (New York, N.Y.). 2002 July-August; 23(4): 212-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12183747

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Case-control comparison of endoscopic gastroplication with laparoscopic fundoplication in the management of gastroesophageal reflux disease: early symptomatic outcomes. Author(s): Velanovich V, Ben-Menachem T, Goel S. Source: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. 2002 August; 12(4): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12193813

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Chronic cough and gastroesophageal reflux disease: experience with specific therapy for diagnosis and treatment. Author(s): Poe RH, Kallay MC. Source: Chest. 2003 March; 123(3): 679-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12628862

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Chronic cough due to gastroesophageal reflux disease: efficacy of antireflux surgery. Author(s): Novitsky YW, Zawacki JK, Irwin RS, French CT, Hussey VM, Callery MP. Source: Surgical Endoscopy. 2002 April; 16(4): 567-71. Epub 2002 January 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972189

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Chronic cough due to gastroesophageal reflux disease: failure to resolve despite total/near-total elimination of esophageal acid. Author(s): Irwin RS, Zawacki JK, Wilson MM, French CT, Callery MP. Source: Chest. 2002 April; 121(4): 1132-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948043

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Chronic cough, sleep apnea, and gastroesophageal reflux disease. Author(s): Herr J. Source: Chest. 2001 September; 120(3): 1036-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555550

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Chronic gastroesophageal reflux disease and its effect on laryngeal visualization and intubation: a case report. Author(s): Stevens L. Source: Aana Journal. 2002 October; 70(5): 373-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425126

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Chronic inactive gastritis and coccoid Helicobacter pylori in patients treated for gastroesophageal reflux disease or with H pylori eradication therapy. Author(s): Goldstein NS. Source: American Journal of Clinical Pathology. 2002 November; 118(5): 719-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428792

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Chronic middle ear disease and gastroesophageal reflux disease: a causal relation? Author(s): Poelmans J, Tack J, Feenstra L. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2001 July; 22(4): 447-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11449097

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Clinical and demographic predictors of Barrett's esophagus among patients with gastroesophageal reflux disease: a multivariable analysis in veterans. Author(s): Eloubeidi MA, Provenzale D. Source: Journal of Clinical Gastroenterology. 2001 October; 33(4): 306-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588545

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Clinical features and endoscopic progression of gastroesophageal reflux disease. Author(s): Garrido Serrano A, Guerrero Igea FJ, Lepe Jimenez JA, Perianes Hernandez C. Source: Rev Esp Enferm Dig. 2003 October; 95(10): 712-6, 707-11. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14588065

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Clinical implications of gastroesophageal reflux disease and swallowing dysfunction in COPD. Author(s): Mokhlesi B. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2003; 2(2): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720011

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Combination drug therapy for gastroesophageal reflux disease. Author(s): Cross LB, Justice LN. Source: The Annals of Pharmacotherapy. 2002 May; 36(5): 912-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978171

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Community issues in gastroesophageal reflux disease: what we know and what we do not know. Author(s): Bjorkman DJ. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S34-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510768

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Comparison between pediatricians and family practitioners in the use of the prokinetic cisapride for gastroesophageal reflux disease in children. Author(s): Shaoul R, Shahory R, Tamir A, Jaffe M. Source: Pediatrics. 2002 June; 109(6): 1118-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042552

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Comparison of open and laparoscopic antireflux surgery for the treatment of gastroesophageal reflux disease in Taiwanese. Author(s): Lai IR, Lee YC, Lee WJ, Yuan RH. Source: J Formos Med Assoc. 2002 August; 101(8): 547-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12440084

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Comparison of pantoprazole 20 mg to ranitidine 150 mg b.i.d. in the treatment of mild gastroesophageal reflux disease. Author(s): Kaspari S, Biedermann A, Mey J. Source: Digestion. 2001; 63(3): 163-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11351143

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Compliance measurement of lower esophageal sphincter and esophageal body in achalasia and gastroesophageal reflux disease. Author(s): Jenkinson AD, Scott SM, Yazaki E, Fusai G, Walker SM, Kadirkamanathan SS, Evans DF. Source: Digestive Diseases and Sciences. 2001 September; 46(9): 1937-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575446

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Correlation between intestinal metaplasia of the gastric cardia and gastroesophageal reflux disease. Author(s): Lanzafame S, Torrisi A, Favara C, Russo V, Emmanuele C. Source: Hepatogastroenterology. 2001 July-August; 48(40): 1007-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490786

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Critical review of the epidemiology of gastroesophageal reflux disease with specific comparisons to asthma and breast cancer. Author(s): Johanson JF. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S19-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510764

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Decision making in gastroesophageal reflux disease. What are the critical issues? Author(s): Ofman JJ. Source: Gastroenterology Clinics of North America. 2002 December; 31(4 Suppl): S67-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489472

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Decreased sympathetic inhibition in gastroesophageal reflux disease. Author(s): Campo SM, Capria A, Antonucci F, Martino G, Ciamei A, Rossini PM, Bologna E, Cannata D. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2001 February; 11(1): 45-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11503951

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Definition of histopathologic changes in gastroesophageal reflux disease. Author(s): Chandrasoma PT, Lokuhetty DM, Demeester TR, Bremmer CG, Peters JH, Oberg S, Groshen S. Source: The American Journal of Surgical Pathology. 2000 March; 24(3): 344-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10716147

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Delayed gastric emptying in gastroesophageal reflux disease: reassessment with new methods and symptomatic correlations. Author(s): Buckles DC, Sarosiek I, McMillin C, McCallum RW. Source: The American Journal of the Medical Sciences. 2004 January; 327(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722388

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Dental erosion caused by silent gastroesophageal reflux disease. Author(s): Ali DA, Brown RS, Rodriguez LO, Moody EL, Nasr MF. Source: The Journal of the American Dental Association. 2002 June; 133(6): 734-7; Quiz 768-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083649

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Dental erosion in gastroesophageal reflux disease. Author(s): Barron RP, Carmichael RP, Marcon MA, Sandor GK. Source: Journal (Canadian Dental Association). 2003 February; 69(2): 84-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559056

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Detection of Helicobacter pylori with stool antigen test in children with gastroesophageal reflux disease. Author(s): Demir H, Ercis S, Kocak N, Hascelik G, Ozen H, Yuce A, Gurakan F, Saltik IN. Source: The American Journal of Gastroenterology. 2001 June; 96(6): 1944. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11419862

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Determining an appropriate threshold for referral to surgery for gastroesophageal reflux disease. Author(s): Liu JY, Finlayson SR, Laycock WS, Rothstein RI, Trus TL, Pohl H, Birkmeyer JD. Source: Surgery. 2003 January; 133(1): 5-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12563232

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Diagnosing gastroesophageal reflux disease. Author(s): Szarka LA, DeVault KR, Murray JA. Source: Mayo Clinic Proceedings. 2001 January; 76(1): 97-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11155424

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Diagnosis and management of gastroesophageal reflux disease in the primary care setting: can health-related quality of life play a role? Author(s): Gralnek IM. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S54-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510772

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Diagnosis and treatment of gastroesophageal reflux disease in infants and children. Author(s): Vandenplas Y. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 November; 14 Suppl D: 26D-34D. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110609

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Diagnosis and treatment of gastroesophageal reflux disease in Ohio Medicaid patients: practice patterns and temporal trends. Author(s): Cooper GS, Mourad WA, Koroukian SM. Source: Pharmacoepidemiology and Drug Safety. 2004 January; 13(1): 21-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14971119

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Diagnosis of gastroesophageal reflux disease in elderly subjects using 24-hour esophageal pH monitoring. Author(s): Wu B, Wang M, Li Y. Source: Chinese Medical Journal. 1999 April; 112(4): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593533

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Diagnosis of gastroesophageal reflux disease in general practice: a Belgian national survey. Author(s): Eisendrath P, Tack J, Deviere J. Source: Endoscopy. 2002 December; 34(12): 998-1003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12471545

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Diagnosis of symptomatic gastroesophageal reflux disease. Author(s): Kahrilas PJ. Source: The American Journal of Gastroenterology. 2003 March; 98(3 Suppl): S15-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644027

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Diagnostic evaluation in gastroesophageal reflux disease. Author(s): Younes Z, Johnson DA. Source: Gastroenterology Clinics of North America. 1999 December; 28(4): 809-30, V. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695003

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Diagnostic tests for gastroesophageal reflux disease. Author(s): Richter JE. Source: The American Journal of the Medical Sciences. 2003 November; 326(5): 300-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615671

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Disease-specific outcomes assessment for gastroesophageal reflux disease. Author(s): Lieberman D. Source: Gastrointest Endosc Clin N Am. 1999 October; 9(4): 657-63, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10495230

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Does major depression in patients with gastroesophageal reflux disease affect the outcome of laparoscopic antireflux surgery? Author(s): Kamolz T, Granderath FA, Pointner R. Source: Surgical Endoscopy. 2003 January; 17(1): 55-60. Epub 2002 September 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239650

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Does the duration of gastroesophageal reflux disease and degree of acid reflux correlate with esophageal function? A retrospective analysis of 768 patients. Author(s): Shiino Y, Filipi CJ, Tomonaga T, Awad ZT, Marsh RE. Source: Journal of Clinical Gastroenterology. 2000 January; 30(1): 56-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636211

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Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Author(s): Furuta T, Shirai N, Watanabe F, Honda S, Takeuchi K, Iida T, Sato Y, Kajimura M, Futami H, Takayanagi S, Yamada M, Ohashi K, Ishizaki T, Hanai H. Source: Clinical Pharmacology and Therapeutics. 2002 October; 72(4): 453-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386647

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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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Efficacy of lansoprazole in the treatment of gastroesophageal reflux disease in children. Author(s): Tolia V, Ferry G, Gunasekaran T, Huang B, Keith R, Book L. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002; 35 Suppl 4: S308-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607791

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Endoluminal methods of treating gastroesophageal reflux disease. Author(s): Roy-Shapira A, Stein HJ, Scwartz D, Fich A, Sonnenschein E. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(2): 132-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220420

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Endoluminal therapies for gastroesophageal reflux disease. Author(s): Behm BW, Stollman N. Source: Journal of Clinical Gastroenterology. 2004 March; 38(3): 209-17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128065

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Endoscope-based treatments for gastroesophageal reflux disease. Author(s): Hailey D. Source: Issues Emerg Health Technol. 2004 March; (54): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027474

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Endoscopic implantation of enteryx for the treatment of gastroesophageal reflux disease: technique, pre-clinical and clinical experience. Author(s): Louis H, Deviere J. Source: Gastrointest Endosc Clin N Am. 2003 January; 13(1): 191-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797438

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Endoscopic suturing for gastroesophageal reflux disease: clinical outcome with the Bard EndoCinch. Author(s): Rothstein RI, Filipi CJ. Source: Gastrointest Endosc Clin N Am. 2003 January; 13(1): 89-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797429

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Endoscopic therapy for gastroesophageal reflux disease: what have we learned and what needs to be done? Author(s): Fennerty MB. Source: Gastrointest Endosc Clin N Am. 2003 January; 13(1): 201-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797439

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Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease. Author(s): Isomoto H, Saenko VA, Kanazawa Y, Nishi Y, Ohtsuru A, Inoue K, Akazawa Y, Takeshima F, Omagari K, Miyazaki M, Mizuta Y, Murata I, Yamashita S, Kohno S. Source: The American Journal of Gastroenterology. 2004 April; 99(4): 589-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15089887

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Epidemiology and costs of gastroesophageal reflux disease in Switzerland: a population-based study. Author(s): Schwenkglenks M, Marbet UA, Szucs TD. Source: Sozial- Und Praventivmedizin. 2004; 49(1): 51-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040129

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Epidemiology and pathophysiology of symptomatic gastroesophageal reflux disease. Author(s): Fass R. Source: The American Journal of Gastroenterology. 2003 March; 98(3 Suppl): S2-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644025

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Epidemiology of gastroesophageal reflux disease: a general population-based study in Xi'an of Northwest China. Author(s): Wang JH, Luo JY, Dong L, Gong J, Tong M. Source: World Journal of Gastroenterology : Wjg. 2004 June 1; 10(11): 1647-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15162542

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Esophageal complications of gastroesophageal reflux disease: presentation, diagnosis, management, and outcomes. Author(s): Spechler SJ. Source: Clinical Cornerstone. 2003; 5(4): 41-8; Discussion 49-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101494

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Esophageal function studies in the management of gastroesophageal reflux disease. Author(s): Incarbone R, Bonavina L, Reitano M, Peracchia A. Source: International Journal of Surgical Investigation. 1999; 1(4): 351-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774461

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Evaluation of gastroesophageal reflux disease following various reconstructive procedures for a distal gastrectomy. Author(s): Kawamura T, Yasui A, Shibata Y, Yuasa N, Nimura Y. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2003 September; 388(4): 250-4. Epub 2003 August 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12910420

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Evaluation of symptom index in identifying gastroesophageal reflux disease-related noncardiac chest pain. Author(s): Dekel R, Martinez-Hawthorne SD, Guillen RJ, Fass R. Source: Journal of Clinical Gastroenterology. 2004 January; 38(1): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679323

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Evidence-based practice: gastroesophageal reflux disease. Author(s): Saddler D. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2003 May-June; 26(3): 125-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811323

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Expectations of patients with gastroesophageal reflux disease for the outcome of laparoscopic antireflux surgery. Author(s): Kamolz T, Pointner R. Source: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. 2002 December; 12(6): 389-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12496543

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Extraesophageal manifestations of gastroesophageal reflux disease. Author(s): Vaezi MF. Source: Clinical Cornerstone. 2003; 5(4): 32-8; Discussion 39-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101493

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Factors affecting esophageal motility in gastroesophageal reflux disease. Author(s): Chrysos E, Prokopakis G, Athanasakis E, Pechlivanides G, Tsiaoussis J, Mantides A, Xynos E. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 March; 138(3): 241-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611566

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Factors that influence therapeutic outcomes in symptomatic gastroesophageal reflux disease. Author(s): Quigley EM. Source: The American Journal of Gastroenterology. 2003 March; 98(3 Suppl): S24-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644028

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Familial factors in the etiology of gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma. Author(s): Trudgill N. Source: Chest Surg Clin N Am. 2002 February; 12(1): 15-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11901927

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Famotidine in gastroesophageal reflux disease (GERD). Author(s): Wesdorp IC. Source: Hepatogastroenterology. 1992 February; 39 Suppl 1: 24-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1577391

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Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group. Author(s): Sabesin SM, Berlin RG, Humphries TJ, Bradstreet DC, Walton-Bowen KL, Zaidi S. Source: Archives of Internal Medicine. 1991 December; 151(12): 2394-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746996

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Fasting and postprandial mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease. Author(s): Cucchiara S, Bortolotti M, Minella R, Auricchio S. Source: Digestive Diseases and Sciences. 1993 January; 38(1): 86-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8420764

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Features of symptomatic gastroesophageal reflux disease in elderly patients. Author(s): Triadafilopoulos G, Sharma R. Source: The American Journal of Gastroenterology. 1997 November; 92(11): 2007-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9362181

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Felodipine does not increase the reflux episodes in patients with gastroesophageal reflux disease. Author(s): Wu JH, Chang CS, Chen GH, Poon SK, Ko CW. Source: Hepatogastroenterology. 2000 September-October; 47(35): 1328-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11100344

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Fundoplication controversies in the treatment of pediatric gastroesophageal reflux disease. Introduction. Author(s): Ashcraft KW. Source: Semin Pediatr Surg. 1998 May; 7(2): 108-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9597702

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Future opportunities and developments for endoscopic gastroesophageal reflux disease therapy. Author(s): Ramage JI Jr, Feitoza AB, Gostout CJ. Source: Gastrointest Endosc Clin N Am. 2003 January; 13(1): 211-21, Xii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797440

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Gastroesophageal reflux disease and Barrett's esophagus. Author(s): Koop H. Source: Endoscopy. 2004 February; 36(2): 103-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765307

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Gastroesophageal reflux disease and diarrhea. Author(s): Riegler M, Cosentini EP. Source: The American Journal of Medicine. 2004 May 15; 116(10): 717; Author Reply 7178. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15121500

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Gastroesophageal reflux disease and Helicobacter pylori infection in neurologically impaired children: inter-relations and therapeutic implications. Author(s): Pollet S, Gottrand F, Vincent P, Kalach N, Michaud L, Guimber D, Turck D. Source: Journal of Pediatric Gastroenterology and Nutrition. 2004 January; 38(1): 70-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676598

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Gastroesophageal reflux disease at the turn of millennium. Author(s): Lim LG, Ho KY. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2135-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562363

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Gastroesophageal reflux disease in children: need for long-term medical treatment. Author(s): Demir H, Nur I, Temizel S, Ozen H, Gurakan F, Yuce A, Kocak N. Source: Indian J Gastroenterol. 2003 September-October; 22(5): 197-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14658545

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

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Gastroesophageal reflux disease in the elderly. Author(s): Williams JL. Source: Director. 2003 Summer; 11(3): 107-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678021

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Gastroesophageal reflux disease is not a significant cause of lung disease in children. Author(s): Weinberger M. Source: Pediatr Pulmonol Suppl. 2004; 26: 197-200. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15029650

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Gastroesophageal reflux disease, tooth erosion, and prosthodontic rehabilitation: a clinical report. Author(s): Van Roekel NB. Source: Journal of Prosthodontics : Official Journal of the American College of Prosthodontists. 2003 December; 12(4): 255-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061234

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Gastroesophageal reflux disease: a dental concern. Author(s): Lackey MA, Barth J. Source: Gen Dent. 2003 May-June; 51(3): 250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15055710

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Gastroesophageal reflux disease: a historical review of surgical therapy. Author(s): Little AG. Source: The Journal of Surgical Research. 2004 March; 117(1): 30-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013711

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Gastroesophageal reflux disease: a typical spectrum disease (a new conceptual framework is not needed). Author(s): Pace F, Porro GB. Source: The American Journal of Gastroenterology. 2004 May; 99(5): 946-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128365

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Gastroesophageal reflux disease: clinical manifestations. Author(s): Williams JL. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2003 September-October; 26(5): 195-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603078

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Gastroesophageal reflux disease: current diagnosis and treatment. Author(s): Harris JP, Weiss CA 3rd, Schwartz RW. Source: Current Surgery. 2003 January-February; 60(1): 40-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14972310

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Gastroesophageal reflux disease: current treatment approaches. Author(s): Biddle W. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2003 November-December; 26(6): 228-36; Quiz 236-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676609

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Gastroesophageal reflux disease: current treatment approaches. Author(s): Biddle W. Source: Director. 2003 Fall; 11(4): 155-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608699

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Gastroesophageal reflux disease: natural history and long-term medical and surgical outcomes. Author(s): Tutuian R, Castell DO. Source: Clinical Cornerstone. 2003; 5(4): 51-7; Discussion 58-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101495

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Gastroesophageal reflux disease: presentation and assessment of a common, challenging disorder. Author(s): Soll AH, Fass R. Source: Clinical Cornerstone. 2003; 5(4): 2-14; Discussion 14-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101491

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Gastroesophageal reflux disease: review of presenting symptoms, evaluation, management, and outcome in infants. Author(s): Tolia V, Wuerth A, Thomas R. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1723-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560991

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Gastroesophageal reflux disease: symptoms versus pH monitoring results. Author(s): Yorulmaz I, Ozlugedik S, Kucuk B. Source: Otolaryngology and Head and Neck Surgery. 2003 November; 129(5): 582-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595283

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H. pylori-infected gastroesophageal reflux disease patients harbor less virulent strains. Author(s): Fallone CA, Barkun AN. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 1065. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003394

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Head and neck manifestations of gastroesophageal reflux disease. Author(s): Ahuja V, Yencha MW, Lassen LF. Source: American Family Physician. 1999 September 1; 60(3): 873-80, 885-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10498113

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Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials. Author(s): Caro JJ, Salas M, Ward A. Source: Clinical Therapeutics. 2001 July; 23(7): 998-1017. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11519776

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Health care utilization after medical and surgical therapy for gastroesophageal reflux disease: a population-based study, 1996 to 2000. Author(s): Khaitan L, Ray WA, Holzman MD, Smalley WE. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 December; 138(12): 1356-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662539

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Health state utilities in gastroesophageal reflux disease patients with heartburn: a study in Germany and Sweden. Author(s): Kartman B, Gatz G, Johannesson M. Source: Medical Decision Making : an International Journal of the Society for Medical Decision Making. 2004 January-February; 24(1): 40-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15005953

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Health-related quality of life in primary care patients with gastroesophageal reflux disease. Author(s): Kaplan-Machlis B, Spiegler GE, Revicki DA. Source: The Annals of Pharmacotherapy. 1999 October; 33(10): 1032-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534213

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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 and gastroesophageal reflux disease. Author(s): Garrido Serrano A, Lepe Jimenez JA, Guerrero Igea FJ, Perianes Hernandez C. Source: Rev Esp Enferm Dig. 2003 November; 95(11): 788-90, 785-7. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640876

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Helicobacter pylori and gastroesophageal reflux disease. Author(s): Metz DC, Kroser JA. Source: Gastroenterology Clinics of North America. 1999 December; 28(4): 971-85, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695012

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Helicobacter pylori and gastroesophageal reflux disease: a complex organism in a complex host. Author(s): Schwizer W, Fox M. Source: Journal of Pediatric Gastroenterology and Nutrition. 2004 January; 38(1): 12-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676589

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Helicobacter pylori and gastroesophageal reflux disease: lack of influence of infection on twenty-four-hour esophageal pH monitoring and endoscopic findings. Author(s): Gisbert JP, de Pedro A, Losa C, Barreiro A, Pajares JM. Source: Journal of Clinical Gastroenterology. 2001 March; 32(3): 210-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246345

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Helicobacter pylori and gastroesophageal reflux disease: to treat or not to treat? Author(s): O'Connor HJ, O'Morain CA. Source: Scandinavian Journal of Gastroenterology. 2001 July; 36(7): 677-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11444465

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Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease. Author(s): Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L, Axon AT. Source: Gastroenterology. 2001 November; 121(5): 1120-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11677204

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Helicobacter pylori infection, pattern of gastritis, and symptoms in erosive and nonerosive gastroesophageal reflux disease. Author(s): Manes G, Mosca S, Laccetti M, Lioniello M, Balzano A. Source: Scandinavian Journal of Gastroenterology. 1999 July; 34(7): 658-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466875

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Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease. Author(s): Oberg S, Peters JH, Nigro JJ, Theisen J, Hagen JA, DeMeester SR, Bremner CG, DeMeester TR. Source: Archives of Surgery (Chicago, Ill. : 1960). 1999 July; 134(7): 722-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401822

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Helicobacter pylori: a debated factor in gastroesophageal reflux disease. Author(s): Sharma P. Source: Digestive Diseases (Basel, Switzerland). 2001; 19(2): 127-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549822

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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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Hiatus hernia and intrathoracic migration of esophagogastric junction in gastroesophageal reflux disease. Author(s): Mattioli S, D'Ovidio F, Pilotti V, Di Simone MP, Lugaresi ML, Bassi F, Brusori S. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1823-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561009

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Historical perspectives on the treatment of gastroesophageal reflux disease. Author(s): Modlin IM, Kidd M, Lye KD. Source: Gastrointest Endosc Clin N Am. 2003 January; 13(1): 19-55, Vii-Viii. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797425

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How often is coughing the presenting complaint in patients with gastroesophageal reflux disease? Author(s): Adelman AM, Hall LW. Source: The Journal of Family Practice. 2002 March; 51(3): 211. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978229

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Identifying patients with gastroesophageal reflux disease in a managed care organization. Author(s): Ofman JJ, Ryu S, Borenstein J, Kania S, Lee J, Grogg A, Farup C, Weingarten S. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 September 1; 58(17): 1607-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11556654

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Identifying patients with gastroesophageal reflux disease: validation of a practical screening tool. Author(s): Ofman JJ, Shaw M, Sadik K, Grogg A, Emery K, Lee J, Reyes E, Fullerton S. Source: Digestive Diseases and Sciences. 2002 August; 47(8): 1863-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184543

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Immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in gastroesophageal reflux disease. Author(s): Nishiyama Y, Koyama S, Andoh A, Moritani S, Kushima R, Fujiyama Y, Hattori T, Bamba T. Source: Journal of Gastroenterology. 2002; 37(11): 905-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483245

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Impact of proton pump inhibitor utilization patterns on gastroesophageal reflux disease-related costs. Author(s): Hall J, Dodd S, Durkin M, Sloan S. Source: Manag Care. 2002 July; 11(7 Suppl): 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12181872

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Improving health-related quality of life in patients with gastroesophageal reflux disease. Author(s): Crawley JA. Source: Director. 2004 Spring; 12(2): 89-93. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15106370

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In support of "step-up therapy" for gastroesophageal reflux disease. Author(s): Beck IT. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 503-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866309

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Ineffective esophageal motility is a primary motility disorder in gastroesophageal reflux disease. Author(s): Ho SC, Chang CS, Wu CY, Chen GH. Source: Digestive Diseases and Sciences. 2002 March; 47(3): 652-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11911355

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Inflammation and intestinal metaplasia of the gastric cardia: Helicobacter pylori, gastroesophageal reflux disease, or both. Author(s): Goldblum JR. Source: Digestive Diseases (Basel, Switzerland). 2000; 18(1): 14-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10729733

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Influence of spontaneous sleep positions on nighttime recumbent reflux in patients with gastroesophageal reflux disease. Author(s): Khoury RM, Camacho-Lobato L, Katz PO, Mohiuddin MA, Castell DO. Source: The American Journal of Gastroenterology. 1999 August; 94(8): 2069-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10445529

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Initial experience with the stretta procedure for the treatment of gastroesophageal reflux disease. Author(s): Richards WO, Scholz S, Khaitan L, Sharp KW, Holzman MD. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2001 October; 11(5): 267-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11642661

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Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. Author(s): Shaw MJ, Talley NJ, Beebe TJ, Rockwood T, Carlsson R, Adlis S, Fendrick AM, Jones R, Dent J, Bytzer P. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 52-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197287

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Initial validation of a questionnaire for detecting gastroesophageal reflux disease in epidemiological settings. Author(s): Manterola C, Munoz S, Grande L, Bustos L. Source: Journal of Clinical Epidemiology. 2002 October; 55(10): 1041-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12464381

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Integrated acidity and the pathophysiology of gastroesophageal reflux disease. Author(s): Gardner JD, Rodriguez-Stanley S, Robinson M. Source: The American Journal of Gastroenterology. 2001 May; 96(5): 1363-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11374669

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Intermittent and on-demand use of proton pump inhibitors in the management of symptomatic gastroesophageal reflux disease. Author(s): Bardhan KD. Source: The American Journal of Gastroenterology. 2003 March; 98(3 Suppl): S40-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644030

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Intestinal metaplasia in the distal esophagus and correlation with symptoms of gastroesophageal reflux disease. Author(s): Dietz J, Meurer L, Maffazzoni DR, Furtado AD, Prolla JC. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2003; 16(1): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581251

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Intractable hiccup: an odd complication after laparoscopic fundoplication for gastroesophageal reflux disease. Author(s): Strate T, Langwieler TE, Mann O, Knoefel WT, Izbicki JR. Source: Surgical Endoscopy. 2002 July; 16(7): 1109. Epub 2002 April 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165833

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Is analysis of lower esophageal sphincter vector volumes of value in diagnosing gastroesophageal reflux disease? Author(s): Marsh RE, Perdue CL, Awad ZT, Watson P, Selima M, Davis RE, Filipi CJ. Source: World Journal of Gastroenterology : Wjg. 2003 January; 9(1): 174-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508377

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Is Helicobacter pylori eradication associated with gastroesophageal reflux disease? Author(s): Fallone CA, Barkun AN, Friedman G, Mayrand S, Loo V, Beech R, Best L, Joseph L. Source: The American Journal of Gastroenterology. 2000 April; 95(4): 914-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10763937

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Is laparoscopic antireflux surgery for gastroesophageal reflux disease in the elderly safe and effective? Author(s): Brunt LM, Quasebarth MA, Dunnegan DL, Soper NJ. Source: Surgical Endoscopy. 1999 September; 13(9): 838-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10449835

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Lansoprazole in adolescents with gastroesophageal reflux disease: pharmacokinetics, pharmacodynamics, symptom relief efficacy, and tolerability. Author(s): Gunasekaran T, Gupta S, Gremse D, Karol M, Pan WJ, Chiu YL, Keith R, Fitzgerald J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002; 35 Suppl 4: S327-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607793

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Lansoprazole: in the management of gastroesophageal reflux disease in children. Author(s): Scott LJ. Source: Paediatric Drugs. 2003; 5(1): 57-61; Discussion 62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12513106

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Laparoscopic antireflux surgery and its effect on cough in patients with gastroesophageal reflux disease. Author(s): Thoman DS, Hui TT, Spyrou M, Phillips EH. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 January-February; 6(1): 17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986013

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Laparoscopic antireflux surgery for gastroesophageal reflux disease: experience with 668 laparoscopic antireflux procedures. Author(s): Granderath FA, Kamolz T, Schweiger UM, Pointner R. Source: International Journal of Colorectal Disease. 2003 January; 18(1): 73-7. Epub 2002 May 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458385

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Laparoscopic antireflux surgery for supraesophageal complications of gastroesophageal reflux disease. Author(s): Klaus A, Swain JM, Hinder RA. Source: The American Journal of Medicine. 2001 December 3; 111 Suppl 8A: 202S-206S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11749951

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Laparoscopic antireflux surgery with routine mesh-hiatoplasty in the treatment of gastroesophageal reflux disease. Author(s): Granderath FA, Schweiger UM, Kamolz T, Pasiut M, Haas CF, Pointner R. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 May-June; 6(3): 347-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022986

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Laparoscopic fundoplication in mentally normal children with gastroesophageal reflux disease. Author(s): Menon KV, Booth M, Stratford J, Dehn TC. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(2): 163-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220426

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Laparoscopic gastric fundoplication for treatment of gastroesophageal reflux disease (GERD). Results from 150 consecutive cases. Author(s): Graber J, Dunn D, Johnson E, Alden P, Bretzke M, Markman J. Source: Minn Med. 2002 January; 85(1): 38-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12793231

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Laparoscopic Roux-en-Y gastric bypass for recalcitrant gastroesophageal reflux disease in morbidly obese patients. Author(s): Perry Y, Courcoulas AP, Fernando HC, Buenaventura PO, McCaughan JS, Luketich JD. Source: Jsls. 2004 January-March; 8(1): 19-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14974657

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Laparoscopic surgery for gastroesophageal reflux disease and paraesophageal hernia. Author(s): Dalvi AN, Thapar PM, Agrawal JB. Source: Indian J Gastroenterol. 2002 July-August; 21(4): 133-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385538

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Laparoscopic surgery for gastroesophageal reflux disease patients with impaired esophageal peristalsis: total or partial fundoplication? Author(s): Chrysos E, Tsiaoussis J, Zoras OJ, Athanasakis E, Mantides A, Katsamouris A, Xynos E. Source: Journal of the American College of Surgeons. 2003 July; 197(1): 8-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12831918

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Laparoscopic Toupet versus Nissen fundoplication for the treatment of gastroesophageal reflux disease. Author(s): Erenoglu C, Miller A, Schirmer B. Source: Int Surg. 2003 October-December; 88(4): 219-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717528

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Laryngeal manifestations of gastroesophageal reflux disease in children. Author(s): Zalesska-Krecicka M, Krecicki T, Iwanczak B, Blitek A, Horobiowska M. Source: Acta Oto-Laryngologica. 2002 April; 122(3): 306-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030580

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Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Author(s): Vaezi MF, Hicks DM, Abelson TI, Richter JE. Source: Clin Gastroenterol Hepatol. 2003 September; 1(5): 333-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017651

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Laryngitis and gastroesophageal reflux disease: increasing prevalence or poor diagnostic tests? Author(s): Vaezi MF. Source: The American Journal of Gastroenterology. 2004 May; 99(5): 786-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128337

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Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease. Author(s): Koufman JA. Source: Ear, Nose, & Throat Journal. 2002 September; 81(9 Suppl 2): 7-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353431

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Laryngospasm: an atypical manifestation of severe gastroesophageal reflux disease (GERD). Author(s): Maceri DR, Zim S. Source: The Laryngoscope. 2001 November; 111(11 Pt 1): 1976-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801981

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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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Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. Author(s): Spechler SJ, Lee E, Ahnen D, Goyal RK, Hirano I, Ramirez F, Raufman JP, Sampliner R, Schnell T, Sontag S, Vlahcevic ZR, Young R, Williford W. Source: Jama : the Journal of the American Medical Association. 2001 May 9; 285(18): 2331-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343480

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Lung transplantation exacerbates gastroesophageal reflux disease. Author(s): Young LR, Hadjiliadis D, Davis RD, Palmer SM. Source: Chest. 2003 November; 124(5): 1689-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605036

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Managed care issues in the treatment of gastroesophageal reflux disease. Author(s): DeVault KR. Source: Am J Manag Care. 2000 October; 6(16 Suppl): S871-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11184657

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Management of gastroesophageal reflux disease in primary care: results of a survey in 2 areas in Germany. Author(s): Meining A, Driesnack U, Classen M, Rosch T. Source: Zeitschrift Fur Gastroenterologie. 2002 January; 40(1): 15-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11803496

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Management of gastroesophageal reflux disease. Author(s): Tutuian R, Castell DO. Source: The American Journal of the Medical Sciences. 2003 November; 326(5): 309-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615672

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Management of gastroesophageal reflux disease. Author(s): Heidelbaugh JJ, Nostrant TT, Kim C, Van Harrison R. Source: American Family Physician. 2003 October 1; 68(7): 1311-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567485

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Management of patients with gastroesophageal reflux disease and esophageal or gastric dysmotility. Author(s): Swanstrom LL. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2001 September-October; 5(5): 448-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11985993

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Management of patients with symptomatic gastroesophageal reflux disease: a primary care perspective. Author(s): Fendrick AM. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510767

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Management of respiratory symptoms associated with gastroesophageal reflux disease. Author(s): Greason KL, Miller DL. Source: Minerva Chir. 2002 December; 57(6): 781-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592220

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Management of severe gastroesophageal reflux disease. Author(s): DiPalma JA. Source: Journal of Clinical Gastroenterology. 2001 January; 32(1): 19-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11154163

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Managing gastroesophageal reflux disease. Author(s): Ray SW, Secrest J, Ch'ien AP, Corey RS. Source: The Nurse Practitioner. 2002 May; 27(5): 36-53; Quiz 54-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037474

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Managing gastroesophageal reflux disease: from pharmacology to the clinical arena. Author(s): Wolfe MM. Source: Gastroenterology Clinics of North America. 2003 September; 32(3 Suppl): S37-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556434

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Measuring symptom distress and health-related quality of life in clinical trials of gastroesophageal reflux disease treatment: further validation of the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS). Author(s): Damiano A, Handley K, Adler E, Siddique R, Bhattacharyja A. Source: Digestive Diseases and Sciences. 2002 July; 47(7): 1530-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12141813

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Mechanisms of gastroesophageal reflux and gastroesophageal reflux disease. Author(s): Vandenplas Y, Hassall E. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 August; 35(2): 119-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187285

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Medical management of gastroesophageal reflux disease. Author(s): Ferraro P, Duranceau A. Source: Chest Surg Clin N Am. 2001 August; 11(3): 517-22, Vi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11787963

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Medical management of patients with esophageal or supraesophageal gastroesophageal reflux disease. Author(s): Richter JE. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 179S-187S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928099

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Medical therapy for gastroesophageal reflux disease. Author(s): Arora AS, Castell DO. Source: Mayo Clinic Proceedings. 2001 January; 76(1): 102-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11155401

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Medical treatment of supraesophageal complications of gastroesophageal reflux disease. Author(s): Hogan WJ, Shaker R. Source: The American Journal of Medicine. 2001 December 3; 111 Suppl 8A: 197S-201S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11749950

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Medical, surgical, and endoscopic treatment of gastroesophageal reflux disease and Barrett's esophagus. Author(s): Castell DO. Source: Journal of Clinical Gastroenterology. 2001 October; 33(4): 262-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588538

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Minimally invasive surgery for gastroesophageal reflux disease. Author(s): Oelschlager BK, Pellegrini CA. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2001 December; 11(6): 341-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814124

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Minimally invasive surgical techniques in reoperative surgery for gastroesophageal reflux disease in infants and children. Author(s): Tan S, Wulkan ML. Source: The American Surgeon. 2002 November; 68(11): 989-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455792

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Modern imaging for the assessment of gastroesophageal reflux disease begins with the barium esophagram. Author(s): Peters JH. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2000 July-August; 4(4): 346-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185452

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Natural course of gastroesophageal reflux disease: 17-22 year follow-up of 60 patients. Author(s): Isolauri J, Luostarinen M, Isolauri E, Reinikainen P, Viljakka M, Keyrilainen O. Source: The American Journal of Gastroenterology. 1997 January; 92(1): 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8995934

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Natural history of gastroesophageal reflux disease and functional abdominal disorders: a population-based study. Author(s): Agreus L, Svardsudd K, Talley NJ, Jones MP, Tibblin G. Source: The American Journal of Gastroenterology. 2001 October; 96(10): 2905-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11693325

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Natural history of nonerosive reflux disease. Is all gastroesophageal reflux disease the same? What is the evidence? Author(s): Locke GR 3rd. Source: Gastroenterology Clinics of North America. 2002 December; 31(4 Suppl): S59-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489471

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New alternatives in the management of gastroesophageal reflux disease. Author(s): Oleynikov D, Oelschlager B. Source: American Journal of Surgery. 2003 August; 186(2): 106-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885599

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New concepts and methods in the study and treatment of gastroesophageal reflux disease. Author(s): Johnson LF. Source: The Medical Clinics of North America. 1981 November; 65(6): 1195-222. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7035765

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Newer therapies for gastroesophageal reflux disease: numb, burn, or stitch? Author(s): Jailwala J, Shaker R. Source: Current Gastroenterology Reports. 2001 June; 3(3): 188-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11353553

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Nissen fundoplication for gastroesophageal reflux disease in infants and children. Author(s): Fonkalsrud EW. Source: Semin Pediatr Surg. 1998 May; 7(2): 110-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9597703

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Nissen fundoplication for gastroesophageal reflux disease. Evaluation of primary repair in 100 consecutive patients. Author(s): DeMeester TR, Bonavina L, Albertucci M. Source: Annals of Surgery. 1986 July; 204(1): 9-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3729589

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Nizatidine versus placebo in gastroesophageal reflux disease. A six-week, multicenter, randomized, double-blind comparison. Nizatidine Gastroesophageal Reflux Disease Study Group. Author(s): Cloud ML, Offen WW. Source: Digestive Diseases and Sciences. 1992 June; 37(6): 865-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1587191

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Nizatidine versus placebo in gastroesophageal reflux disease: a 12-week, multicenter, randomized, double-blind study. Author(s): Cloud ML, Offen WW, Robinson M. Source: The American Journal of Gastroenterology. 1991 December; 86(12): 1735-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1962618

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Nizatidine versus placebo in gastro-oesophageal reflux disease: a 6-week, multicentre, randomised, double-blind comparison. Nizatidine Gastroesophageal Reflux Disease Study Group. Author(s): Cloud ML, Offen WW. Source: Br J Clin Pract Suppl. 1994 November; 76: 11-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7794700

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No association between gallstones and gastroesophageal reflux disease. Author(s): Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Source: The American Journal of Gastroenterology. 2001 October; 96(10): 2858-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11693317

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Nonobstructive dysphagia in gastroesophageal reflux disease: a study with combined ambulatory pH and motility monitoring. Author(s): Singh S, Stein HJ, DeMeester TR, Hinder RA. Source: The American Journal of Gastroenterology. 1992 May; 87(5): 562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1595641

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Not the perfect study, but helpful wisdom for treating asthma patients with gastroesophageal reflux disease. Author(s): Richter JE. Source: Chest. 2003 April; 123(4): 973-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684276

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Novel medical therapies for gastroesophageal reflux disease beyond proton-pump inhibitors. Author(s): Richter JE. Source: Gastroenterology Clinics of North America. 2002 December; 31(4 Suppl): S111-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489476

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Omeprazole maintenance therapy for gastroesophageal reflux disease after failure of fundoplication. Author(s): Pashankar D, Blair GK, Israel DM. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 February; 32(2): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11321383

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One-week esomeprazole treatment: an effective confirmatory test in patients with suspected gastroesophageal reflux disease. Author(s): Johnsson F, Hatlebakk JG, Klintenberg AC, Roman J, Toth E, Stubberod A, Falk A, Edin R. Source: Scandinavian Journal of Gastroenterology. 2003 April; 38(4): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739706

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Optimizing medical therapy for gastroesophageal reflux disease: state of the art. Author(s): Katz PO. Source: Reviews in Gastroenterological Disorders. 2003 Spring; 3(2): 59-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776003

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Oral and intravenous dosage forms of pantoprazole are equivalent in their ability to suppress gastric acid secretion in patients with gastroesophageal reflux disease. Author(s): Metz DC, Pratha V, Martin P, Paul J, Maton PN, Lew E, Pisegna JR. Source: The American Journal of Gastroenterology. 2000 March; 95(3): 626-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710049

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Outcome of laparoscopic anterior 180-degree partial fundoplication for gastroesophageal reflux disease. Author(s): Csendes A. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2001 July-August; 5(4): 445; Author Reply 445-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11985990

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Outcomes after minimally invasive reoperation for gastroesophageal reflux disease. Author(s): Luketich JD, Fernando HC, Christie NA, Buenaventura PO, Ikramuddin S, Schauer PR. Source: The Annals of Thoracic Surgery. 2002 August; 74(2): 328-31; Discussion 331-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173808

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Outcomes of laparoscopic fundoplication for gastroesophageal reflux disease and paraesophageal hernia. Author(s): Terry M, Smith CD, Branum GD, Galloway K, Waring JP, Hunter JG. Source: Surgical Endoscopy. 2001 July; 15(7): 691-9. Epub 2001 May 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591970

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Outcomes of pediatric gastroesophageal reflux disease: in the first year of life, in childhood, and in adults.oh, and should we really leave Helicobacter pylori alone? Author(s): Gold BD. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November-December; 37 Suppl 1: S33-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685076

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Overview of medical therapy for gastroesophageal reflux disease. Author(s): DeVault KR. Source: Gastroenterology Clinics of North America. 1999 December; 28(4): 831-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695004

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Overview of pediatric gastroesophageal reflux disease and proton pump inhibitor therapy. Author(s): Colletti RB, Di Lorenzo C. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November-December; 37 Suppl 1: S7-S11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685071

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Pathogenesis of gastroesophageal reflux disease. Author(s): Orlando RC. Source: The American Journal of the Medical Sciences. 2003 November; 326(5): 274-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615668

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Pathogenesis of gastroesophageal reflux disease. Author(s): Orlando RC. Source: Gastroenterology Clinics of North America. 2002 December; 31(4 Suppl): S35-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489469

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Pathological basis of gastroesophageal reflux disease. Author(s): Chandrasoma P. Source: World Journal of Surgery. 2003 September; 27(9): 986-93. Epub 2003 July 17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560363

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Pathophysiological measurement and results after laparoscopic fundoplication for gastroesophageal reflux disease. Author(s): Ludwig K, Bernhardt J, Amtsberg G, Patrzyk M, Wilhelm L, Hoene A. Source: Surgery Today. 2003; 33(2): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616367

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Pediatric gastroesophageal reflux disease--current perspectives. Author(s): Strople J, Kaul A. Source: Current Opinion in Otolaryngology & Head and Neck Surgery. 2003 December; 11(6): 447-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631177

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Perianesthesia care of the patient with gastroesophageal reflux disease. Author(s): Redmond MC. Source: Journal of Perianesthesia Nursing : Official Journal of the American Society of Perianesthesia Nurses / American Society of Perianesthesia Nurses. 2003 October; 18(5): 335-44; Quiz 345-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14569544

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Persistent gastroesophageal reflux disease symptoms on standard proton-pump inhibitor therapy. Author(s): Sontag SJ. Source: Gastroenterology Clinics of North America. 2002 December; 31(4 Suppl): S77-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489473

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Pharmacokinetics and pharmacodynamics of lansoprazole in children with gastroesophageal reflux disease. Author(s): Gremse D, Winter H, Tolia V, Gunasekaran T, Pan WJ, Karol M, Chiu YL, Pilmer B, Book L. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002; 35 Suppl 4: S319-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607792

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Pharmacokinetics of a single oral dose of baclofen in pediatric patients with gastroesophageal reflux disease. Author(s): Wiersma HE, van Boxtel CJ, Butter JJ, van Aalderen WM, Omari T, Benninga MA. Source: Therapeutic Drug Monitoring. 2003 February; 25(1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548151

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Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease. Author(s): Marier JF, Dubuc MC, Drouin E, Alvarez F, Ducharme MP, Brazier JL. Source: Therapeutic Drug Monitoring. 2004 February; 26(1): 3-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749542

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Quality of life after antireflux surgery compared with nonoperative management for severe gastroesophageal reflux disease. Author(s): Fernando HC, Schauer PR, Rosenblatt M, Wald A, Buenaventura P, Ikramuddin S, Luketich JD. Source: Journal of the American College of Surgeons. 2002 January; 194(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11800337

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Quality of life and surgical outcome after laparoscopic antireflux surgery in the elderly gastroesophageal reflux disease patient. Author(s): Kamolz T, Bammer T, Granderath FA, Pasiut M, Pointner R. Source: Scandinavian Journal of Gastroenterology. 2001 February; 36(2): 116-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11252401

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Quality of life and symptomatic outcome three to five years after laparoscopic Toupet fundoplication in gastroesophageal reflux disease patients with impaired esophageal motility. Author(s): Granderath FA, Kamolz T, Schweiger UM, Pasiut M, Wykypiel H Jr, Pointner R. Source: American Journal of Surgery. 2002 February; 183(2): 110-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918872

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Quality of life for patients with gastroesophageal reflux disease 2 years after laparoscopic fundoplication. Evaluation of the results obtained during the initial experience. Author(s): Contini S, Bertele A, Nervi G, Zinicola R, Scarpignato C. Source: Surgical Endoscopy. 2002 November; 16(11): 1555-60. Epub 2002 June 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072998

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Quality of life for patients with gastroesophageal reflux disease. Author(s): Kamolz T. Source: Surgical Endoscopy. 2003 April; 17(4): 664; Author Reply 665. Epub 2003 February 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698333

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Quality of life in patients with gastroesophageal reflux disease. Author(s): Wiklund I. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S46-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510771

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Quality of life scale for gastroesophageal reflux disease. Author(s): Velanovich V, Vallance SR, Gusz JR, Tapia FV, Harkabus MA. Source: Journal of the American College of Surgeons. 1996 September; 183(3): 217-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8784314

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Rabeprazole improves health-related quality of life in patients with erosive gastroesophageal reflux disease. Author(s): Johanson JF, Siddique R, Damiano AM, Jokubaitis L, Murthy A, Bhattacharjya A. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2574-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452397

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Reductions in symptom distress reported by patients with moderately severe, nonerosive gastroesophageal reflux disease treated with rabeprazole. Author(s): Damiano A, Siddique R, Xu X, Johanson J, Sloan S. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 657-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741452

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Reflex mechanisms in gastroesophageal reflux disease and asthma. Author(s): Canning BJ, Mazzone SB. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 45S-48S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928074

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Regulation of Na/H exchanger-1 in gastroesophageal reflux disease: possible interaction of histamine receptor. Author(s): Siddique I, Khan I. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1832-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561010

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Relationship between Helicobacter pylori infection and erosive gastroesophageal reflux disease. Author(s): Wu CH, Wu MS, Huang SP, Lin JT. Source: J Formos Med Assoc. 2004 March; 103(3): 186-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15124045

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Relationship of gastroesophageal reflux disease with adenocarcinoma of the distal esophagus and cardia. Author(s): Velanovich V, Hollingsworth J, Suresh P, Ben-Menachem T. Source: Digestive Surgery. 2002; 19(5): 349-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435904

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Relationship of sliding hiatus hernia to gastroesophageal reflux disease: a possible role for Helicobacter pylori infection? Author(s): Manes G, Pieramico O, Uomo G, Mosca S, de Nucci C, Balzano A. Source: Digestive Diseases and Sciences. 2003 February; 48(2): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643607

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Report of the Asia-Pacific consensus on the management of gastroesophageal reflux disease. Author(s): Fock KM, Talley N, Hunt R, Fass R, Nandurkar S, Lam SK, Goh KL, Sollano J. Source: Journal of Gastroenterology and Hepatology. 2004 April; 19(4): 357-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15012771

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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 manometry and pH-metry in patients with symptoms and signs of gastroesophageal reflux disease. Author(s): Bresadola V, Dado G, Terrosu G, Alessandrini V, Marcellino MG, Bresadola F. Source: Chir Ital. 2003 November-December; 55(6): 785-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725217

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Safety and efficacy of rabeprazole in gastroesophageal reflux disease: report of a multicenter study. Author(s): Kar P, Chandrashekar N, Devi S, Bhatia SJ, Alvares JF, Taneja A, Towar A. Source: Indian J Gastroenterol. 2003 July-August; 22(4): 153. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962446

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Selection of patients with gastroesophageal reflux disease for antireflux surgery based on esophageal manometry. Author(s): Klaus A, Gadenstaetter M, Muhlmann G, Kirchmayr W, Profanter C, Achem SR, Wetscher GJ. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1719-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560990

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Severity of gastroesophageal reflux disease influences daytime somnolence: a clinical study of 134 patients underwent upper panendoscopy. Author(s): Demeter P, Visy KV, Gyulai N, Sike R, Toth TG, Novak J, Magyar P. Source: World Journal of Gastroenterology : Wjg. 2004 June 15; 10(12): 1798-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188509

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Short-term treatment of gastroesophageal reflux disease. Author(s): van Pinxteren B, Numans ME, Lau J, de Wit NJ, Hungin AP, Bonis PA. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2003 September; 18(9): 755-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950485

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Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Author(s): Numans ME, Lau J, de Wit NJ, Bonis PA. Source: Annals of Internal Medicine. 2004 April 6; 140(7): 518-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068979

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Sleep issues in gastroesophageal reflux disease: beyond simple heartburn control. Author(s): Orr WC. Source: Reviews in Gastroenterological Disorders. 2003; 3 Suppl 4: S22-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671511

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Soothing the burn. Management of gastroesophageal reflux disease. Author(s): Kempf WI. Source: Adv Nurse Pract. 2004 January; 12(1): 47-50. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730836

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Stomach myoelectrical response of patients with gastroesophageal reflux disease receiving omeprazole treatment. Author(s): Chang FY, Lu CL, Chen CY, Luo JC, Jiun KL, Lee SD, Wu HC. Source: Journal of Gastroenterology and Hepatology. 2003 December; 18(12): 1399-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675269

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Stretta procedure for the treatment of gastroesophageal reflux disease. Author(s): McCormick DG. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2004 January-February; 27(1): 22-8; Quiz 29-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15075961

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Stretta: an effective, minimally invasive treatment for gastroesophageal reflux disease. Author(s): Triadafilopoulos G. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 192S-200S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928101

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Temporal correlation between chronic cough and gastroesophageal reflux disease. Author(s): Wunderlich AW, Murray JA. Source: Digestive Diseases and Sciences. 2003 June; 48(6): 1050-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12822861

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The association of gastroesophageal reflux disease with asthma and chronic cough in the adult. Author(s): Theodoropoulos DS, Pecoraro DL, Efstratiadis SE. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2002; 1(2): 133-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720067

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The epidemiology of gastroesophageal reflux disease. Author(s): Shaheen N, Provenzale D. Source: The American Journal of the Medical Sciences. 2003 November; 326(5): 264-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615667

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The history and future of implantation therapy for gastroesophageal reflux disease. Author(s): Lehman GA. Source: Gastrointest Endosc Clin N Am. 2003 January; 13(1): 157-65, Xi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797435

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The impact of gastroesophageal reflux disease on quality of life. Author(s): Kamolz T, Pointner R, Velanovich V. Source: Surgical Endoscopy. 2003 August; 17(8): 1193-9. Epub 2003 June 13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799881

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The role of proton pump inhibitors in the management of gastroesophageal reflux disease-related asthma and chronic cough. Author(s): Kiljander TO. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 65S-71S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928078

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The surgical management of gastroesophageal reflux disease. Author(s): Migliori SJ. Source: Medicine and Health, Rhode Island. 2004 February; 87(2): 33-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031962

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Therapy for gastroesophageal reflux disease: more is not necessarily better. Author(s): Metz DC. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1913-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499765

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Transesophageal endoscopic treatments for gastroesophageal reflux disease. Author(s): TEC Assessment Program, Blue Cross Blue Shield Association. Source: Technol Eval Cent Asses Program Exec Summ. 2004 February; 18(20): 1-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15241901

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Treatment of gastroesophageal reflux disease. Author(s): Fass R, Bautista J, Janarthanan S. Source: Clinical Cornerstone. 2003; 5(4): 18-29; Discussion 30-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101492

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Understanding gastroesophageal reflux disease. Author(s): Rayhorn N, Argel N, Demchak K. Source: Nursing. 2003 October; 33(10): 36-41; Quiz 41-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528123

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Up to date. Gastroesophageal reflux disease (GERD) influence of obesity. Author(s): Chiocca JC. Source: Acta Gastroenterol Latinoam. 2002; 32(2): 95-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553162

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Update on gastroesophageal reflux disease in pediatric airway disorders. Author(s): Yellon RF, Goldberg H. Source: The American Journal of Medicine. 2001 December 3; 111 Suppl 8A: 78S-84S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11749930

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Upright versus supine reflux in gastroesophageal reflux disease. Author(s): Ouatu-Lascar R, Lin OS, Fitzgerald RC, Triadafilopoulos G. Source: Journal of Gastroenterology and Hepatology. 2001 November; 16(11): 1184-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903733

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Use of healthcare resources among medically and surgically treated patients with gastroesophageal reflux disease: a population-based study. Author(s): Holzman MD, Mitchel EF, Ray WA, Smalley WE. Source: Journal of the American College of Surgeons. 2001 January; 192(1): 17-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11192919

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Use of MIB-1 in the assessment of esophageal biopsy specimens from patients with gastroesophageal reflux disease in well- and poorly oriented areas. Author(s): Haber MM, Lu L, Modi A, Garcia FU. Source: Applied Immunohistochemistry & Molecular Morphology : Aimm / Official Publication of the Society for Applied Immunohistochemistry. 2002 June; 10(2): 128-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12051630

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Use of radiofrequency ablation of the lower esophageal sphincter to treat recurrent gastroesophageal reflux disease. Author(s): Islam S, Geiger JD, Coran AG, Teitelbaum DH. Source: Journal of Pediatric Surgery. 2004 March; 39(3): 282-6; Discussion 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017538

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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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Utility and willingness to pay measurements among patients with gastroesophageal reflux disease. Author(s): Kartman B. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S38-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510769

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Vagotomy, antrectomy, and Roux-en-Y diversion for complex reoperative gastroesophageal reflux disease. Author(s): Ellis FH Jr, Gibb SP. Source: Annals of Surgery. 1994 October; 220(4): 536-42; Discussion 542-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7944663

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Validation of the GSFQ, a self-administered symptom frequency questionnaire for patients with gastroesophageal reflux disease. Author(s): Pare P, Meyer F, Armstrong D, Pyzyk M, Pericak D, Goeree R. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 May; 17(5): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772004

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Value of a therapeutic trial to diagnose gastroesophageal reflux disease: step up versus step down therapy. Author(s): Da Costa LR. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 1997 September; 11 Suppl B: 78B-81B. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9347183

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Value of pH probe testing in pediatric patients with extraesophageal manifestations of gastroesophageal reflux disease: a retrospective review. Author(s): Bauman NM, Bishop WP, Sandler AD, Smith RJ. Source: Ann Otol Rhinol Laryngol Suppl. 2000 October; 184: 18-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11051426

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Viral mutants and fulminant hepatitis. Extraesophageal associations of gastroesophageal reflux disease in children without neurologic defects. Author(s): Orenstein SR. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 April; 34(4): 427-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981953

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Voice disorders in children with gastroesophageal reflux disease. Author(s): Niedzielska G, Glijer E, Toman D, Kudlicka A. Source: Ann Univ Mariae Curie Sklodowska [med]. 2000; 55: 91-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11482113

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What do we know about gastroesophageal reflux disease? Author(s): Bloom BS, Glise H. Source: The American Journal of Gastroenterology. 2001 August; 96(8 Suppl): S1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510762

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What is the best treatment for patients with severe gastroesophageal reflux disease (GERD)? Author(s): Henley E, Chang L. Source: The Journal of Family Practice. 2001 August; 50(8): 656. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509155

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What outcome measures are needed to assess gastroesophageal reflux disease in children? what study design is appropriate? what new knowledge is needed? Author(s): Gold BD, Co J, Colletti RB, Euler AR, Ferris TG, Fitzgerald JF, Flores AF, Gallo-Torres H, Orenstein SR, Rodriguez WJ, Willging P. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November-December; 37 Suppl 1: S72-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685083

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Which patients with gastroesophageal reflux disease (GERD) should have esophagogastroduoudenoscopy (EGD)? Author(s): Danis P. Source: The Journal of Family Practice. 2001 August; 50(8): 658-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509157

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Whither surgery in the treatment of gastroesophageal reflux disease (GERD)? Author(s): Urbach DR, Ungar WJ, Rabeneck L. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2004 January 20; 170(2): 219-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734435

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Willingness to pay for complete symptom relief of gastroesophageal reflux disease. Author(s): Kleinman L, McIntosh E, Ryan M, Schmier J, Crawley J, Locke GR 3rd, De Lissovoy G. Source: Archives of Internal Medicine. 2002 June 24; 162(12): 1361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076234

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Work loss costs due to peptic ulcer disease and gastroesophageal reflux disease in a health maintenance organization. Author(s): Henke CJ, Levin TR, Henning JM, Potter LP. Source: The American Journal of Gastroenterology. 2000 March; 95(3): 788-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710076

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Workshop consensus report on the extraesophageal complications of gastroesophageal reflux disease. Author(s): Johnson DA. Source: Journal of Clinical Gastroenterology. 2000 April; 30(3 Suppl): S51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10777175

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Wrap session: is the Nissen slipping? Can medical treatment replace surgery for severe gastroesophageal reflux disease in children? Author(s): Hassall E. Source: The American Journal of Gastroenterology. 1995 August; 90(8): 1212-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7639217

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Wrong-way swallowing as a possible cause of bronchitis in patients with gastroesophageal reflux disease. Author(s): Tibbling L. Source: Acta Oto-Laryngologica. 1993 May; 113(3): 405-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8517146

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CHAPTER 2.

NUTRITION AND GASTROESOPHAGEAL REFLUX DISEASE

Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and gastroesophageal reflux disease.

Finding Nutrition Studies on Gastroesophageal Reflux Disease The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “gastroesophageal reflux disease” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

Clinical and humanistic outcomes in patients with gastroesophageal reflux disease converted from omeprazole to lansoprazole. Author(s): Center for Drug Policy and Clinical Economics, University of Wisconsin Hospital and Clinics, 600 Highland Ave, 1530, CSC F6/133, Madison, WI 53792, USA. [email protected] Source: Nelson, W W Vermeulen, L C Geurkink, E A Ehlert, D A Reichelderfer, M ArchIntern-Med. 2000 September 11; 160(16): 2491-6 0003-9926

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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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Improvement of gastroesophageal reflux disease after initiation of a lowcarbohydrate diet: five brief case reports. Author(s): Center for Health Services Research in Primary Care, Veterans' Affairs Medical Center, Division of General Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, USA. Source: Yancy, W S Jr Provenzale, D Westman, E C Altern-Ther-Health-Med. 2001 NovDecember; 7(6): 120, 116-9 1078-6791

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Overweight, but not high dietary fat intake, increases risk of gastroesophageal reflux disease hospitalization: the NHANES I Epidemiologic Followup Study. First National Health and Nutrition Examination Survey. Author(s): Social and Scientific Systems, Inc., Bethesda, MD 20814-4805, USA. Source: Ruhl, C E Everhart, J E Ann-Epidemiol. 1999 October; 9(7): 424-35 1047-2797

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Randomised controlled trial of pantoprazole versus ranitidine for the treatment of uninvestigated heartburn in primary care. Author(s): University of Sydney, Nepean Hospital, PO Box 63, Penrith, NSW 2751, Australia. [email protected] Source: Talley, N J Moore, M G Sprogis, A Katelaris, P Med-J-Aust. 2002 October 21; 177(8): 423-7 0025-729X

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The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children. Author(s): Division of Pediatric Gastroenterology, University of Pittsburgh School of Medicine, and Children's Hospital of Pittsburgh, Pennsylvania 15213, USA. Source: Orenstein, S R Shalaby, T M Di Lorenzo, C Putnam, P E Sigurdsson, L Kocoshis, S A Am-J-Gastroenterol. 2000 June; 95(6): 1422-30 0002-9270

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Treatment of advanced gastroesophageal reflux disease with Collis gastroplasty and Belsey partial fundoplication. Author(s): Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033-4612, USA. Source: Ritter, M P Peters, J H DeMeester, T R Gadenstatter, M Oberg, S Fein, M Hagen, J A Crookes, P F Bremner, C G Arch-Surg. 1998 May; 133(5): 523-8; discussion 528-9 0004-0010

Nutrition

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Usage of supplemental alternative medicine by community-based patients with gastroesophageal reflux disease (GERD). Author(s): Southem Arizona VA Health Care System and University of Arizona Health Sciences Center, Department of Medicine, Tucson 85723, USA. Source: Hayden, Craig W Bernstein, Charles N Hall, Renee A Vakil, Nimish Garewal, Harinder S Fass, Ronnie Dig-Dis-Sci. 2002 January; 47(1): 1-8 0163-2116

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

•

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/

•

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

•

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

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

Vitamins Pantothenic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,882,00.html Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html

•

Minerals Betaine Hydrochloride Source: Healthnotes, Inc.; www.healthnotes.com Betaine Hydrochloride Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Lecithin and Choline Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10040,00.html Quercetin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10053,00.html

•

Food and Diet Chocolate Source: Healthnotes, Inc.; www.healthnotes.com Cinnamon Alternative names: Cinnamomum zeylanicum Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Coffee Source: Healthnotes, Inc.; www.healthnotes.com Garlic Alternative names: Allium sativum Source: Healthnotes, Inc.; www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Garlic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html Juices Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND GASTROESOPHAGEAL REFLUX DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to gastroesophageal reflux disease. 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 gastroesophageal reflux disease 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 “gastroesophageal reflux disease” (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 gastroesophageal reflux disease: •

“Silent” regurgitation and aspiration during general anesthesia. Author(s): Blitt CD, Gutman HL, Cohen DD, Weisman H, Dillon JB. Source: Anesthesia and Analgesia. 1970 September-October; 49(5): 707-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5534428

•

A 16-month-old with persistent vomiting. Author(s): Palumbo M, Dolen WK, Good RA. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 April; 90(4): 380-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12722957

•

A case of feet. Author(s): Wilson A.

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Source: Aust Coll Midwives Inc J. 1995 March; 8(1): 17-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7619012 •

A depressed, ataxic, and regurgitating Pacific Parrotlet. Diagnosis: acute lead poisoning. Author(s): Brown C. Source: Lab Anim (Ny). 2002 June; 31(6): 23-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040380

•

A rapid intubation technique for prevention of aspiration during induction of anaesthesia. Author(s): Khawaja AA. Source: British Journal of Anaesthesia. 1971 October; 43(10): 980-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5115034

•

A systematic review of nonpharmacological and nonsurgical therapies for gastroesophageal reflux in infants. Author(s): Carroll AE, Garrison MM, Christakis DA. Source: Archives of Pediatrics & Adolescent Medicine. 2002 February; 156(2): 109-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814369

•

A yoga teacher with persistent reflux symptoms. Author(s): Biswas R, Paul A, Shetty KJ. Source: Int J Clin Pract. 2002 November; 56(9): 723. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469992

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An investigation into the efficacy of the pectin based anti-reflux formulation-Aflurax. Author(s): Waterhouse ET, Washington C, Washington N. Source: International Journal of Pharmaceutics. 2000 November 19; 209(1-2): 79-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084248

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Anesthesia for laparoscopy. Author(s): Keith L, Silver A, Becker M. Source: J Reprod Med. 1974 June; 12(6): 227-33. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4275894

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Antioxidants and cancers of the esophagus and gastric cardia. Author(s): Terry P, Lagergren J, Ye W, Nyren O, Wolk A.

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Source: International Journal of Cancer. Journal International Du Cancer. 2000 September 1; 87(5): 750-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10925371 •

Behavioral approaches to the treatment of gastrointestinal motility disorders. Author(s): Whitehead WE, Schuster MM. Source: The Medical Clinics of North America. 1981 November; 65(6): 1397-411. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7329154

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Beyond acid suppressants in gastro-oesophageal reflux disease. Author(s): Fitzgerald RC. Source: Gut. 2001 September; 49(3): 320-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511549

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Biofeedback and self-regulation in the treatment of diffuse esophageal spasm: a single-case study. Author(s): Latimer PR. Source: Biofeedback Self Regul. 1981 June; 6(2): 181-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7260187

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Biofeedback improvement of lower esophageal sphincter pressures and reflux symptoms. Author(s): Gordon A, Gordon E, Berelowitz M, Bremner CH, Bremner CG. Source: Journal of Clinical Gastroenterology. 1983 June; 5(3): 235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6863880

•

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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Gastroesophageal reflux disease update for the primary care physician. Author(s): Mitz HS. Source: J Am Osteopath Assoc. 1999 August; 99(8 Suppl): S1-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10732396

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Improvement of gastroesophageal reflux disease after initiation of a lowcarbohydrate diet: five brief case reports. Author(s): Yancy WS Jr, Provenzale D, Westman EC.

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Source: Alternative Therapies in Health and Medicine. 2001 November-December; 7(6): 120, 116-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712463 •

Neurobiology of relaxation training in gastroesophageal reflux disease. Author(s): Friedman EH. Source: Gastroenterology. 1995 February; 108(2): 619-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7835614

•

Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux disease. Author(s): McDonald-Haile J, Bradley LA, Bailey MA, Schan CA, Richter JE. Source: Gastroenterology. 1994 July; 107(1): 61-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8020690

•

Rumination, heartburn, and daytime gastroesophageal reflux. A case study with mechanisms defined and successfully treated with biofeedback therapy. Author(s): Shay SS, Johnson LF, Wong RK, Curtis DJ, Rosenthal R, Lamott JR, Owensby LC. Source: Journal of Clinical Gastroenterology. 1986 April; 8(2): 115-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3462241

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Successful drug-specific chronotherapy with the H2 blocker famotidine in the symptomatic relief of gastroesophageal reflux disease. Author(s): Humphries TJ, Root JK, Hufnagel K. Source: Annals of the New York Academy of Sciences. 1991; 618: 517. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2006804

•

Usage of supplemental alternative medicine by community-based patients with gastroesophageal reflux disease (GERD). Author(s): Hayden CW, Bernstein CN, Hall RA, Vakil N, Garewal HS, Fass R. Source: Digestive Diseases and Sciences. 2002 January; 47(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11837707

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/

Alternative Medicine 101

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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

•

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 gastroesophageal reflux disease; 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 Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Chronic Candidiasis Source: Healthnotes, Inc.; www.healthnotes.com Colic Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Dysphagia Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc.; www.healthnotes.com

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Gastritis Source: Integrative Medicine Communications; www.drkoop.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 High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Irritable Bowel Syndrome Alternative names: Spastic Colon Source: Prima Communications, Inc.www.personalhealthzone.com Leukoplakia Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Sinus Infection Source: Integrative Medicine Communications; www.drkoop.com Sinusitis Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 103

Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Ayurveda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,672,00.html Osteopathy Source: Integrative Medicine Communications; www.drkoop.com Osteopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724,00.html Testing for Stomach Acidity Source: Healthnotes, Inc.; www.healthnotes.com

•

Herbs and Supplements 5-HTP Source: Integrative Medicine Communications; www.drkoop.com 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc.; www.healthnotes.com Aloe Vera Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Aluminum Hydroxide Source: Healthnotes, Inc.; www.healthnotes.com Andrographis Alternative names: Andrographis paniculata Source: Healthnotes, Inc.; www.healthnotes.com Angkak Source: Integrative Medicine Communications; www.drkoop.com

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Baking Soda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,835,00.html Beni-Koji Source: Integrative Medicine Communications; www.drkoop.com Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com Blessed Thistle Alternative names: Cnicus benedictus Source: Healthnotes, Inc.; www.healthnotes.com Boldo Alternative names: Peumus boldus Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Cayenne Alternative names: Capsicum annuum, Capsicum frutescens Source: Healthnotes, Inc.; www.healthnotes.com Chamaemelum Nobile Source: Integrative Medicine Communications; www.drkoop.com Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com Chamomile Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,766,00.html Chaparral Alternative names: Larrea tridentata Source: Healthnotes, Inc.; www.healthnotes.com Cimetidine Source: Healthnotes, Inc.; www.healthnotes.com Cisapride Source: Healthnotes, Inc.; www.healthnotes.com

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Dandelion Alternative names: Taraxacum officinale Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10021,00.html Devil’s Claw Alternative names: Harpagophytum procumbens Source: Healthnotes, Inc.; www.healthnotes.com Devil's Claw Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,970,00.html Digestive Enzymes Source: Healthnotes, Inc.; www.healthnotes.com Digestive Enzymes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10051,00.html Famotidine Source: Healthnotes, Inc.; www.healthnotes.com Fennel Alternative names: Foeniculum vulgare Source: Healthnotes, Inc.; www.healthnotes.com Gamma-Oryzanol Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10028,00.html Gentian Alternative names: Gentiana lutea Source: Healthnotes, Inc.; www.healthnotes.com Gentian Source: Prima Communications, Inc.www.personalhealthzone.com German Chamomile Alternative names: Matricaria recutita Source: Integrative Medicine Communications; www.drkoop.com Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc.; www.healthnotes.com

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Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.drkoop.com Ginger Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,787,00.html Glucosamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,790,00.html Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hong Qu Source: Integrative Medicine Communications; www.drkoop.com Hung-Chu Source: Integrative Medicine Communications; www.drkoop.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Lactase Source: Healthnotes, Inc.; www.healthnotes.com Lansoprazole Source: Healthnotes, Inc.; www.healthnotes.com Lavender Alternative names: Lavandula officinalis Source: Healthnotes, Inc.; www.healthnotes.com Lemon Balm Alternative names: Melissa officinalis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lobelia Alternative names: Lobelia inflata Source: Healthnotes, Inc.; www.healthnotes.com Marshmallow Alternative names: Althea officinalis Source: Healthnotes, Inc.; www.healthnotes.com Marshmallow Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10042,00.html Matricaria Recutita Source: Integrative Medicine Communications; www.drkoop.com Meadowsweet Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Mentha X Piperita Source: Integrative Medicine Communications; www.drkoop.com Metoclopramide Source: Healthnotes, Inc.; www.healthnotes.com Monascus Source: Integrative Medicine Communications; www.drkoop.com Nizatidine Source: Healthnotes, Inc.; www.healthnotes.com Omeprazole Source: Healthnotes, Inc.; www.healthnotes.com Peppermint Alternative names: Mentha piperita Source: Healthnotes, Inc.; www.healthnotes.com Peppermint Alternative names: Mentha x piperita Source: Integrative Medicine Communications; www.drkoop.com Peppermint Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,812,00.html

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Phenylalanine Source: Healthnotes, Inc.; www.healthnotes.com Ranitidine Source: Healthnotes, Inc.; www.healthnotes.com Red Koji Source: Integrative Medicine Communications; www.drkoop.com Red Leaven Source: Integrative Medicine Communications; www.drkoop.com Red Rice Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Alternative names: Monascus purpureus Source: Healthnotes, Inc.; www.healthnotes.com Red Yeast Rice Alternative names: Angkak, Beni-koju, Hong Qu, Hung-chu, Monascus, Red Leaven, Red Rice, Red Koji, Zhitai, Xue Zhi Kang Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Source: Prima Communications, Inc.www.personalhealthzone.com Red Yeast Rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10054,00.html Roman Chamomile Alternative names: Chamaemelum nobile Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Slippery Elm Alternative names: Ulmus rubra, Ulmus fulva Source: Healthnotes, Inc.; www.healthnotes.com Slippery Elm Source: Prima Communications, Inc.www.personalhealthzone.com Slippery Elm Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10056,00.html

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Wormwood Alternative names: Artemisia absinthium Source: Healthnotes, Inc.; www.healthnotes.com Yarrow Alternative names: Achillea millefolium Source: Healthnotes, Inc.; www.healthnotes.com Zhitai Source: Integrative Medicine Communications; www.drkoop.com Zingiber Officinale Source: Integrative Medicine Communications; www.drkoop.com Zue Zhi Kang Source: Integrative Medicine Communications; www.drkoop.com

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

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CHAPTER 4. PATENTS ON GASTROESOPHAGEAL REFLUX DISEASE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “gastroesophageal reflux disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on gastroesophageal reflux disease, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Gastroesophageal Reflux Disease By performing a patent search focusing on gastroesophageal reflux disease, 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 8Adapted

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

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

Device and method for treatment of gastroesophageal reflux disease Inventor(s): Ganz; Robert A. (1431 Lakeview, Minneapolis, MN 55416), Zelickson; Brian D. (2764 Drew Ave. South, Minneapolis, MN 55416) Assignee(s): none reported Patent Number: 6,073,052 Date filed: November 15, 1996 Abstract: A lower esophageal sphincter tightening device for treating gastroesophageal reflux disease which includes an insertion device, an energy source, and an energy transmitting device. The insertion device, by insertion through a body opening, positions the energy transmitting device in the proximity of the lower esophageal sphincter. The energy source generates and transmits energy via the insertion device to the energy transmitting device which directs the transmitted energy onto the lower esophageal sphincter which is comprised largely of collagen. The energy source transmits energy at a level sufficient to cause heating of the sphincter's collagen resulting in a shrinkage of the collagen and a tightening of the sphincter. Excerpt(s): The invention pertains to the treatment of gastroesophageal reflux disease (GERD). The gastric contents are normally prevented from entering the esophagus by a lower esophageal sphincter (LES) mechanism. The LES is a physiologic, non-anatomic area involving the lower 3 centimeters of the esophagus and like other smooth muscle sphincters in the body, anal or urinary, it is tonically contracted to prevent reflux. A healthy LES opens for a brief period of several seconds in response to swallowing to allow the passage of food. It then quickly regains its tone when the food has passed. Treatment of a weakened or inappropriately relaxing sphincter can be either medical or surgical. Known medical treatments include measures or medications that attempt to decrease acid secretion, increase gastric emptying or strengthen the LES. However, the medications are expensive and the measures typically have to be continued on a life long basis. Web site: http://www.delphion.com/details?pn=US06073052__

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Heartburn and reflux disease treatment with controlled wireless energy supply Inventor(s): Forsell; Peter (Menzingen, CH) Assignee(s): Obtech Medical AG (Baar, CH) Patent Number: 6,450,173 Date filed: February 10, 2000 Abstract: A heartburn and reflux disease treatment apparatus and method includes and uses an operable restriction device implanted in a patient and engaging the stomach close to the cardia or engaging the esophagus to form a restricted passageway in the stomach or esophagus. A source of energy external to the patient's body and a control device for releasing wireless energy from the source of energy from outside the patient's

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body are provided, so that the released wireless energy is used in connection with the operation of the restriction device to enlarge or contract the passageway. Excerpt(s): The present invention relates to a heartburn and reflux disease treatment apparatus and method. More specifically, the invention relates to a heartburn and reflux disease treatment apparatus and method for surgical application in the abdomen of a patient for forming a restricted food passageway in the esophagus or stomach. The term "patient" includes an animal or a human being. Chronic heartburn and reflux disease is a widespread medical problem. This is often due to hiatal hernia, i.e. a portion of the stomach immediately below the gastric fundus slides upwardly through the esophageal hiatus. In consequence, stomach acids and foods are regurgitated into the esophagus. In the late 1970s a prior art prosthesis called Angelchik, according to U.S. Pat. No. 3,875,928, was used to operatively treat heartburn and reflux disease. However, the Angelchik prosthesis had a major disadvantage in that it was not possible to adjust the size of the restriction opening after the operation. A further disadvantage was that the prosthesis did not satisfactorily protect the esophagus and the surrounding area against injuries due to poor shape of the prosthesis. Therefore, operations using the Angelchik prosthesis are no longer practiced. Web site: http://www.delphion.com/details?pn=US06450173__ •

Heartburn treatment Inventor(s): Berlin; Roger (Haverford, PA), Simon; Thomas (Berwyn, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,667,794 Date filed: September 11, 1996 Abstract: A method for treating a patient suffering from heartburn and having no substantial esophageal erosion, comprising administering to the patient a composition comprising an amount of famotidine between about 5 mg and 10 mg. In one embodiment, the amount of famotidine is about 5 mg. In another embodiment, the amount of famotidine is about 10 mg.A method for treating a patient suffering from heartburn and having no substantial esophageal erosion, comprising administering to the patient a composition comprising an amount of famotidine between about 5 mg and 10 mg, and an antacid. In one embodiment, the amount of famotidine is about 5 mg. In another embodiment, the amount of famotidine is about 10 mg. Excerpt(s): Heartburn, or pyrosis, is a sensation of pain or burning located substernally or high in the epigastrium with radiation into the neck and occasionally to the arms, associated with regurgitation of acid-peptic gastric juice into the esophagus. Occassional heartburn is common in normal persons, but frequent and severe heartburn is generally a manifestation of esophageal dysfunction. Heartburn may result from abnormal motor activity or distention of the esophagus relfux of acid or bile into the esophagus, or direct esophageal mucosa irritation (esophagitis). Heartburn is most often associated with gastroesophageal reflux. In this setting, heartburn typically occurs after a meal, with stooping or bending, or when the patient is supine. It may be accompanied by the spontaneous appearance in the mouth of fluid which may be salty, sour, or bitter and green or yellow. Heartburn may arise following the ingestion of certain foods (e.g. citrus fruit juices) or drugs (e.g. alcohol or aspirin). Characteristically, heartburn is alleviated promptly, even if only temporarily, by antacids. Heartburn may also occur in the absence of a demonstrated anatomic or physiologic condition. In this setting, it is

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frequently accompanied by aerophagia, which may represent an attempt by the patient to relieve discomfort, and is often attributed to psychological factors for lack of other explanations. Web site: http://www.delphion.com/details?pn=US05667794__ •

Implantable esophageal sphincter apparatus for gastroesophageal reflux disease and method Inventor(s): Meah; Nizam N. (236 Plum Cir., Lake Jackson, TX 77566) Assignee(s): none reported Patent Number: 6,432,040 Date filed: September 14, 2000 Abstract: An implantable esophageal sphincter apparatus with an adjustable band to be placed at the lower part of the esophagus. The inflation of the band, or sphincter body, can be increased or decreased to adjust the tightness of the device. The inflatable sphincter body may be wrapped around the esophagus and may be connected to an inflation device with a fluid reservoir. The inflation device may have a pump mechanism that will respond to external control to increase or decrease the inflation of the sphincter body. The sphincter apparatus will be held in place at the area of implantation by sutures and by fenestration mechanisms, which will allow ingrowths of tissue or fibrous elements of the body around the sphincter apparatus or into porous materials on the sphincter apparatus. The apparatus may also include a circumferential shield on a distal side of the sphincter apparatus. The shield is adapted to fit against the distal or lower side of the patient's diaphragm and inhibits the development of a hiatus hernia, that is, a protrusion of the stomach past the diaphragm through the passage for the esophagus. Excerpt(s): The present invention relates to an implantable apparatus for use treating gastroesophageal acid reflux and particularly to an artificial sphincter for the lower esophageal sphincter. Gastroesophageal reflux disease (GERD) is one of the most common medical illnesses in today's western society. Gastroesophageal reflux occurs when the contents of the stomach, including acids and digestive fluids, leak back past the lower esophageal sphincter into the esophagus. This produces the sensation commonly referred to as "heartburn". Over prolonged periods, this condition can seriously compromise a person's health. Studies indicate that the incidence of gastroesophageal reflux is on the rise. For example, health care providers use Common Procedural Terminology ("CPT") codes to report treatment of certain conditions. In 1999, the CPT code for GERD was the most commonly used code from gastroenterologists' offices in the United States, indicating the prevalence of the condition. Incidence of this disease is similarly common in all parts of Europe and probably in any affluent society. Currently, there are four options available for treatment of gastroesophageal reflux disease. These options are life-style modification, medication, surgery, and endoscopic fundoplication. Life-style modification comprises dietary changes and positioning of body so that, with the help of gravity, upward reflux of food and acid from the stomach is prevented. This treatment is seldom effective alone. Web site: http://www.delphion.com/details?pn=US06432040__

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Implantable particles for urinary incontinence Inventor(s): Boschetti; Egisto (Croissy sur Seine, FR), Thomas; Richard (Elmont, MA), Vogel; Jean Marie (Boxborough, MA) Assignee(s): Biosphere Medical, Inc. (Rockland, MA) Patent Number: 6,335,028 Date filed: March 5, 1999 Abstract: The invention encompasses the treatment of urinary incontinence, gastroesophageal reflux disease and the amelioration of skin wrinkles using biocompatible hydrophilic cationic microparticles and a cell adhesion promoter. Excerpt(s): The present invention relates to tissue bulking, the treatment gastroesophageal reflux disease, urinary incontinence and the amelioration of skin wrinkles. Although gastroesophageal reflux is a normal physiological phenomenon, in some cases it is a pathophysiological situation that can result in a variety of symptoms which may become severe in extreme cases. Gastro-Esophageal Reflux Disease ("GERD"), describes a backflow of acidic and enzymatic liquid from the stomach to the esophagus. It causes burning sensations behind the sternum that may be accompanied by regurgitation of gastric acid into the mouth or even the lung. Complications of GERD which define the severity of the disease include esophageal tissue erosion, and esophageal ulcer wherein normal epithelium is replaced by a pathological tissue. Statistical data indicate that about 35% of the American population suffer from heartburn at least once a month and between 5 to 10% once a day. More importantly for this kind of disease about 2% of the American population suffer from GERD based on medical evidence data from endoscopic examination. This disease is related to the age of individuals and seems to increase after 40 years of age. (Nebel O. T. et al., Am. J. Dig. Dis., 21(11):953-956 (1976)). Web site: http://www.delphion.com/details?pn=US06335028__

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Method and apparatus for detection of acid reflux Inventor(s): Baylor; Richard A. (Champaign, IL) Assignee(s): Baymar, Inc. (Champaign, IL) Patent Number: 6,475,145 Date filed: May 17, 2000 Abstract: Methods and apparatus for monitoring gastrointestinal pH levels are disclosed. A gastroesophageal diagnostic device for determining the duration of exposure of a patient's esophagus to pH levels clinically significant for gastroesophageal reflux disease is disclosed. Excerpt(s): It has been estimated by the U.S. Department of Health and Human Services that about seven million people in the United States suffer from GERD. The incidence of GERD increases after the age of 40, and more than 50 percent of those afflicted with GERD are between the ages of 45-64. (Statistics from Digestive Diseases in the United States: Epidemiology and Impact, National Digestive Diseases Data Working Group, James E. Everhart, MD, MPH, Editor, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, NIH Publication No. 94-1447, May 1994.) For general information about GERD see the following: Fennerty, M. B., Sampliner, R. E., Gastroesophageal reflux disease, Hospital Medicine, 29(4): 28-40

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(1993); and Orlando, R. C., Reflux esophagitis, in Textbook of Gastroenterology, 1: 11231147, Yamada, T., ed., J. B. Lippincott Co., Philadelphia, Pa. (1991). In the lower part of esophagus, where the esophagus meets the stomach, there is a muscular valve called the lower esophageal sphincter (LES). Normally, the LES relaxes to allow food to enter into the stomach from the esophagus. The LES then contracts to prevent stomach acids from entering the esophagus. In GERD, the LES relaxes too frequently or at inappropriate times allowing stomach acids to reflux into the esophagus. The most common symptom of GERD is heartburn. Acid reflux also leads to esophageal inflammation, which causes symptoms such as odynophagia, or painful swallowing, and dysphagia, or difficulty swallowing. Pulmonary symptoms such as coughing, wheezing, asthma, or inflammation of the vocal cords or throat may occur in some patients. More serious complications from GERD include esophageal ulcers and esophageal stricture, or narrowing of the esophagus. The most serious complication from chronic GERD is a condition called Barrett's esophagus in which the epithelium of the esophagus is replaced with abnormal tissue. Barrett's esophagus is a risk factor for the development of cancer of the esophagus. Web site: http://www.delphion.com/details?pn=US06475145__ •

Method for preventing heartburn Inventor(s): Berlin; Roger (Haverford, PA), Gates; Thomas N. (Bonita Springs, FL), Simon; Thomas (Berwyn, PA) Assignee(s): Mc Neil-PPC, Inc. (Skillman, NJ), Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,854,267 Date filed: June 2, 1995 Abstract: A method for preventing heartburn episodes in a patient susceptible to suffering heartburn episodes following ingestion of heartburn-inducing food or beverage, comprising administering to the patient, 30 minutes prior to consumption by the patient of the food or beverage, a composition comprising an amount of famotidine of 10 mg. Excerpt(s): Heartburn, or pyrosis, is a sensation of pain or burning located substernally or high in the epigastrium with radiation into the neck and occasionally to the arms, associated with regurgitation of acid-peptic gastric juice into the esophagus. Occasional heartburn is common in normal persons, but frequent and severe heartburn is generally a manifestation of esophageal dysfunction. Heartburn may result from abnormal motor activity or distention of the esophagus reflux of acid or bile into the esophagus, or direct esophageal mucosa irritation (esophagitis). Heartburn is most often associated with gastroesophageal reflux. In this setting, heartburn typically occurs after a meal, with stooping or bending, or when the patient is supine. It may be accompanied by the spontaneous appearance in the mouth of fluid which may be salty, sour, or bitter and green or yellow. Heartburn may arise following the ingestion of certain foods (e.g. citrus fruit juices) or drugs (e.g. alcohol or aspirin). Reflux esophagitis consists of esophageal mucosal damage resulting from reflux of gastric or intestinal contents into the esophagus. Esophagitis, an inflammation of the esophagus from regurgitation of acid gastric contents, producing substernal pain, develops when the mucosal defenses that normally counteract the effect of injurious agents on the esophageal mucosa succumb to the onslaught of the refluxed acid pepsin or bile. Mild esophagitis shows microscopic changes of mucosal infiltration with granulocytes or eosinophils, hyperplasia of basal cells, and elongation of dermal pegs. Erosive esophagitis shows endoscopically visible

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damage to the mucosa in the form of marked redness, friability, bleeding, superficial linear ulcers, and exudates. Web site: http://www.delphion.com/details?pn=US05854267__ •

Method for testing for gastroesophageal reflux disease Inventor(s): Orr; William C. (5300 N. Independence Ave., Suite 130, Oklahoma City, OK 73112) Assignee(s): none reported Patent Number: 5,951,468 Date filed: August 20, 1997 Abstract: An easy, safe and inexpensive procedure to testing the presence of esophageal acid sensitivity in a patient involves having the patient swallow a controlled quantity of a weak acid solution and a similar-tasting controlled quantity of a neutral solution and recording the reactions or symptoms experienced by the patient during the drinking of each solution. The acid solution only should affect the sensitivity of the esophageal lining in patients with esophageal acid sensitivity, providing heartburn and other related symptoms to include non-cardiac chest pain, but should not have any significant effect on patients without esophageal acid sensitivity. The neutral solution may be altered to simulate the taste of the acid solution and reduce the effect the taste of the solutions may have on the test results. Excerpt(s): This invention relates to medical diagnostic testing, and more particularly to a medical test that determines the likelihood that chest pain symptoms can be attributed to the reflux of acidic gastric contents. Gastroesophageal reflux is a common human condition arising from the backwash or "reflux" of stomach acid into the esophagus. Mild reflux with "heartburn" is a very common condition experienced by nearly everyone at one time or another. However, prolonged or repeated bathing of the esophagus with gastric acid may lead to gastroesophageal reflux disease or "GERD." GERD is a disease that produces symptoms and/or tissue damage secondary to the reflux of gastric contents into the esophagus. A primary symptom of GERD is heartburn. The prevalence of GERD in the U.S. population is increasing and, at a minimum, effects approximately ten percent (10%) of the U.S. population. This segment of the population has heartburn daily. More than one-third of the U.S. population, however, is estimated to have intermittent heartburn symptoms. Left untreated, GERD may lead to esophagitis, an esophageal ulceration, stricture or a malignant tumor formation. Web site: http://www.delphion.com/details?pn=US05951468__

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Method for treating gastroesophageal reflux disease and apparatus for use therewith Inventor(s): Silverman; David E. (Palo Alto, CA), Stein; Alan (Moss Beach, CA) Assignee(s): Enteric Medical Technologies, Inc. (Palo Alto, CA) Patent Number: 6,238,335 Date filed: January 15, 1999 Abstract: A method for treating gastroesophageal reflux disease in a body of a mammal is provided. At least one nonaqueous solution is introduced into the wall in the vicinity

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of the lower esophageal sphincter. A nonbiodegradable solid is formed from the at least one nonaqueous solution in the wall to augment the wall. An apparatus for use in the procedure is provided. Excerpt(s): This invention pertains to the treatment of gastroesophageal reflux disease and, more particularly, to the treatment of gastroesophageal reflux disease by augmenting tissue in the upper gastrointestinal tract. Gastroesophageal reflux disease (GERD) is a failure of the anti-reflux barrier, allowing abnormal reflux of gastric contents into the esophagus. Gastroesophageal reflux disease is a disorder which is usually characterized by a defective lower esophageal sphincter (LES), a gastric emptying disorder with or without failed esophageal peristalsis. The disease usually manifests itself during "transient lower esophageal sphincter relaxation" episodes, the frequency of which is greatly increased in patients who reflux. Medical or drug therapy is the first line of management for gastroesophageal refluxes. However, drug management does not address the condition's mechanical etiology. Thus symptoms recur in a significant number of sufferers within one year of drug withdrawal. In addition, while medical therapy may effectively treat the acid-induced symptoms of gastroesophageal reflux disease, esophageal mucosal injury may continue due to ongoing alkaline reflux. Since gastroesophageal reflux disease is a chronic condition, medical therapy involving acid suppression and/or promotility agents may be required for the rest of a patient's life. The expense and psychological burden of a lifetime of medication dependence, undesirable life style changes, uncertainty as to the long term effects of some newer medications and the potential for persistent mucosal changes despite symptomatic control, all make surgical treatment of gastroesophageal reflux disease an attractive option. Unfortunately, surgical intervention is a major operation with all attendant morbidities, mortality and risk of failure requiring further surgery in the case of over-correction. Laparoscopic surgery requires a very high level of skill and special training for it to be successful. Web site: http://www.delphion.com/details?pn=US06238335__ •

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

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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 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__ •

Methods and pharmaceutical compositions for treating episodic heartburn Inventor(s): Wolfe; M. Michael (Newton, MA) Assignee(s): Brigham and Women's Hospital, Inc. (Boston, MA) Patent Number: 5,229,137 Date filed: May 6, 1992 Abstract: Pharmaceutical medications and methods are disclosed for providing instant and sustained relief from pain or symptoms associated with episodic heartburn in humans. The medications consist essentially of antacids and histamine H.sub.2 -receptor antagonists, and may be administered on an as-needed basis in liquid or solid dosage forms. Typical antacids which may be used in combination with the histamine H.sub.2 receptor antagonist are conventional antacids which are well known and widely used in the treatment of excess acid related gastrointestinal dysfunctions. Exemplary of typical antacids include, sodium bicarbonate, calcium carbonate, magnesium hydroxide and aluminum hydroxide, as well as commercially available high potency, flavored antacids. Histamine H.sub.2 -receptor antagonists which may be used in combination include those conventionally used in the treatment of peptic ulcers, such as, for example, cimetidine, ranitidine, famotidine and nizatidine. In carrying out the methods, an antacid and histamine H.sub.2 -receptor antagonist may be administered together as a single unitary dose in the form of a liquid or solid, or administered together, but separately as either liquids or solids or a combination thereof. The oral medications when formulated as a single unitary dose may include other additives, such as, for example, antiflatulents, flavorings, sweeteners and the like. Excerpt(s): The present invention relates to pharmaceutical compositions and methods for providing immediate and sustained relief from pain, discomfort and/or symptoms associated with episodic heartburn in humans. About 7-10 percent of all people suffer

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daily, and about 25-40 percent monthly, from pain, discomfort and/or symptoms associated with episodic heartburn. Episodic heartburn is defined as the sensation of burning under the sternum (breastbone) and is usually associated with the ingestion of different foods. Episodic heartburn has also been referred to as "sour stomach," "indigestion," and "waterbrash/regurgitation." Although different foods, such as coffee, mints, fatty foods, alcohol, and chocolate, are usually implicated in the etiology of episodic heartburn, these symptoms can be caused by any type of food in certain people. Moreover, in many people, there is no inciting agent that can be identified, rather the disorder occurs without any known provocation. At present, the primary treatment is based upon the neutralization of gastric acid and pepsin with antacids, such as, for example, aluminum hydroxides, calcium carbonates, magnesium hydroxides and sodium bicarbonates. Of less importance, treatment is based upon the inhibition of secretion by histamine H.sub.2 -receptor antagonists, such as cimetidine and ranitidine. Web site: http://www.delphion.com/details?pn=US05229137__ •

Non-invasive treatment of gastroesophageal reflux disease Inventor(s): Blewett; Jeffrey J. (Plantsville, CT), Bolanos; Henry (East Norwalk, CT), Van Leeuwen; Timothy O. (Bloomfield, CT) Assignee(s): United States Surgical Corporation (Norwalk, CT) Patent Number: 5,571,116 Date filed: October 2, 1994 Abstract: Instrumentation for transoral treatment of gastroesophageal reflux disease (GERD) are disclosed. In a preferred embodiment, an instrument includes a remotely operable invagination device for atraumatically approximating the lower esophagus and fundus of the stomach and for invaginating the gastroesophageal junction into the stomach thereby involuting the surrounding fundic wall. The same or a separate instrument includes a remotely operable surgical fastening instrument for fastening together the invaginated lower esophagus and fundic wall. A method of surgically treating GERD is also disclosed. Excerpt(s): The invention relates to instruments for surgical correction of gastroesophageal reflux disease (GERD) and, more particularly, to surgical instrumentation and methods for performing non-invasive treatment of gastroesophageal reflux disease. Gastroesophageal reflux disease (GERD) is a common gastroesophageal disorder in which stomach contents leak into the lower esophagus due to a dysfunction of the lower esophageal sphincter. As a result, patients suffer numerous symptoms including heartburn, pulmonary disorders, and chest pain. Chronic GERD subjects the esophagus to ulcer formation, esophagitis, and numerous other complications. Advances in drug therapy for GERD include histamine receptor blockers (PEPCID.TM., ZANTAC.TM., etc.) which reduce stomach acid secretion and OMEPRAZOLE.TM. which may completely shut off stomach acid (achlorhydria). Although drugs may provide short term relief, drugs do not address the underlying problem of lower esophageal sphincter dysfunction. Invasive procedures requiring percutaneous introduction of instrumentation to the operative site exist for the surgical correction of GERD. One such procedure, Nissen fundoplication, involves constructing a new "valve" to support the lower esophageal sphincter by wrapping the gastric fundus around the lower esophagus. Although the operation has a high rate of success. It is a major surgical procedure having the usual risks of abdominal surgery along with the intraoperative risk of perforation of the esophagus or of the cardia.

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Web site: http://www.delphion.com/details?pn=US05571116__ •

Prosthetic gastroesophageal valve Inventor(s): Kelleher; Brian S. (San Diego, CA), Kilcoyne; John (San Diego, CA) Assignee(s): Endonetics, Inc. (San Diego, CA) Patent Number: 6,264,700 Date filed: August 27, 1998 Abstract: Disclosed is a prosthetic gastroesophageal valve assembly, for transesophageal implantation to treat gastroesophageal reflux disease. The valve assembly includes an anchor for attachment to the wall of the esophagus and a valve permanently or removably connected to the anchor. Related devices and methods are also disclosed. Excerpt(s): This invention relates to a prosthetic valve for non-invasive insertion in the vicinity of the lower esophagus sphincter (LES). Gastroesophageal reflux is a physical condition in which stomach acids reflux, or flow back up from the stomach into the esophagus. Frequent reflux episodes (two or more times per week), results in a more severe problem known as gastroesophageal reflux disease (GERD). Gastroesophageal reflux disease is the most common form of dyspepsia, being present in approximately 40% of adults in the United States or an intermittent basis and some 10% on a daily basis. Dyspepsia or heartburn, is defined as a burning sensation or discomfort behind the breastbone or sternum and is the most common symptom of GERD. Other symptoms of gastroesophageal reflux disease include dysphasia, odynophagia, hemorrhage, water brash, and pulmonary manifestations such as asthma, coughing or intermittent wheezing due to acid aspiration. Dyspepsia also may mimic the symptoms of a myocardial infarction or severe angina pectoris. Factors that are believed to cause GERD include: transient lower esophageal sphincter relaxations, decreased LES resting tone, delayed stomach emptying, and ineffective esophageal clearance. One primary cause of gastroesophageal reflux disease is the lack of competency of the lower esophageal sphincter. The lower esophageal sphincter or valve, is comprised of both smooth and skeletal muscle located at the gastroesophageal (GE) junction. Web site: http://www.delphion.com/details?pn=US06264700__

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Submucosal esophageal bulking device Inventor(s): Johnson; George M. (Santa Ana, CA), Tsukashima; Ross (San Diego, CA), Yurek; Matthew Thomas (San Diego, CA) Assignee(s): Endonetics, Inc. (San Diego, CA) Patent Number: 6,401,718 Date filed: August 30, 2000 Abstract: Disclosed is an esophageal bulking device for implantation below the mucosa in the vicinity of the lower esophageal sphincter. Preferably, the bulking device comprises an expandable hydrogel implant. Also disclosed are methods of treating gastroesophageal reflux disease, by implanting an expandable bulking device below the mucosa in the vicinity of the lower esophageal sphincter. The bulking device may be subsequently explanted from the vicinity of the lower esophageal sphincter.

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Excerpt(s): The present invention relates generally to the field of esophageal prosthetics. More specifically, a prosthesis delivery device is disclosed for submucosal insertion of a prosthetic bulking device. Gastroesophageal reflux is a physical condition in which stomach acids reflux, or flow back from the stomach into the esophagus. Frequent reflux episodes (two or more times per week), may result in a more severe problem known as gastroesophageal reflux disease (GERD). Gastroesophageal reflux disease is the most common form of dyspepsia, being present in approximately 40% of adults in the United States on an intermittent basis and some 10% on a daily basis. Dyspepsia, or heartburn, is defined as a burning sensation or discomfort behind the breastbone or sternum and is the most common symptom of GERD. Other symptoms of GERD include dysphasia, odynophagia, hemorrhage, water brash, and pulmonary manifestations such as asthma, coughing or intermittent wheezing due to acid aspiration. Dyspepsia may also mimic the symptoms of a myocardial infarction or severe angina pectoris. Many factors are believed to contribute to the onset of GERD including transient lower esophageal sphincter relaxations, decreased LES resting tone, delayed stomach emptying, and an ineffective esophageal clearance. Many in the field agree, however, that the primary cause of GERD is the lack of competency of the lower esophageal sphincter. Web site: http://www.delphion.com/details?pn=US06401718__ •

Sutureless gastroesophageal anti-reflux valve prosthesis and tool for peroral implantation thereof Inventor(s): Taylor; Thomas V. (1806 Vassar, Houston, TX 77098) Assignee(s): none reported Patent Number: 6,544,291 Date filed: March 26, 2001 Abstract: Disclosed are an instrument, valve prosthesis and procedure for the minimally invasive implantation of a sutureless anti-reflux valve in a patient for the treatment of gastroesophageal reflux disease. A prosthesis is provided that comprises a cylindrical housing, a mounting ring and a one-way anti-reflux valve depending from the mounting ring. The cylindrical housing is constructed of a memory material that can be fixed in the gastroesophageal junction. The mounting ring and the anti-reflux valve are fixed within the housing. Excerpt(s): This invention relates to a device and non-invasive surgical method for treating gastroesophageal reflux disease. More specifically, it relates to an anti-reflux valve prosthesis and associated instrumentation for its peroral placement and in situ fixing at the gastroesophageal junction, to prevent the reflux of gastric contents into the esophagus in the treatment of gastroesophageal reflux disease in a patient. Gastroesophageal reflux disease (GERD) is the commonest cause of dyspepsia, affecting some 30% of the United States adult population intermittently and some 10% on a continuous and troublesome basis. Gastroesophageal reflux disease produces heartburn, abdominal pain and regurgitation of acid-containing gastric contents into the esophagus and pharynx. It may also lead to alteration of the lining of the esophagus (Barrett's Esophagus), which may go on to produce esophageal cancer. Current methods of treating GERD include powerful antacid medication therapies and surgical interventions. Medication therapy with powerful antacids is directed at treating the symptoms of GERD, and is necessarily not curative. Furthermore, medication-based therapies are not always fully effective, as reflux is not prevented and the esophagus may continue to be exposed to gastric content.

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Web site: http://www.delphion.com/details?pn=US06544291__ •

Therapy pillow useful for treating gastroesophageal reflux disease (gerd) and other applications Inventor(s): Colavito; Barbara J. (Durham, NC), Muntendam; Pieter (Raleigh, NC) Assignee(s): Glaxo Wellcome Inc. (Research Triangle Park, NC) Patent Number: 5,697,112 Date filed: November 8, 1996 Abstract: A therapy pillow comprising a wedge-shaped resilient foam element having a planar recess in the medial portion of the top surface thereof. A flexible plastic container adapted to be sealingly filled with a fluid snugly fits into the planar recess of the foam element so as to be substantially coplanar with the top surface thereof when filled with a suitable fluid such as water. Excerpt(s): The present invention relates to supportive pillows, and more particularly relates to a therapy pillow useful for treating symptoms of gastroesophageal reflux disease (GERD) and for other applications. Gastroesophageal reflux disease (GERD) is a well known problem encountered by physicians in most medical specialties. The disease encompasses a broad range of clinical presentations, with no consistent relationship between subjective complaints and objective findings. Some degree of gastroesophageal reflux occurs in normal people, and should be considered a benign physiologic process. The term gastroesophageal reflux disease (GERD) is best defined as including symptoms and/or evidence of tissue damage secondary to reflux of gastric contents. The varied manifestations of gastroesophageal reflux disease (GERD) may obscure its underlying cause and make it very difficult to diagnose and treat. Chronic reflux has been implicated in the cause of non-cardiac chest pain as well as disorders of the pharynx, larynx and respiratory tract. About half of adult asthmatics may also have gastroesophageal reflux disease (GERD) that tends to contribute to their asthma. Also, gastroesophageal reflux disease (GERD) is probably involved in a variety of well known pulmonary diseases. Web site: http://www.delphion.com/details?pn=US05697112__

Patent Applications on Gastroesophageal Reflux Disease As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to gastroesophageal reflux disease:

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

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Endoscopic fundoplication devices and methods for treatment of gastroesophageal reflux disease Inventor(s): Grigoryants, Sergey S.; (Arlington, MA), Vu, Liem T.; (Needham, MA) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030236536 Date filed: June 20, 2002 Abstract: Endoscopic devices and methods used for fastening multiple tissue layers, such as, for example, an endoscopic fundoplication procedure, are disclosed. The endoluminal device includes a tissue fastener, a flexible needle having means for grasping and releasing a portion of the tissue fastener, and a deflector for deflecting and guiding the needle toward the multiple tissue layers. Excerpt(s): The present invention relates to endoscopic devices and related methods. In particular, the present invention relates to endoscopic devices and methods used in, for example, an endoscopic fundoplication procedure for treatment of Gastroesophageal Reflux Disease (GERD). Gastroesophageal reflux occurs when stomach acid enters the esophagus. This reflux of acid into the esophagus occurs naturally in healthy individuals, but also may become a pathological condition in others. Effects from gastroesophageal reflux range from mild to severe. Mild effects include heartburn, a burning sensation experienced behind the breastbone. More severe effects include a variety of complications, such as esophageal erosion, esophageal ulcers, esophageal stricture, abnormal epithelium (e.g., Barrett's esophagus), and/or pulmonary aspiration. These various clinical conditions and changes in tissue structure that result from reflux of stomach acid into the esophagus are referred to generally as Gastroesophageal Reflux Disease (GERD). The physical interaction occurring between the gastric fundus 5 and the esophagus 3 also prevents gastroesophageal reflux. The gastric fundus 5 is a lobe of the stomach situated at the top of the stomach 7 distal to the esophagus 3. In asymptomatic individuals, the fundus 5 presses against the opening of the esophagus 3 when the stomach 7 is full of food and/or gas. This effectively closes off the esophageal opening to the stomach 7 and helps to prevent acid reflux back into the esophagus 3. More specifically, as the food bolus is immersed in gastric acid, it releases gas which causes the fundus 5 of the stomach 7 to expand and thereby exert pressure on the distal esophagus 3 causing it to collapse. The collapse of the esophagus lumen reduces the space for the stomach acid to splash past the closed esophagus lumen and thereby protect the proximal esophagus from its destructive contact. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Endoscopic instruments Inventor(s): Kawashima, Koichi; (Hachioji-shi, JP), Onuki, Yoshio; (Hino-shi, JP), Pasricha, Pankaj Jay; (Houston, TX), Shimonaka, Hideki; (Hachioji-shi, JP), Suzuki, Takayuki; (Yokohama-shi, JP), Tsukagoshi, Tsuyoshi; (Tokyo, JP) Correspondence: Kenyon & Kenyon; 1500 K Street, N.W., Suite 700; Washington; DC; 20005; US Patent Application Number: 20020156344 Date filed: April 3, 2002

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Abstract: An endoscopic instrument used to form an artificial valve for treating gastroesophageal reflux disease (GERD). Excerpt(s): This application claims the benefit of U.S. Provisional Application to Yoshia Onuki et al, entitled "Endoscopic Instruments," application No. 60/281,016 filed Apr. 4, 2001. The present invention relates to apparatuses for forming an artificial valve to treat gastroesophageal reflux disease (GERD). The incidence of GERD has increased recently. The main symptoms of GERD are heartburn and mucosal breaks in the esophagus. Although it is a benign disease, GERD is accompanied by serious pain, and often requires treatment. The main cause of GERD is decreased function of the lower esophageal sphincter (LES) at the bottom of the esophagus followed by reflux of acid into the esophagus. GERD is usually treated by administration of acid secretion controlling agent such as proton-pump inhibitor. Moderate GERD will improve and may be treated completely by medication. If, however, the LES function is damaged seriously or if anatomic problems such as hiatal hernias exist, treatment with medication is less effective, and becomes costly over an extended period of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Heartburn and reflux disease treatment apparatus Inventor(s): Forsell, Peter; (Menzingen, CH) Correspondence: Nixon & Vanderhye P.C.; 1100 North Glebe Road, 8th Floor; Arlington; VA; 22201; US Patent Application Number: 20020193842 Date filed: June 29, 2001 Abstract: A heartburn and reflux disease treatment apparatus comprises an electric stimulation device (56) adapted to engage the cardia sphincter (58) of a patient, who suffers from heartburn and reflux disease, and electrically stimulate the cardia sphincter to increase the sphincter tonus, so that the cardia completely closes. A control device (62) is provided for controlling a source of energy (64), which may or may not be implanted, to release electric energy for use in connection with the power of the stimulation device. Excerpt(s): Heartburn and reflux disease is a widespread medical problem. This is often due to hiatal hernia, i.e. a portion of the stomach immediately below the gastric fundus slides upwardly through the esophageal hiatus. In consequence, stomach acids and foods are regurgitated into the esophagus. In the late 1970s a prior art restriction device called Angelchik, according to U.S. Pat. No. 3,875,928, was used to operatively treat heartburn and reflux disease. However, the Angelchik restriction device had a major disadvantage in that it was not possible to adjust the size of the restriction opening after the operation. A further disadvantage was that the restriction device did not satisfactorily protect the esophagus and the surrounding area against injuries due to poor shape of the restriction device. Therefore, operations using the Angelchik stimulation device are no longer practised. An operation technique, semifundoduplicatio, is currently in use for treating heartburn and reflux disease. A most common operation is Nissen semi-fundoduplicatio, in which one takes the fundus of the stomach and makes a three-quarter of a turn around the esophagus and suture between the stomach and esophagus. Although this operation works fairly well it has three main disadvantages. Firstly, most patients' treated in accordance to "ad modum Nissen" lose their ability to belch. Secondly, many of these patients's get dysphagia, i.e. difficulties to

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swallow after the operation. Thirdly, it is not possible to adjust the food passageway in the esophagus or stomach in any way after the operation. Characteristic for these patients's is the variation of their problems over the day. For example, many patients have difficulties during the night when they lie down because of stomach acid leaking up into the esophagus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Honey-based composition for relief of occasional heartburn and digestive disorders Inventor(s): Postmes, Theo; (Maashicha, NL) Correspondence: Womble Carlyle Sandridge & Rice; P.O. Box 725388; Atlanta; GA; 31139-9388; US Patent Application Number: 20010006687 Date filed: December 20, 2000 Abstract: According to the present invention, a composition is provided including honey and raw food fibers. The composition's primary use is to relieve occasional heartburn and digestive disorders including GERD and stomach and intestine complaints. Further, the composition of the present invention may be processed into a compressed product. Among the many advantages of the composition of the present invention are that the composition normalizes the defective physiology of the digestion; the composition achieves the desired therapeutic effect quickly; and the composition is provided as a natural product without adverse side effects found with typical pharmaceutical products. Excerpt(s): This application claims foreign priority benefits under 35 U.S.C.sctn.119,.sctn.365 and/or.sctn.371 of the earlier filed Netherlands Patent Application No. 1013943, filed Dec. 23, 1999. The present invention generally relates to a composition, preferably a natural composition, for the relief of occasional heartburn and digestive disorders including gastroesophageal reflux disease (GERD) and stomach and intestine complaints. Indigestion, as well as heartburn, occurs frequently. Stomach pain and severe heartburn are, if they only occur from time to time, a normal deviance of the digestion physiology. Overweight, over eating, over consumption of alcohol, worry and stress are correlating factors to the appearance of disturbances in the digestion (dyspepsia). The over-production of acid is a characteristic of this disturbance, which can be remedied by reducing the production of acid or by neutralizing the stomach acid with antacids (e.g., with calcium carbonate and magnesium carbonate such as RENNIES). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Implantable particles for tissue bulking and the treatment of gastroesophageal reflux disease, urinary incontinence, and skin wrinkles Inventor(s): Boschetti, Egisto; (Croissy sur Seine, FR), Thomas, Richard; (Belmont, MA), Vogel, Jean Marie; (Boxborough, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020068089 Date filed: December 28, 2001 Abstract: The invention encompasses the treatment of urinary incontinence, gastroesophageal reflux disease and the amelioration of skin wrinkles using biocompatible hydrophilic cationic microparticles and a cell adhesion promoter. Excerpt(s): This application is a divisional of application Ser. No. 09/263,773, filed Mar. 5, 1999, now U.S. Pat. No. 6,335,028, the content of which is incorporated by reference. The present invention relates to tissue bulking, the treatment gastroesophageal reflux disease, urinary incontinence and the amelioration of skin wrinkles. Although gastroesophageal reflux is a normal physiological phenomenon, in some cases it is a pathophysiological situation that can result in a variety of symptoms which may become severe in extreme cases. Gastro-Esophageal Reflux Disease ("GERD"), describes a backflow of acidic and enzymatic liquid from the stomach to the esophagus. It causes burning sensations behind the sternum that may be accompanied by regurgitation of gastric acid into the mouth or even the lung. Complications of GERD which define the severity of the disease include esophageal tissue erosion, and esophageal ulcer wherein normal epithelium is replaced by a pathological tissue. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Individualization of therapy with gastroesophageal reflux disease agents Inventor(s): Leyland-Jones, Brian; (Miami, FL) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20030049204 Date filed: April 24, 2002 Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with GERD agents. Excerpt(s): This application is a new application which claims the benefit of U.S. Provisional Application No. 60/285,687, filed on Apr. 24, 2001. The entire teachings of the above application is incorporated herein by reference. The invention relates to a system and method for individualization of therapy with Gastroesophageal Reflux Disease (GERD) agents. More specifically, the present invention relates to the use of metabolic phenotyping in individualizing treatment with GERD agents. For the majority of drugs (or xenobiotics) administered to humans, their fate is to be metabolized in the liver, into a form less toxic and lipophilic with their subsequent excretion in the urine. Their metabolism involves two systems (Phase I and Phase II) which act consecutively: Phase I enzymes include the cytochrome P450 system which includes at least 20

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enzymes catalyzing oxidation reactions as well as carboxylesterase, amindases, epoxide hydrolase, quinine reductase, alcohol and aldehyde dehydrogenase, xanthine oxidase and flavin-containing monooxygenase. These enzymes are localized in the microsomal fraction. Phase II enzymes include the conjugation system which involves at least 5 enzymes including, N-acetyltransferases (NAT), UDP-glucoronyltransferases (UGT), sulfotransferases (SUT), and glutathione-S-transferases (GST). A detailed description of the complex human drug metabolizing systems is provided in Kumar and Surapaneni (Medicinal Res. Rev. (2001) 21(5):397-411) and patent application WO 01/59127 A2. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Instrument for applying a surgical fastener particularly for the transoral treatment of gastroesophageal reflux disease (GERD) Inventor(s): Kortenbach, Juergen A.; (Miami Springs, FL), McBrayer, Michael Sean; (Miami, FL), Sixto, Robert JR.; (Miami, FL), Slater, Charles R.; (Fort Lauderdale, FL), Smith, Kevin W.; (Coral Gables, FL) Correspondence: Lerner And Greenberg; PO Box 2480; Hollywooddddd; FL; 33022-2480; US Patent Application Number: 20040059349 Date filed: September 20, 2002 Abstract: A surgical instrument includes an end effector having a clevis and first and second jaws mutually rotatable between open and closed positions. The jaws are proximally directed and laterally displaced relative to a longitudinal axis of a control shaft of the instrument. The jaws hold first and second parts of a fastener, respectively. The first part includes a base having upstanding tissue piercing posts, and the second part includes another base defining apertures for receiving the posts, as well as a portion movable relative to the second base. When the upstanding posts are inserted into the apertures, the movable portion can be moved into a second configuration to lock the parts of the fastener together. The instrument is adapted to move the second part into the second configuration. A method for using the apparatus and fastener are also provided. Excerpt(s): The invention relates to surgical fasteners, endoscopic surgical instruments, and procedures. More particularly, the invention relates to surgical fasteners, endoscopic instruments, and procedures for the transoral plication and fastening together of portions of the stomach for the treatment of GERD. Gastroesophageal reflux disease (GERD) or persistent heartburn is caused by an improper relaxation of the lower esophageal sphincter (LES) that allows the frequent regurgitation of acidic stomach contents into the esophagus. If left untreated, chronic reflux may cause esophageal stricture, bleeding ulcers, perforation, and scarring. Continued reflux may lead to Barrett's esophagus, which involves changes in the cells that make up the esophagus and may lead to cancer. The current mode of treatment is primarily pharmacological starting with antacids and progressing to proton pump inhibitors (PPIs). The progression of the disease is noted by the development of a hiatal hernia caused by the stomach being forced into the thoracic cavity. The pharmacological treatment ends with double and triple dosing of PPIs. At the point that the patient is not responding to the PPIs, surgical intervention is often recommended. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Lower esophagus tissue modifier Inventor(s): Klein, Dean A.; (North Oaks, MN) Correspondence: Faegre & Benson Llp; 2200 Wells Fargo Center; 90 South 7th Street; Minneapolis; MN; 55402; US Patent Application Number: 20030161887 Date filed: October 25, 2002 Abstract: The present invention provides a method of modifying the lower esophagus by injecting biocompatible particles in a biocompatible carrier into a submucosal tissue site of the lower esophagus of a patient. The method may be used to treat gastroesophageal reflux disease by optimizing the closing function of the lower esophageal sphincter. Excerpt(s): Gastroesophageal reflux disease, or GERD, is a medical condition caused by the repeated backup or regurgitation of food and digestive fluid from the stomach into the esophagus. The most common symptoms suggestive of GERD are heartburn or acid indigestion. GERD can damage esophageal tissues, raising the risk of serious problems such as cancer of the esophagus. It is estimated that ten percent of Americans suffer from GERD on a daily basis. GERD occurs when a small ring of muscles called the lower esophageal sphincter ("LES") do not function properly. For example, at rest, the LES may maintain a high-pressure zone between 10 and 30 mm Hg above intragastric pressure. However, some patients suffering from GERD have an LES closing pressure of only 5 mm Hg. A weak or malfunctioning LES allows acidic stomach contents to back up into the esophagus. As the stomach contents flow back into the esophagus, the lining of the esophagus becomes irritated, creating a burning feeling in the chest. Left untreated, GERD can lead to frequent heartburn, difficulty swallowing, coughing, hoarseness, and more serious complications, such as narrowing of the esophagus, bleeding and a precancerous condition called Barrett's esophagus. There are a variety of treatments for GERD. The most common treatment involves lifestyle changes. For example, smoking, drinking, obesity, overeating, and diets high in fat and coffee all increase the chances of contracting GERD. There are also a wide variety of drugs that treat the symptoms associated with GERD. For example, antacids neutralize excess acid in the stomach to reduce irritation of the esophagus. H-2 receptor blockers reduce the amount of digestive acid that the body produces. An example of a relatively new class of drugs are Proton Pump Inhibitors that reduce acid production by affecting the final pathway of gastric acid secretion. Another class of drugs are Prokinetic agents, which treat GERD by shortening the digestion time and tightening the pressure that the LES places on the esophagus. Unfortunately, many of these drugs come with side effects, including nausea, constipation, diarrhea, cramps and potentially harmful interactions with other medications. Further, most of these medications do not treat the underlying cause of GERD, a malfunctioning LES. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Materials and methods for the treatment of gastroesophageal reflux disease Inventor(s): Becker, Cyrus; (Menlo Park, CA), Druzgala, Pascal; (Santa Rosa, CA), Milner, Peter G.; (Los Altos Hills, CA), Pfister, Jurg; (Los Altos, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20020025970 Date filed: June 7, 2001 Abstract: The subject invention provides novel compounds and compositions for the safe and effective treatment of gastroesophageal reflux and related conditions. In a preferred embodiment, the compositions of the subject invention comprise esterified cisapride derivatives. These compositions possess potent activity in treating gastroesophageal reflux disease and substantially reduce adverse effects associated with the administration of cisapride. These adverse effects include, but are not limited to, diarrhea, abdominal cramping and elevations of blood pressure and heart rate. Excerpt(s): The subject application claims priority to provisional application U.S. Ser. No. 60/209,926, filed Jun. 7, 2000. Cisapride is one of a class of compounds known as benzamide derivatives, the parent compound of which is metoclopramide. U.S. Pat. Nos. 4,962,115 and 5,057,525 (collectively "Van Daele" and incorporated by reference in their entireties) disclose N-(3-hydroxy-4-piperidenyl) benzamides of cisapride. Van Daele discloses that these compounds, the pharmaceutically acceptable acid addition salts thereof and the stereochemically isomeric forms thereof, stimulate the motility of the gastrointestinal system. As a class, these benzamide derivatives have several prominent pharmacological actions. The prominent pharmacological activities of the benzamide derivatives are due to their effects on the neuronal systems which are modulated by the neurotransmitter serotonin. The role of serotonin, and thus the pharmacology of the benzamide derivatives, has been broadly implicated in a variety of conditions for many years. Thus, research has focused on locating the production and storage sites of serotonin as well as the location of serotonin receptors in the human body in order to determine the connection between these sites and various disease states or conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Medicated chewing-gum Inventor(s): West, Douglas H.; (Lebanon, OH) Correspondence: Killworth, Gottman, Hagan & Schaeff, L.L.P.; One Dayton Centre; Suite 500; Dayton; OH; 45402-2023; US Patent Application Number: 20030118691 Date filed: January 2, 2003 Abstract: The present invention is directed to chewing-gum preparations which are particularly useful for treating gastroesophageal reflux disease. Typically, the chewinggum preparation comprises a chewing-gum base and more than one ingredient selected from the group consisting of an acid neutralizing agent, an anti-gas agent, and an acid production inhibitor, and desirably all three ingredients. The invention is also directed to a method for treating gastroesophageal reflux disease comprising the step of masticating a chewing-gum preparation including a gum base and more than one

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ingredient selected from the group consisting of an acid neutralizing agent, an anti-gas agent, and an acid production inhibitor, and desirably all three ingredients. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 08/790,528, filed Jan. 29, 1997. One of the most common gastrointestinal ailments to afflict modern man is gastroesophageal reflux disease (GERD). GERD includes such symptoms as heartburn, indigestion, sour stomach, dyspepsia and flatulent dyspepsia. The frequency of the occurrences of GERD is difficult to estimate, but it is reasonable to assume that a majority of individuals living in industrialized societies today suffer from it at one time or another. Dietary indiscretion appears on the surface to be the primary cause along with stress, but GERD actually has a multifactorial etiology. The extent of the problem is evidenced by the multitude of prescription and non-prescription remedies available to the sufferer and the billions of dollars spent annually on treatments for GERD. Multiple factors contribute to the occurrence of GERD. These factors include: efficacy of the anti-reflux mechanism; volume of gastric fluid; potency of the refluxed material; efficiency of esophageal clearance; and tissue resistance of the esophageal mucosa. The extent and severity of reflux esophagitis depends not on gastroesophageal reflux alone, but also upon the volume of gastric juice available to reflux, the potency of the refluxed material, the interval that the refluxed material remains in the esophagus, and the ability of the esophageal tissue to withstand injury and to repair itself after injury. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the treatment of gastroesophageal reflux disease Inventor(s): Gevas, Philip C.; (Key Biscayne, FL), Grimes, Stephen; (Davis, CA), Karr, Stephen; (Davis, CA), Michaeli, Dov; (Larkspur, CA) Correspondence: Howson And Howson; One Spring House Corporation Center; Box 457; 321 Norristown Road; Spring House; PA; 19477; US Patent Application Number: 20030068326 Date filed: December 6, 2002 Abstract: A method for the treatment of gastroesophageal reflux disease comprising a combination of active immunization with an anti-gastrin immunogenic composition with an antagonist which blocks or inhibits the gastric acid pump activity; or alternatively administering purified anti-gastrin antibodies with a H.sub.2 antagonist or proton pump inhibitor of the gastric acid producing enzyme system. Excerpt(s): This application in a continuation of U.S. patent application Ser. No. 09/700,378, filed Mar. 1, 2001, which is a national stage of PCT/US99/10734, filed May 14, 1999, which claims the benefit of the priority of U.S. Provisional Patent Application No. 60/085,610, filed May 15, 1998, now abandoned. Gastroesophageal reflux disease ("GERD") is a common and chronic disorder which requires long-term, even lifelong, therapy. GERD is commonly known as heartburn, and is characterized by a retrosternal burning sensation, and regurgitation of the stomach contents. About 40% of adults in the United States have experienced occurrences of the disease, and approximately 10% have daily troubling symptoms. GERD occurs when there is an abnormally prolonged contact time between the esophageal mucosa and refluxate, which is believed to be primarily gastric acid (DeVault, et al., Mayo Clinic Proc. 69.867-876, 1994 and Redmond, et al. In "Gastroesophageal Reflux Disease" Ronald Hinder ed., R. G. Landes Co., Ch. 1, pages 1-6, 1993). The regurgitation of the gastric contents and duodenal juice is believed

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to be due to either an incompetent lower esophageal sphincter or more frequently to an inappropriate sphincter relaxation at the time of transfer of the stomach contents between stomach and small intestine. The resultant reflux of acid and other materials from the stomach may induce pain or damage the esophageal mucosa. This damage to the esophageal mucosa may lead to esophagitis which is characterized by inflammation of the esophageal mucosa, bleeding, cytological changes, peptic esophageal stricture, esophageal ulcer and Barrett's metaplasia, depending on the severity of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of treating gastroesophageal reflux disease Inventor(s): Johnson, George M.; (Santa Ana, CA), Tsukashima, Ross; (San Diego, CA), Yurek, Matthew Thomas; (San Diego, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 91614; US Patent Application Number: 20020148475 Date filed: June 7, 2002 Abstract: Disclosed is an esophageal bulking device for implantation below the mucosa in the vicinity of the lower esophageal sphincter. Preferably, the bulking device comprises an expandable hydrogel implant. Also disclosed are methods of treating gastroesophageal reflux disease, by implanting an expandable bulking device below the mucosa in the vicinity of the lower esophageal sphincter. The bulking device may be subsequently explanted from the vicinity of the lower esophageal sphincter. Excerpt(s): The present application is a continuation of Ser. No. 09/651,751 filed on Aug. 30, 2000, which is a continuation of Ser. No. 09/524,478 filed on Mar. 13, 2000, now U.S. Pat. No. 6,338,345 which is a continuation-in-part of application Ser. No. 09/287,607 filed on Apr. 7, 1999, now U.S. Pat. No. 6,098,629. The present invention relates generally to the field of esophageal prosthetics. More specifically, a prosthesis delivery device is disclosed for submucosal insertion of a prosthetic bulking device. Gastroesophageal reflux is a physical condition in which stomach acids reflux, or flow back from the stomach into the esophagus. Frequent reflux episodes (two or more times per week), may result in a more severe problem known as gastroesophageal reflux disease (GERD). Gastroesophageal reflux disease is the most common form of dyspepsia, being present in approximately 40% of adults in the United States on an intermittent basis and some 10% on a daily basis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for protection of stratified squamous epithelium against injury by noxious substances and novel agents for use therefor Inventor(s): Hudson, Richard A.; (Toledo, OH), Orlando, Roy C.; (New Orleans, LA), Tillekeratne, Liyanaaratchinge M.V.; (Toledo, OH), Tobey, Nelia A.; (River Ridge, LA) Correspondence: Rebecca Shortle; Morrison & Foerster Llp; 755 Page Mill RD.; Palo Alto; CA; 94304-1018; US Patent Application Number: 20020052408 Date filed: July 5, 2001

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Abstract: Novel sulfate ester agents and the use of those agents for treating gastroesophageal reflux disease (GERD) are described, exemplary agents being of the formula: 1wherein X is --OCH.sub.2-- or --CH.sub.2O--; Y is a group pendant from X comprising at least one --OSO.sub.3R.sup.4 moiety, wherein R.sup.4 is H or a pharmaceutically acceptable cation; n is an integer from 1-3; and R.sup.1 and R.sup.2 are each independently selected from the group consisting of --H, a halogen with an atomic number from 9 to 53, --SO.sub.3R.sup.4, --NCS, --NCO, --NH(CO)--OR.sup.3, -NH(CS)SR.sup.3, --NH(C.dbd.NH)OR.sup.3, --NHCOCH.sub.2Cl, --NHCOCH.sub.2Br, --NHCO--CH.dbd.CH.sub.2, --NHC(O)--CF.sub.3, wherein R.sup.4 is H or a pharmaceutically acceptable cation. Excerpt(s): This application claims priority to U.S. provisional patent application No. 60/216,771, filed Jul. 7, 2000, which is incorporated herein by reference in its entirety. This invention relates to methods for protecting stratified squamous epithelium against injury by noxious substances. This invention also relates to novel sulfate ester agents useful in these methods. Specifically, these methods and agents may be used in the protection and treatment of tissues damaged by or susceptible to damage by noxious substances such as acid, more particularly in the treatment of gastroesophageal reflux disease (GERD) arising from acid injury. Gastroesophageal reflux (GER) is the effortless movement of gastric contents from the stomach to the esophagus. It is a physiologic process, occurring in everyone, many times a day throughout life and without symptoms or signs of tissue injury. However, beginning at about 35-40 years of age, GER is increasingly associated with the symptom of heartburn and morphologic injury to the esophagus. Indeed, a Gallup poll reported that up to 44% of adult Americans experience heartburn at least monthly and up to 10% have heartburn daily. The proximate cause for the transition from GER to gastroesophageal reflux disease (GERD) is the ability of noxious materials from the stomach to contact the esophagus with sufficient duration to result in damage to the epithelium. Moreover, it is well established that the major injurious agent within the refluxate is gastric acid, though the latter may be aided by the presence of pepsin within the refluxate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for the endoluminal treatment of gastroesophageal reflux disease (GERD) Inventor(s): Kortenbach, Juergen A.; (Miami Springs, FL), McBrayer, Michael Sean; (Miami, FL), Sixto, Robert JR.; (Miami, FL), Slater, Charles R.; (Fort Lauderdale, FL), Smith, Kevin W.; (Coral Gables, FL) Correspondence: Gordon & Jacobson, P.C.; 65 Woods End Road; Stamford; CT; 06905; US Patent Application Number: 20020078967 Date filed: December 6, 2001 Abstract: Methods of the invention include delivering a grasper, a clip applier, and an endoscope transorally to the site of fundoplication; grasping the fundus with the grasper (or similar device, e.g. corkscrew) and pulling it into the jaws of the clip applier; closing the jaws of the clip applier over the fundus and applying a clip to the fundus. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/931,528, filed Aug. 16, 2001, entitled "Methods and Apparatus for Delivering a Medical Instrument Over an Endoscope while the Endoscope is in a Body Lumen", the complete disclosure of which is hereby incorporated by reference herein. This application is also a

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continuation-in-part of application Ser. No. 09/891,775, filed Jun. 25, 2001, entitled "Surgical Clip", the complete disclosure of which is hereby incorporated by reference herein. This application also claims the benefit of provisional application Ser. No. 60/292,419, filed May 21, 2001, entitled "Methods and Apparatus for On-Endoscope Instruments Having End Effectors and Combinations of On-Endoscope and ThroughEndoscope Instruments". Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating ulcers and gastroesophageal reflux disease Inventor(s): Barron, Richard L.; (Trabuco Canyon, CA) Correspondence: Stephen Donovan; Allergan, INC.; 2525 Dupont Drive, T2-7h; Irvine; CA; 92612; US Patent Application Number: 20040086531 Date filed: November 5, 2002 Abstract: Methods for treating peptic ulcers and methods for treating gastroesophageal reflux disease by oral administration of a botulinum toxin. Excerpt(s): The present invention relates to methods for treating ulcers and/or for treating gastroesophageal reflux disease. In particular, the present invention relates to methods for treating peptic ulcers and for treating gastroesophageal reflux disease with a botulinum toxin. During normal digestion, food moves from the mouth down the esophagus into the stomach. The stomach produces hydrochloric acid and the enzyme pepsin to digest the food. From the stomach, food passes into the upper part of the small intestine, the duodenum, where digestion and nutrient absorption continue. An ulcer is a sore or lesion that forms in the lining of the stomach or duodenum where acid and pepsin are present. Ulcers in the stomach are called gastric or stomach ulcers. Ulcers in the duodenum are called duodenal ulcers. Collectively, ulcers in the stomach and duodenum are called peptic ulcers. Ulcers rarely occur in the esophagus or in the first portion of the duodenum, the duodenal bulb. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Preventive or therapeutic agents for gastric or esophageal regurgitation Inventor(s): Yamazaki, Satoshi; (Tokyo, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030130304 Date filed: November 8, 2002 Abstract: The compound of the following formula: 1wherein R.sup.1 and R.sup.2 independently represent a hydrogen atom or a lower alkyl group; A represents a group selected from the group consisting of 1-azabicyclo[3.2.2]nonyl group, 1azabicyclo[2.2.2]octyl group, or an N-oxide thereof, or a pharmaceutically acceptable salt thereof or a hydrate thereof has both improving effect on enterokinetic functions and suppressing effect on acid secretion, and also is highly safe. Accordingly, the substance is useful as preventive or therapeutic medicament for a gastroesophageal reflux disease.

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Excerpt(s): The present invention relates to a medicament comprising thieno[3,2b]pyridinecarboxamide derivative as an active ingredient which is useful for preventive and/or therapeutic treatment of a gastroesophageal reflux disease. Gastroesophageal reflux disease (hereafter referred to as "GERD") is a generic term of diseases with various digestive symptoms such as pyrosis, acid regurgitation, obstructed admiration, aphagia, pectoralgia, permeating feeling and the like sensibility caused by reflux in the esophagus and stagnation of gastric contents, duodenal juice, bile, pancreatic juice and the like. The term covers both of reflux esophagitis in which erosion and ulcers are endoscopically observed, and esophageal regurgitation-type non-ulcer dyspepsia (NUD) in which no abnormality is endoscopically observed. Examples of causes of GERD include intraesophageal reflux of gastric contents due to lowered contractibility of the lower esophageal sphincter, reduced resistance of esophageal mucosa to acid and/or pepsin, reduction of esophageal clearance after reflux, prolongation of gastric evacuation, esophageal hiatus hernia and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Reduction of heartburn episodes after ingestion of orange juice Inventor(s): Green, Nancy R.; (Bradenton, FL), Letourneau, Stephen A.; (Holmes Beach, FL), McArdle, Richard N.; (Bradenton, FL), McGill, Carla R.; (Sarasota, FL) Correspondence: Cook, Alex, Mcfarron, Manzo, Cummings & Mehler Ltd; Suite 2850; 200 West Adams Street; Chicago; IL; 60606; US Patent Application Number: 20020192309 Date filed: May 3, 2001 Abstract: Reducing heartburn episodes is achieved in individuals having an orange juice intolerance or food allergy. The orange juice product has a low titratable acidity which combines with a condition resulting after addition of a calcium source such as a calcium citrate source. Individuals prone to orange juice induced heartburn episodes experience a reduced incidence of these heartburn episodes. Excerpt(s): This invention relates to approaches for reducing heartburn episodes when an individual having an orange juice intolerance ingests orange juice according to the invention. The invention is achieved without any substantial negative impact on orange juice flavor or other important attributes. The heartburn reduction is achieved by orange juice which combines the features of being of a lower acid type while incorporating a calcium source such as in the form of a calcium citrate source. Numerous individuals have been known to experience negative effects upon ingesting different foods. A true food allergy occurs when the immune system of the individual overreacts to certain proteins in food. It is believed that hundreds of food ingredients can provoke an allergic reaction. Typical foods in this regard are nuts, peanuts, milk, eggs, fish, shellfish, soybeans and wheat. Foods such as these can lead to symptoms including nausea, hives, skin rash, nasal congestion, wheezing, and the like. However, most unpleasant reactions to food are caused not by allergies but by intolerances, which tend to be less severe than true food allergies. Typical in this regard are lactose intolerance, sulfite intolerance and intolerance to monosodium glutamate, red wine, chocolate and food coloring agents. Another intolerance of some frequency is manifested by gastral distress and/or digestive difficulties which certain individuals experience shortly after ingesting orange juice products. In some circles, it is generally assumed that the relatively high acidity of orange juice products is a primary contributor to these negative or unpleasant experiences with orange juice products for a

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small percentage of the population. For example, Kligerman et al U.S. Pat. No. 5,665,415 and No. 5,869,119, incorporated hereinto by reference, suggest that acidic foods or beverages such as coffee and other beverages can be combined with calcium glycerophosphate so as to raise the pH of the food or beverage by at least 0.5 pH units, such as to a pH of greater than 5.4, which typically is pH higher than desirable for superior tasting orange juice. This pH adjustment is said to reduce the tendency of the food or beverage to cause heartburn and other esophageal and/or gastrointestinal distress. This approach generally follows the conventional wisdom that ingesting antacids treats heartburn by helping to neutralize stomach acid. This approach suggests, in general, raising the pH of the food or beverage to well above 5. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Surgical clips particularly useful in the endoluminal treatment of gastroesophageal reflux disease (GERD) Inventor(s): Kortenbach, Juergen A.; (Miami Springs, FL), Sixto, Robert JR.; (Miami, FL) Correspondence: Gordon & Jacobson, P.C.; 65 Woods End Road; Stamford; CT; 06905; US Patent Application Number: 20020138086 Date filed: May 20, 2002 Abstract: Surgical clips which are particularly useful in the transoral invagination and fundoplication of the stomach to the esophagus. are disclosed. The clips include first and second arms joined by a bridge to form a substantially U-shape, and which are provided with a first structure adapted to prevent a movement of the clip in a direction perpendicular to a longitudinal axis of the clip after the clip is applied to tissue. In addition, the clips preferably also include a second structure adapted to prevent rotation of the clip about the longitudinal axis of the clip after the clip is applied to tissue. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 10/010,246, filed Dec. 6, 2001, which is a continuation-in-part of application Ser. No. 09/931,528, filed Aug. 16, 2001, entitled "Methods and Apparatus for Delivering a Medical Instrument Over an Endoscope while the Endoscope is in a Body Lumen", a continuation-in-part of application Ser. No. 09/891,775, filed Jun. 25, 2001, entitled "Surgical Clip", and a continuation-in-part of application Ser. No. 09/730,911, filed Dec. 6, 2000, entitled "Methods and Apparatus for the Treatment of Gastric Ulcers", the complete disclosures of all of which are hereby incorporated by reference herein in their entireties. This application is additionally related to co-owned application Ser. No. 10/010,096, filed Dec. 12, 2001, entitled "Flexible Surgical Clip Applier", the complete disclosure of which is hereby incorporated by reference herein. The invention relates to endoscopic surgical procedures and instruments. More particularly, the invention relates to surgical clips which are particularly useful in the transoral invagination and fundoplication of the stomach to the esophagus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Systems and methods employing a bite block insert for positioning and stabilizing external instruments deployed within the body Inventor(s): Gaiser, John W.; (Mountain View, CA), Utley, David S.; (Redwood City, CA), West, Scott; (Livermore, CA) Correspondence: Ryan Kromholz & Manion, S.C.; Post Office Box 26618; Milwaukee; WI; 53226; US Patent Application Number: 20020162555 Date filed: December 14, 2001 Abstract: Systems and methods are provided for positioning and stabilizing an external instrument during insertion of the instrument through the oral cavity (e.g., insertion of a catheter through the oral cavity and into the esophagus or cardia for treatment of gastroesophageal reflux disease (GERD)). The systems and methods provide a gripping tool for association with a bite block, capable of selectively moving between an open position in which the instrument may be inserted or removed, and a closed position in which the external instrument is held in a fixed position. Excerpt(s): The invention generally relates to systems and methods for inserting and securing the position of an external instrument, such as a catheter tube, in the body, e.g., through the oral cavity and into the esophagus for the treatment of gastric esophageal reflux disease (GERD). Procedures requiring insertion of an external instrument into the body, e.g., through the oral cavity into the esophagus, are known. Bite blocks are typically used to hole the patient's mouth open during these procedures. During these procedures, it also may be necessary to locate the instrument in an intended position. It may also be necessary to stabilize the instrument in an intended position. There remains a need for simple, cost-effective ways to introduce an instrument through the oral cavity to locate the instrument and to selectively maintain the instrument in a fixed and stable position during a given medical procedure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment for gastroesophageal disease Inventor(s): Milbocker, Michael T.; (Holliston, MA) Correspondence: Donald N. Halgren; 35 Central Street; Manchester; MA; 01944; US Patent Application Number: 20030188755 Date filed: April 9, 2002 Abstract: A system including an implantable polymer for increasing the dimensions of layers of tissue. In one embodiment, the implantable polymer is delivered transorally using a scope and injection needle. The system allows for visualization and injection of polymer into the lower esophageal sphincter. Methods of treating gastroesophageal reflux disease includes insertion of the distal portion of the injection needle into the esophageal tissue and injection of a polymer liquid to enlarge tissue dimensions. The polymer can be injected at several sites to distribute localized pressures and attain better distribution of the tissue bulking effect. Excerpt(s): This invention relates generally to a method to treat sphincters, and more particularly to a method to treat esophageal sphincters in mammalian patients as a remedy for Gastroesophageal disease. Gastroesophageal reflux disease (GERD) is a disorder of the lower esophageal sphincter which allows stomach contents to reverse

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flow into the distal portion of the esophagus during digestion. Complications associated with GERD include heartburn, pulmonary disorders, chest pain, esophageal ulcers, esophagitis, Barrett's esophagus, and esophageal carcinoma. Treatments for GERD include prescribed acid blockers for limiting gastric production of acid and acid neutralizers. The relief is generally short-term, and the drugs alleviate symptoms of GERD without correcting the underlying dysfunction of the esophageal sphincter. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of somatostatin receptor agonists in the treatment of human disorders of sleep hypoxia and oxygen deprivation Inventor(s): Young, Charles W.; (New York, NY) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20030083241 Date filed: October 25, 2002 Abstract: The invention relates to a method of treating diverse human disorders that may arise, in part, out of sleep hypoxia and oxygen deprivation occurring in the context of sleep apnea/hypopnea disturbances. The disorders that may be treated by the invention comprise gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, sudden infant death syndrome, and diverse neurologic conditions. The mode of treatment uses somatostatin receptor ligands (SstRLs), particularly somatostatin-receptor agonists. The invention concerns the method of treatment utilizing, and compositions comprising SstRLs and somatostatin receptor agonists, including agonists of the somatostatin receptor types 2 and 5, particularly, the type 2A receptor (SsR-2A), including octreotide and lanreotide. Excerpt(s): The invention relates to a method of using somatostatin receptor agonists to treat diverse human disorders of sleep hypoxia and oxygen deprivation, including but not limited to: 1) gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, and asthma; 2) obstructive sleep apnea (OSA), and OSA-associated conditions, including GER, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, median nerve compression neuropathy (carpal tunnel syndrome) and cognitive impairment; as well as sleep apnea-associated sudden infant death syndrome (SIDS), 3) central sleep apnea (CSA), as well as CSAassociated conditions, including GER, cardiomyopathy, cardioarrhythmia, congestive heart failure, and cognitive impairment; 4) mixed pattern sleep apneas, including but not limited to post-vascular occlusion sleep apnea, dementia-associated sleep apnea, amyotrophic lateral sclerosis-associated sleep apnea, myasthenia gravis-associated sleep apnea, and alcoholism-related sleep apnea; 5) excess calpain-activation disorders in tissues where the injured cell population expresses somatostatin receptors; including, but not limited to the central nervous system, peripheral nerves, heart, liver, kidney, and gastrointestinal tract. Various documents are cited in this text. Citations in the text can be by way of a citation to a document in the reference list, e.g., by way of an author(s) and document year, whereby full citation in the text is to a document that may or may not also be listed in the reference list. There is no admission that any of the various documents cited in this text are prior art as to the present invention. Any document having as an author or inventor person or persons named as an inventor herein is a document that is not by another as to the inventor of entity herein. All documents cited

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in this text ("herein cited documents") and all documents cited or referenced in herein cited documents are hereby incorporated herein by reference. 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 gastroesophageal reflux disease, 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 “gastroesophageal reflux disease” (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 gastroesophageal reflux disease. You can also use this procedure to view pending patent applications concerning gastroesophageal reflux disease. 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 GASTROESOPHAGEAL REFLUX DISEASE Overview This chapter provides bibliographic book references relating to gastroesophageal reflux disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on gastroesophageal reflux disease 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 “gastroesophageal reflux disease” (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 gastroesophageal reflux disease: •

Gastroesophageal Reflux Disease and Airway Disease Source: New York, NY: Marcel Dekker, Inc. 1999. 376 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016-0602. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $175.00 plus shipping and handling. ISBN: 0824702301. Summary: An ever increasing body of evidence supports the importance of gastroesophageal reflux disease (GERD) as a significant factor in both upper and lower airway diseases. This textbook presents 13 chapters that explore this connection. Chapters cover the embryologic origins of the relationship between GERD and airway disease, the role of nerves and the potential influence of GERD in inflammation in asthma, the diagnosis of GERD, its otolaryngologic manifestations, GERD as a major

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factor in chronic cough, the mechanisms of interaction between GERD and airway disease, the medical treatment for GERD and airway disease, the surgical treatment for GERD with emphasis on respiratory symptoms, GERD and airways disease in children and adolescents, the respiratory complications of reflux disease in infants, the oral manifestations of GERD, and special considerations, including pregnancy and aging. Each chapter includes extensive references, and the text concludes with author and subject indexes. •

Healing Heartburn Source: Baltimore, MD: Johns Hopkins University Press. 2002. 208 p. Contact: Available from Johns Hopkins University Press. 2715 North Charles Street, Baltimore, MD 21218-4363. (410) 516-6900. Fax (410) 516-6968. E-mail: [email protected]. Website: www.press.jhu.edu. PRICE: $17.95 for paperback; plus shipping and handling. ISBN: 801868696. Summary: Nearly everyone has experienced heartburn, the sensation of burning discomfort in the chest, often after eating a large meal. Heartburn is just one symptom of the disorder known as acid reflux disease, or gastroesophageal reflux disease (GERD), a condition in which stomach acid repeatedly washes up into the esophagus or remains in the esophagus too long. This book offers a comprehensive guide to GERD, covering diagnostic tests, a step-by-step approach to treatment, the effectiveness of medications, complications and how to avoid them, and special considerations for pregnant women and for children. The book features illustrations, questionnaires, patient vignettes, answers to commonly asked questions, and a list of additional resources. A glossary of terms and a subject index conclude the volume.

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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

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perspective on health care. A subject index concludes the volume. 397 references. (AAM). •

Fire Inside: Extinguishing Heartburn and Related Symptoms Source: New York, NY: W.W. Norton and Company. 1996. 192 p. Contact: Available from W.W. Norton and Company, Inc. 500 Fifth Avenue, New York, NY 10110. (212) 354-5500. PRICE: $23.00. ISBN: 0393038637. Summary: This book offers readers an abundance of information on heartburn, related symptoms, and complications. The introductory chapter relates facts and myths about heartburn, and includes a historical perspective of the diagnosis and treatment of the condition. Chapter 2 offers lifestyle modifications that may provide simple heartburn relief. Chapters 3 and 4 discuss acid and antacids, and acid disease (gastroesophageal reflux disease, or GERD). Chapter 5 updates readers on current medications available for heartburn. Chapter 6 explores the relationship between asthma and acid reflux. Chapter 7 outlines the ear, nose, and throat complications that can arise from acid reflux conditions. And Chapter 8 helps readers differentiate between 'indigestion' and cardiovascular problems (heartburn or heart attack). The concluding chapter reviews the medications and lifestyle recommendations available and encourages readers to take charge of their heartburn. The book concludes with a glossary and a subject index.

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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).

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

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

Controlling heartburn (Patient counseling library) by American College of Physicians; ISBN: 0891190252; http://www.amazon.com/exec/obidos/ASIN/0891190252/icongroupinterna

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Curing Common Complaints: From Bad Breath to Fatigue, Heartburn and Tooth Stains : The Best Doctor-Tested Tips to Relieve Everyday Health Concerns (The Family Home Remedies Collection) by Prevention Magazine (Editor); ISBN: 0875962629; http://www.amazon.com/exec/obidos/ASIN/0875962629/icongroupinterna

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Indigestion, Heartburn & Stomach Ulcer: Bonfire in the Belly by Macey Casebeer; ISBN: 0964554658; http://www.amazon.com/exec/obidos/ASIN/0964554658/icongroupinterna

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Nouvelle Yenta Cookbook: Farewell to Heartburn Hotel by Jeannie Sakol; ISBN: 0942637488; http://www.amazon.com/exec/obidos/ASIN/0942637488/icongroupinterna

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

Barrett's Esophagus and Adenocarcinoma Source: in Freston, J.W. Diseases of the Gastroesophageal Mucosa: The Acid-Related. Totowa, NJ: The Humana Press, Inc. 2001. p.167-175. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail: [email protected] PRICE: $99.50, plus shipping and handling. ISBN: 089603965X. Summary: Barrett's esophagus is a change in the esophageal epithelium (lining), recognized on endoscopy, which is confirmed at biopsy to contain intestinal metaplasia (growth of tissue). This chapter on Barrett's esophagus and adenocarcinoma (cancer) is from a text that emphasizes the diagnosis and treatment of gastric mucosal diseases. Topics include a definition of Barrett's esophagus and its classification (short segment and long segment), when to look for Barrett's esophagus, diagnostic strategies, a definition of dysplasia, surveillance and monitoring of patients with Barrett's esophagus, and therapeutic options. The authors conclude by noting that Barrett's

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esophagus is the precursor lesion of adenocarcinoma of the esophagus, so surveillance endoscopy is warranted. Surveillance endoscopy intervals are based on the presence and grade of dysplasia. Early endoscopy allows for early intervention and improved outcome. Therapy for Barrett's esophagus entails complete symptomatic relief of GERD with proton pump inhibitor (PPI) therapy or fundoplication. 3 figures. 1 table. 25 references. •

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, 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.

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Gastroesophageal Reflux Disease in Adults Source: in PDxMD. PDxMD Gastroenterology. St. Louis, MO: Elsevier Science. 2003. p. 193-227. Contact: Available from Elsevier Science. Customer Service Department, 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 535-9935. Email: [email protected]. Website: www.elsevierhealth.com. PRICE: $39.95. ISBN: 932141049. Summary: Gastroesophageal reflux disease (GERD) is characterized by the passive reflux (return) of gastric (stomach) contents into the esophagus that causes symptoms or histopathologic changes in the esophagus. Typical symptoms are heartburn, acid regurgitation, and dysphagia. This chapter on GERD in adults is from a book on gastroenterology that offers concise, action-oriented recommendations for primary care medicine. The chapter covers summary information and background on the condition,

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and comprehensive information on diagnosis, treatment, outcomes, and prevention. Specific topics covered include the ICD9 code, urgent action, synonyms, cardinal features, causes (etiology), epidemiology, differential diagnosis, signs and symptoms, associated disorders, investigation of the patient, appropriate referrals and consultations, diagnostic considerations, clinical tips, treatment options, patient management issues, drug therapies, prognosis, complications, and how to prevent recurrence. The information is provided in outline and bulleted format for ease of accessibility. The final section of the chapter offers resources, including related associations, key references, and the answers to frequently asked questions (FAQs). 35 references. •

Esophageal Surgery for Gastroesophageal Reflux Disease, Achalasia, and Cancer Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 140-150. 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: Minimally invasive surgery has revolutionized the treatment of gastroesophageal reflux disease (GERD) and achalasia (swallowing disorders). This chapter on esophageal surgery for GERD, achalasia, and esophageal cancer is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The authors discuss the indications, techniques, results, and complications of these surgical techniques. The authors describe the possible impact on esophageal cancer that earlier detection and treatment of GERD may realize. That is, effective treatment of GERD can prevent the development of Barrett's esophagus, and timely treatment of Barrett's esophagus can prevent progression to esophageal cancer. In addition, emerging evidence suggests that neoadjuvant therapy in association with surgery has the potential to improve outcome for patients with adenocarcinoma of the esophagus. Improved surgical technique and postoperative care have also resulted in a decrease in both morbidity and mortality associated with esophageal resection. Laparoscopic antireflux surgery allows control of reflux without the need for further medical therapy in most patients. The authors note that patients with achalasia should be referred to esophageal surgeons with expertise in minimally invasive surgery. Pneumatic dilation should be used as first line treatment when this expertise is not available, to treat patients who do not desire surgery, and for the management of strictures following esophagomyotomy. 6 figures. 1 table. 66 references.

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What Is Gastroesophageal Reflux Disease? Source: in Cheskin, L.J. and Lacy, B.E. Healing Hearburn. Baltimore, MD: Johns Hopkins University Press. 2002 p. 3-10. Contact: Available from Johns Hopkins University Press. 2715 North Charles Street, Baltimore, MD 21218-4363. (410) 516-6900. Fax (410) 516-6968. E-mail: [email protected]. Website: www.press.jhu.edu. PRICE: $17.95 for paperback; plus shipping and handling. ISBN: 801868696. Summary: Nearly everyone has experienced heartburn, the sensation of burning discomfort in the chest, often after eating a large meal. Heartburn is just one symptom of the disorder known as acid reflux disease, or gastroesophageal reflux disease

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(GERD), a condition in which stomach acid repeatedly washes up into the esophagus or remains in the esophagus too long. This introductory chapter is from a book that offers a comprehensive guide to GERD. In this chapter, the authors review a fairly typical case study, using this case to discuss symptoms, over-the-counter medications (antacids), prescription medications, diagnostic tests that are used to confirm GERD, the epidemiology of GERD, and risk factors, notably lifestyle factors, for GERD. The authors sketch out the four steps of treatment that are generally recommended to relieve the symptoms of GERD. •

Dysphagia, Odynophagia, Heartburn, and Other Esophageal Symptoms Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 93-101. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Occasional esophageal complaints are common and usually are not harbingers of disease. However, frequent or persistent dysphagia (swallowing difficulty), odynophagia (painful swallowing), or heartburn immediately suggests an esophageal problem that necessitates investigation and treatment. This chapter on dysphagia, odynophagia, heartburn, and other esophageal symptoms is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include the mechanisms and classification of dysphagia, odynophagia, the symptoms and mechanisms of heartburn, globus sensation, chest pain, and respiratory, ear, nose and throat, and cardiac symptoms of esophageal problems. The author stresses that in particular, gastroesophageal reflux disease (GERD) may manifest with atypical complaints and should not be missed, because it is readily treatable. The chapter includes a mini-outline with page citations, full-color illustrations, and extensive references. 1 figure. 5 tables. 73 references.

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Complications of Gastroesophageal Reflux Disease Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 44-52. 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: This chapter on the complications of gastroesophageal reflux disease (GERD) is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The squamous epithelium (lining) of the esophagus lacks the protective or rehealing capabilities of the duodenal and stomach linings after exposure to gastric acid. Exposure of the esophagus, especially in repeated instances, can perpetuate and extend the initial peptic injury. Deep peptic ulcers of the esophagus can stimulate fibrous tissue deposition with stricture formations. In some patients, the ulcerated lining is replaced by metastatic mucosal tissue (Barrett's esophagus) that can predispose the patient to adenocarcinoma (cancer). For reasons that are not clear, esophageal complications of

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GERD occur predominantly in white people and appear to be strikingly uncommon in Black and Asian persons. 5 figures. 4 tables. 75 references. •

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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CHAPTER 6. MULTIMEDIA ON GASTROESOPHAGEAL REFLUX DISEASE Overview In this chapter, we show you how to keep current on multimedia sources of information on gastroesophageal reflux disease. 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 gastroesophageal reflux disease is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “gastroesophageal reflux disease” 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 “gastroesophageal reflux disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on gastroesophageal reflux disease: •

GERD: Beyond Heartburn Source: Princeton, NJ: Films for the Humanities and Sciences. 1998. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail: [email protected]. Website: www.films.com. PRICE: $99.00 plus shipping and handling. Order number BXA7956. Summary: Every year, more than 19 million Americans suffer from gastroesophageal reflux disease (GERD). This potentially serious digestive disorder is often mistaken for heartburn by sufferers. In this program, Dr. Malcolm Robinson, president and director of the Oklahoma Foundation for Digestive Research, and David Earnest, Professor of Medicine, Gastroenterology Section, University of Arizona Health Sciences Center, discuss the symptoms of GERD, its physiological causes, and what can be done to treat

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it. The video is set up like a news program, with a reporter narrating the information. Topics covered include a definition of GERD and how it differs from simple heartburn; the typical symptoms (burning discomfort behind the breastbone, chest pain, hoarseness, and asthma); the physiology of GERD; treatment options, including lifestyle modifications, H2 receptor antagonists, proton pump inhibitors, prokinetic drugs, and antireflux surgery; how antacids work to neutralize acid in the esophagus; esophageal complications, including Barrett's esophagus, ulceration, bleeding, and stricture (narrowing); tests used for diagnosis, including barium x ray, endoscopy, and pH measurement; and how to know which specialty of medicine handles GERD and other gastrointestinal problems (minor problems can be handled by a primary care physician, but more severe complaints should be seen by a gastroenterologist). The program features numerous interviews with patients, who describe how it feels to have GERD, and graphics that depict its mechanisms of action. •

Disease Management and Outcomes Analysis in Gastroesophageal Reflux Disease (GERD) Source: Chapel Hill, NC: Health Sciences Consortium. 1996. (videocassette). Contact: Available from Health Sciences Consortium. Distribution Department, 201 Silver Cedar Court, Chapel Hill, NC 27514-1517. (919) 942-8731. Fax (919) 942-3689. Email: [email protected]. PRICE: $296.25 for members, $395 for nonmembers. Catalog number Catalog Number N961-VI-027. Summary: Gastroesophageal reflux disease (GERD) is one of the most widespread, difficult to manage, and expensive illnesses in the United States. Approximately 100 million people suffer from heartburn on a monthly basis and up to 10 million on a weekly basis. The cost of medications, office and clinic visits, diagnostic procedures, and followup examinations total over $3 billion a year. This videotape program presents a faculty of physicians and pharmacists who discuss recent advances in the diagnosis and treatment of patients with GERD. In addition, the program focuses on cost effectiveness of various treatment strategies. The program is intended for use by medical students, residents, and professionals in gastroenterology, clinical pharmacy, outcomes analysis, and managed care. (AA-M).

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Extinguishing Heartburn Source: Madison, WI: University of Wisconsin Hospitals and Clinics, Department of Outreach Education. 1995. (videocassette). Contact: Available from University of Wisconsin Hospital and Clinics. Picture of Health, 702 North Blackhawk Avenue, Suite 215, Madison, WI 53705-3357. (800) 757-4354 or (608) 263-6510. Fax (608) 262-7172. PRICE: $19.95 plus shipping and handling; bulk copies available. Order number 091395A. Summary: Heartburn, or acid indigestion, can limit daily activities and productivity. This videotape is one in a series of health promotion programs called 'Picture of Health,' produced by the University of Wisconsin. In this program, moderated by Mary Lee and featuring gastroenterologist John Wyman, the common symptoms, diagnosis, and management of heartburn are covered. Dr. Wyman stresses that any chest pain requires a medical evaluation to rule out other causes such as heart disease. Dr. Wyman defines heartburn as a symptom of gastroesophageal reflux disease (GERD), which is the reflux or return of stomach contents into the esophagus. Dr. Wyman reviews the anatomy and physiology of the gastrointestinal (GI) tract, including the lower esophageal sphincter (LES) and LES pressures. Risk factors for GERD include certain

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diet and lifestyle choices, smoking, obesity, pregnancy, and the regular use of certain foods and beverages. The program then reviews tips to control heartburn, including elevate the head of the bed, lose any excess weight, do not lie down immediately following a meal, and decrease portion size at mealtimes. Dr. Wyman recommends that people coping with heartburn eliminate acidic foods and any other foods that cause individual symptoms from their diet. The program briefly covers the use of antacids and the role of hiatal hernia and reflux. The program concludes by referring viewers to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). •

Nighttime Heartburn Source: Bethesda, MD: American Gastroenterological Association (AGA). 2001. (videocassette). Contact: Available from American Gastroenterological Association (AGA). Digestive Disease Week (DDW), 7910 Woodmont Avenue, Suite 700, Bethesda, MD 20814-3015. (301) 272-0022. Fax (301) 654-3978. Website: www.ddw.org. PRICE: Single copy free to patient. Summary: These instructional materials support the Nighttime Heartburn Relief Effort, an initiative aimed at bringing important messages about nighttime heartburn to Americans, and educating physicians and their patients about the potential dangers associated with nighttime heartburn, as well as treatment options. The program was launched in response to a recent survey that examined prevalence, severity, and sufferers' satisfaction with current treatments and attitudes toward the condition. The materials define gastroesophageal reflux (the return of stomach contents, including acidic gastric juices, back up into the esophagus), and note that when sleeping and in the prone position, there is more pressure on the esophagus and the esophagus is less able to clear the acid reflux. And, because acid may linger longer in the esophagus at night, nighttime heartburn can also lead to inflammation, scarring, and a resulting risk for asthma and cancer. The program reviews treatment options, including lifestyle changes and medications, and helps viewers know when to contact their health care provider for diagnosis and additional treatment help.

•

Heartburn Sufferers: Stop Taking Chances Source: Arlington, VA: American College of Gastroenterology. 199x. (videorecording). Contact: Available from American College of Gastroenterology. 4900 B South 31st Street, Arlington, VA 22206. (800) 478-2876. PRICE: Single copy free. Summary: This patient education videotape explains the basics of heartburn and gastroesophageal reflux disease (GERD). Gastroesophageal reflux is a physical condition in which acid from the stomach flows backward up into the esophagus. Frequent problems with reflux (two or more times per week), food sticking, or blood or weight loss, may indicate the more severe problem of GERD. The program discusses causes of heartburn and GERD, treatments for infrequent heartburn, and complications of GERD. Discussion of treatment options for GERD covers lifestyle modification, medications often prescribed (H2 receptor antagonists, proton pump inhibitors, and promotility agents), and surgery. Other topics include the effectiveness of different therapies for GERD, the role of gastroenterologists, diagnostic tests (upper GI series, endoscopy, esophageal manometry or esophageal pH), and the link between duration of heartburn and severity of esophageal disease. The program emphasizes that heartburn is a common but not trivial problem, and encourages readers to consult their health care

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providers for ongoing problems with heartburn. The program features Dr. Joel Richter from The Cleveland Clinic. •

Esophagogastrectomy Using the Ivor Lewis Technique for Treatment of Barrett's Esophagus with Stricture and Severe Mucosal Dysplasia Source: Research Triangle Park, NC: Glaxo, Inc. 199x. Contact: Available from Glaxo Video Library. 5 Moore Drive, Research Triangle Park, NC 27709. (800) 824-2896. PRICE: Single copy free; available to health care professionals only. Item Number GVL329. Summary: This videotape presents the case of a 60-year-old man with long-standing reflux esophagitis who developed Barrett's esophagus as a result. Dr. Louis Del Guercio demonstrates esophagogastrectomy using the Ivor Lewis technique for treatment of Barrett's esophagus with stricture and severe mucosal dysplasia. (AA-M).

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CHAPTER 7. PERIODICALS AND NEWS ON GASTROESOPHAGEAL REFLUX DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover gastroesophageal reflux disease.

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

Heartburn may not reflect gastroesophageal reflux disease severity Source: Reuters Medical News Date: March 12, 2004

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•

FDA approves TAP's Prevacid for treating heartburn in children Source: Reuters Industry Breifing Date: August 05, 2002

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Pediatric gastroesophageal reflux disease responds to surgery Source: Reuters Medical News Date: May 25, 2001

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Heart problems associated with heartburn drug Source: Reuters Health eLine Date: January 24, 2000

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Progression of Barrett's esophagus related to presence of hiatal hernia Source: Reuters Medical News Date: December 24, 1999

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Self-medication for frequent and persistent heartburn may mask serious disease Source: Reuters Medical News Date: December 28, 1998

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Holiday heartburn may be serious Source: Reuters Health eLine Date: December 25, 1998

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Chronic heartburn can indicate major illness Source: Reuters Health eLine Date: December 01, 1998 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 “gastroesophageal reflux disease” (or synonyms) into the search box, and click on “Search

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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 “gastroesophageal reflux disease” (or synonyms). If you know the name of a company that is relevant to gastroesophageal reflux disease, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “gastroesophageal reflux disease” (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 “gastroesophageal reflux disease” (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 gastroesophageal reflux disease: •

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

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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.

Academic Periodicals covering Gastroesophageal Reflux Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to gastroesophageal reflux disease. In addition to these sources, you can search for articles covering gastroesophageal reflux disease that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for gastroesophageal reflux disease. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with gastroesophageal reflux disease. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-

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interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to gastroesophageal reflux disease: Acetaminophen, Sodium Bicarbonate, and Citric Acid •

Systemic - U.S. Brands: Bromo-Seltzer http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202005.html

Antacids •

Oral - U.S. Brands: Advanced Formula Di-Gel; Alamag; Alamag Plus; Alenic Alka; Alenic Alka Extra Strength; Alka-Mints; Alkets; Alkets Extra Strength; Almacone; Almacone II; AlternaGEL; Alu-Cap; Aludrox; Alu-Tab; Amitone; Amphojel; Antacid Gelcaps; Antacid Liquid; Antacid Liquid Double Strength; Basaljel; Calglycine; Chooz; Dicarbosil; Di-Gel; Equilet; Foamicon; Gaviscon; Gaviscon Extra Strength Relief Formula; Gaviscon-2; Gelusil; Genaton; Genaton Extra Strength; Kudrox Double Strength; Losopan; Losopan Plus; Lowsium Plus; Maalox; Maalox Antacid Caplets; Maalox Heartburn Relief Formula; Maalox Plus; Maalox Plus, Extra Strength; Maalox TC; Magnalox; Magnalox Plus; MagOx 400; Mallamint; Maox 420; Marblen; Mi-Acid; Mi-Acid Double Strength; Mintox; Mintox Extra Strength; Mygel; Mygel II; Mylanta; Mylanta Double Strength; Mylanta Gelcaps; Nephrox; Phillips'; Phillips' Chewable; Phillips' Concentrated Double Strength; Riopan; Riopan Plus; Riopan Plus Double Strength; Rolaids; Rulox; Rulox No. 1; Rulox No. 2; Rulox Plus; Simaal 2 Gel; Simaal Gel; Tempo; Titralac; Titralac Extra Strength; Titralac Plus; Tums; Tums Anti-gas/Antacid; Tums E-X; Tums Ultra; Uro-Mag http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202047.html

Aspirin, Sodium Bicarbonate, and Citric Acid •

Systemic - U.S. Brands: Alka-Seltzer Effervescent Pain Reliever and Antacid; Flavored Alka-Seltzer Effervescent Pain Reliever and Antacid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202073.html

Bismuth Subsalicylate •

Oral - U.S. Brands: Bismatrol; Bismatrol Extra Strength; Pepto-Bismol; PeptoBismol Easy-to-Swallow Caplets; Pepto-Bismol Maximum Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202092.html

Caffeine •

Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html

Cisapride •

Systemic - U.S. Brands: Propulsid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202672.html

Doxycycline •

Dental - U.S. Brands: Atridox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203716.html

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Esomeprazole •

Systemic - U.S. Brands: Nexium http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500275.html

Histamine H 2-receptor Antagonists •

Systemic - U.S. Brands: Axid; Axid AR; Mylanta AR Acid Reducer; Pepcid; Pepcid AC Acid Controller; Pepcid I.V.; Pepcid RPD; Tagamet; Tagamet HB; Zantac; Zantac EFFERdose Granules; Zantac EFFERdose Tablets http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202283.html

Lansoprazole •

Systemic - U.S. Brands: Prevacid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202787.html

Metoclopramide •

Systemic - U.S. Brands: Metoclopramide Intensol; Octamide; Reglan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202364.html

Omeprazole •

Systemic - U.S. Brands: Prilosec http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202423.html

Pantoprazole •

Systemic - U.S. Brands: Protonix http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500064.html

Quinidine •

Systemic - U.S. Brands: Cardioquin; Quinaglute Dura-tabs; Quinidex Extentabs; Quin-Release http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202498.html

Rabeprazole •

Systemic - U.S. Brands: AcipHex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500054.html

Sodium Bicarbonate •

Systemic - U.S. Brands: Arm and Hammer; Bell/ans; Citrocarbonate; Pure Baking Soda; Soda Mint http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202525.html

Sucralfate •

Oral - U.S. Brands: Carafate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202533.html

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

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

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

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

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approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for gastroesophageal reflux disease: •

porfimer (trade name: Photofrin) http://www.rarediseases.org/nord/search/nodd_full?code=1194

•

Profimer (trade name: Photofrin) http://www.rarediseases.org/nord/search/nodd_full?code=1229

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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

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•

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

•

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “gastroesophageal reflux disease” (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 13051 148 298 14 33 13544

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

13

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

14

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

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

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

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

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

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

•

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

18 Adapted 19

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

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

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

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Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseases.html 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 Throat Disorders http://www.nlm.nih.gov/medlineplus/throatdisorders.html Voice Disorders http://www.nlm.nih.gov/medlineplus/voicedisorders.html

Within the health topic page dedicated to gastroesophageal reflux disease, the following was listed: •

Diagnosis/Symptoms Esophageal Muscle Test (Manometry) Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com//invoke.cfm?id=AN00340 Gastric Analysis Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/gastricanaly.pdf Heartburn or Heart Attack? Source: National Heartburn Alliance http://www.heartburnalliance.org/section3/1030.jsp Upper GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/uppergi/index.htm

•

Treatment Medication Chart Source: National Heartburn Alliance http://www.heartburnalliance.org/section3/1045.jsp

•

Nutrition Heartburn-Smart Choices When Eating Out Source: National Heartburn Alliance http://www.heartburnalliance.org/section4/7113.jsp Stocking the Pantry Source: National Heartburn Alliance http://www.heartburnalliance.org/section4/7110.jsp

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Stop and Select Guide Source: National Heartburn Alliance http://www.heartburnalliance.org/section4/6008.jsp •

Organizations American College of Gastroenterology http://www.acg.gi.org/ American Gastroenterological Association http://www.gastro.org/ National Heartburn Alliance http://www.heartburnalliance.org/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

•

Prevention/Screening Heartburn-Friendly Cooking Techniques Source: National Heartburn Alliance http://www.heartburnalliance.org/section4/7111.jsp Tips to Combat Exercise-Induced Heartburn Source: National Heartburn Alliance http://www.heartburnalliance.org/section3/exercise.jsp

•

Statistics 2003 Survey Results: The Burn Factor Source: National Heartburn Alliance http://www.heartburnalliance.org/nosection/2003SurveyResults.jsp National Heartburn Alliance 2000 Survey Results Source: National Heartburn Alliance http://www.heartburnalliance.org/nosection/results0.jsp

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 gastroesophageal reflux disease. 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

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options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Gastroesophageal Reflux Disease: More Than Heartburn Source: American Family Physician. 60(3): 885-886. September 1, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: Gastroesophageal reflux disease (GERD) is the most common esophageal disease. Besides the typical presentation of heartburn and acid regurgitation, either alone or in combination, GERD can cause atypical symptoms. This patient education handout reviews these symptoms, and how they are treated. Sometimes GERD can cause problems in the throat, making the patient feel as if there is a lump in the throat or creating an urge to clear the throat. GERD can also cause burning sensations in the mouth, trouble swallowing, dry mouth, bad breath, or even pain in the ears. It is diagnosed by the symptoms and then treated with traditional medications. Patients are encouraged to accompany any drug therapy with lifestyle changes, including limiting certain foods, stopping smoking, not drinking alcohol, losing weight (if needed), eating smaller meals, avoiding eating and drinking about 4 hours before going to bed, and raising the head of the bed. The handout briefly reviews the medications that may be used and the differences between the prescription and over the counter versions of these drugs.

•

Barrett's Esophagus Source: Riviera Beach, FL: AmeriPath, Inc. 2004. 2 p. Contact: Available from AmeriPath, Inc. 7289 Garden Road, Suite 200, Riviera Beach, FL 33404. (800) 330-6565. Email: [email protected]. Website: www.ameripath.com. PRICE: Single copy free; Full-text available online at no charge. Summary: Gastroesophageal reflux is a clinical condition in which contents normally found within the stomach regurgitate or reflux back into the esophagus, the tube connecting the mouth to the stomach. Untreated, reflux can cause ulcers and strictures (abnormal narrowing) or a change in the lining calls of the esophagus (Barrett's esophagus). This fact sheet helps readers understand Barrett's esophagus, a condition of changed cell structure in the esophagus that is associated with an increased risk of cancer. The fact sheet reviews the treatment options for Barrett's esophagus, including upper endoscopy for reflux, medical or surgical treatment for reflux, and follow up endoscopy to monitor for Barrett's; lifestyle changes that may help to reduce the symptoms of gastroesophageal reflux; and recommended questions to ask of one's physician. The fact sheet concludes with a list of sources of additional information, primarily the web site addresses of professional and voluntary organizations. 1 figure.

•

Heartburn Facts Source: Bethesda, MD: American Gastroenterological Association. 200x. 1 p. Contact: Available from American Gastroenterological Association. 4930 Del Ray Avenue, Bethesda, MD 20814. (301) 654-2055. Fax (301) 654-5920. E-mail: [email protected]. Website: www.gastro.org. PRICE: Contact organization for print copies.

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Summary: Heartburn is the most common symptom of a condition known as gastroesophageal reflux disease (GERD). The burning sensation or pain in the chest from heartburn can extend from the breastbone and move upward to the neck and throat, often leaving a bitter or acid taste. This fact sheet offers a series of basic information about heartburn. Topics include the symptoms of heartburn and GERD, how common these conditions are, the causes of GERD, complications of GERD and heartburn, and treatment options. The fact sheet offers a list of lifestyle modifications that can help address symptoms of infrequent heartburn. Patients with regular or chronic heartburn are encouraged to consult a health care provider. The fact sheet concludes with the website address of the American Gastroenterological Association (www.gastro.org). •

Understanding Heartburn and Reflux Disease Source: Indianapolis, IN: Eli Lilly and Company. 1993. 6 p. Contact: Available from Eli Lilly and Company. Lilly Corporate Center, Indianapolis, IN 46285. (317) 276-2000. PRICE: Single copy free. Summary: This booklet describes gastroesophageal reflux disease (GERD) and some of its symptoms, including heartburn. Topics include the anatomy and function of the stomach and esophagus; habits and conditions that can worsen reflux symptoms; factors that influence muscle valve pressure; symptoms to watch for; complications; diagnostic methods; and treatment options, including lifestyle adjustments, medication, and surgery. The booklet stresses that maintaining a positive attitude, working in tandem with one's health care provider, and complying with treatment advice are the best ways to manage reflux disease. 4 figures. 1 table. 11 references.

•

'I'm Taking Medicine for Frequent Heartburn. Why Am I Still Suffering?': A Patient Information Resource About Symptomatic Acid Reflux Disease Source: [Wayne, PA]: Astra Merck Inc. 1997. 15 p. Contact: Available from Astra Merck Inc. (800) 336-9992. PRICE: Single copy free. Summary: This booklet provides readers with basic information about heartburn and gastroesophageal reflux disease (GERD). The brochure encourages readers to ask their physicians about omeprazole (Prilosec), a drug therapy for heartburn and other symptoms associated with GERD. The brochure notes that if heartburn is present two or more times a week, GERD may be present. The author outlines the incidence of heartburn, the symptoms of GERD (heartburn, sour or bitter taste, difficult or painful swallowing), the causes of GERD symptoms, why GERD symptoms occur so frequently, how the stomach makes acid, and the action of acid pump inhibitors, such as omeprazole. GERD symptoms happen when juices containing harsh acid back up from the stomach into the esophagus. Included with the brochure is the package insert information from Prilosec. The brochure is illustrated with humorous, colorful line drawings of a variety of patients with heartburn and GERD. Blank space is available for notes or questions to ask the health care provider. (AA-M).

•

Barrett's Esophagus: A Problem Caused by GERD Source: San Bruno, CA: StayWell Company. 2000. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $ 17.95 for 50 copies; plus shipping and handling; bulk copies available. Order number 9780.

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Summary: This brochure describes Barrett's esophagus, a condition in which part of the lining of the esophagus near the stomach has changed. This change is caused by the acid reflux that occurs with gastroesophageal reflux disease (GERD). The changed lining is not cancer, but it can lead to cancer. The brochure reviews the symptoms of GERD, including heartburn, sour tasting fluid in the mouth, frequent burping or belching, and symptoms that get worse after eating, bending over, or lying down. Barrett's esophagus is often found when a test for another problem is done. The brochure describes endoscopy, a test that is often used to diagnose Barrett's esophagus. The brochure explains how readers with Barrett's esophagus or GERD can prevent further damage through lifestyle changes and medications. One sidebar describes GERD and includes an illustration of the anatomy involved. Readers are encouraged to participate in the recommended program of followup and monitoring of their condition, which usually includes an endoscopy every 2 years. The brochure is illustrated with full color drawings. 5 figures. •

Is It GERD? What You Need to Know About Gastroesophageal Reflux Disease Source: Atlanta, GA: Pritchett and Hull Associates, Inc. 1998. 4 p. Contact: Available from Pritchett and Hull Associates, Inc. 3440 Oakcliff Road, NE, Suite 110, Atlanta, GA 30340. (800) 241-4925. PRICE: $20.00 for pack of 50. Summary: This brochure familiarizes readers with the symptoms of gastroesophageal reflux disease (GERD), a chronic condition in which food or acid from the stomach flows back up into the esophagus. Written in nontechnical language, the brochure briefly reviews the anatomy and physiology of the stomach and esophagus and describes how heartburn and GERD can occur. The next section of the brochure describes the symptoms of GERD, including a burning feeling in the throat, a bitter, acid taste in the mouth, trouble swallowing, acid reflux, choking at night, weight loss, blood (in vomit or stool), and chest pain. The brochure helps readers determine if they need to consult with a health care provider. The brochure concludes with a list of seven lifestyle changes that might help to ease heartburn problems: raise the head of the bed, avoid certain foods and drinks, change eating and sleeping habits, lose weight, don't wear clothes that are tight around the waist, take medicines as prescribed, don't smoke, and avoid alcohol. The brochure is illustrated with line drawings. 5 figures.

•

Sometimes Heartburn is More Than Just Heartburn: Sometimes It's GERD (Gastroesophageal Reflux Disease) Source: Wayne, PA: Astra Merck. 1996. 4 p. Contact: Available from Astra Merck Information Center. 725 Chesterbrook Boulevard, Wayne, PA 19087-5677. (800) 236-9933 or (610) 695-1000. PRICE: Single copy free; bulk copies available. Summary: This brochure helps readers to differentiate between occasional mild heartburn or acid indigestion and the more serious problem of gastroesophageal reflux disease (GERD). The brochure first describes the symptoms of common heartburn and notes that the feeling of discomfort or burning tends to not last long, to be easily relieved with antacids or acid reducers, and to be prevented by dietary modifications. However, symptoms that do not fit into this description may be indicative of GERD. The brochure then describes GERD, notes its symptoms, and lists seven questions with which readers can self-diagnose their heartburn problems. The brochure also provides a series of helpful hints for managing GERD, in addition to medical treatment, by modifying lifestyle activities including dietary modification (what one eats and drinks,

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as well as when food intake occurs), weight loss, smoking cessation, avoiding drug interactions that may contribute to GERD, and raising the head of one's bed. The back cover of the brochure reprints the seven self-diagnostic questions contained inside. •

Gastroesophageal Reflux Disease (GERD) Source: Camp Hill, PA: Chek-Med Systems, Inc. 199x. [2 p.]. Contact: Available from Chek-Med Systems, Inc. 200 Grandview Avenue, Camp Hill, PA 17011-1706. (800) 451-5797 or (717) 761-1170. Fax (717) 761-0216. PRICE: $22.00 per pack of 50 brochures; 3 pack minimum. Summary: This brochure provides patients with a simple explanation of gastroesophageal reflux disease (GERD), the reflux or return of gastric (stomach) acid up the esophagus. Constant exposure to stomach acid can irritate the lining of the esophagus and cause other medical problems. At the lower end of the esophagus, where it enters the stomach, is a strong muscular ring called the lower esophageal sphincter (LES). The LES should remain tightly closed, except to allow food and liquid to pass into the stomach. The severity of GERD is determined by how weakened the LES is, and the amount and duration of acid refluxed into the esophagus. Frequent heartburn is the most common symptom; other symptoms can include sour or bitter taste in the mouth, hoarseness, repeated need to clear the throat, wheezing or coughing (especially at night), and worsening of symptoms after eating, or when bending over or lying down. Complications occur when GERD is severe or longstanding, and can include inflammation, ulcers, bleeding, anemia, narrowing of the esophagus, and Barrett's esophagus. Endoscopy is the most important test for patients with GERD; other tests that may be useful include esophageal manometry, and 24 hour pH testing. Initial treatment is with lifestyle changes, including diet and weight loss; drug therapy is used for patients who still have symptoms after lifestyle changes are implemented. Some patients will need surgery to strengthen the LES. The brochure concludes that a good medical program can almost always be developed to successfully treat the patient with GERD. 2 figures.

•

Understanding Gastroesophageal Reflux Disease (GERD) and Getting the Most Relief from Your Treatment Program Source: Salt Lake City, UT: Astra Merck, Inc. 1994. [8 p.]. Contact: Available from Astra Merck, Inc. 175 West 2700 South, Salt Lake City, UT 84115. (800) 208-1122. PRICE: Single copy free. Summary: This brochure provides readers with basic information about gastroesophageal reflux disease (GERD) and encourages the use of the enclosed symptom diary to help manage the disease. In patients with GERD, the harsh gastric juices from the stomach back up (reflux) into the esophagus (the muscular tube that carries food from the throat to the stomach). In people with GERD, the lower esophageal sphincter (LES), where the stomach and esophagus meet, is not working properly. The brochure emphasizes that GERD is not the patient's fault and cautions that GERD can lead to serious complications if it is not treated. The brochure also notes that communicating with one's health care provider is an important step towards living more comfortably with GERD. This includes discussing with the doctor how often symptoms are present, how they affect lifestyle, what increases or decreases symptoms, and whether the symptoms are still present during drug therapy. The latter half of the brochure consists of a diary designed to help patients identify and record this information to share with their physician. The diary provides a form to record time,

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symptom, the potential trigger (e.g., certain foods, or lying down), and whether or not antacid use was required. The diary includes space to record up to five episodes per day for four weeks. The brochure is written in nontechnical language and is illustrated with colorful line drawings. •

Heartburn: Nothing to do with the Heart Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders (IFFGD). 2000. [2 p.]. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217-8076. (888) 964-2001 or (414) 964-1799. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $1.00 for nonmembers; single copy free to members. Summary: This brochure reviews heartburn, defined as a burning sensation in the chest behind the breastbone. The author first reviews the terminology and differentiates between heartburn and dyspepsia (pain in the upper abdomen that resembles that of a peptic ulcer), then describes how heartburn is caused. When gastric (stomach) acids escapes back from the stomach into the esophagus (gastroesophageal reflux), it irritates or damages the esophagus, resulting in heartburn. The author describes the role of the lower esophageal sphincter (LES), which acts as a gate or valve between the esophagus and stomach, and what happens when the LES is weakened or malfunctioning. The author discusses the importance of eating smaller meals and not lying down immediately after a meal, in order to prevent reflux. In addition, certain foods compromise the sphincter's ability to prevent reflux; these foods differ from person to person, but many recognize fats, onions, and chocolate as particularly troublesome. The author reviews other conditions (such as overweight) that can make heartburn worse and summarizes the drugs that may be used to help treat heartburn. One sidebar summarizes basic facts about GERD. The brochure concludes with a brief description of the International Foundation for Functional Gastrointestinal Disorders (IFFGD), a nonprofit education and research organization (www.iffgd.org).

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GI Focus: Gastroesophageal Reflux Disease Source: Arlington, VA: American College of Gastroenterology. 1990. 2 p. Contact: Available from American College of Gastroenterology. 4900 B South 31st Street, Arlington, VA 22206-1656. (703) 820-7400. PRICE: Single copy free. Summary: This fact sheet presents update information about gastroesophageal reflux disease (GERD). Topics include the clinical symptoms and diagnosis of GERD; factors affecting GERD, including problems with the lower esophageal sphincter (LES); diagnostic tests; and therapeutic options. The fact sheet includes practical suggestions for treatments designed to reduce symptoms and minimize esophageal damage.

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Functional Heartburn Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders. 1997. 1 p. 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. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $0.50.

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Summary: This fact sheet provides basic information about functional heartburn, a disorder characterized by episodes of burning discomfort in the chest, behind the breastbone. There is no evidence of inflammation in the lining of the esophagus, nor of other disease. The discomfort generally comes in waves, occurs after meals, and can be accompanied by belching, regurgitation, or dyspeptic symptoms such as upper abdominal discomfort, bloating, or an early feeling of being full. If the symptoms of functional heartburn are episodic, short lasting, and well controlled with antacids, then diagnostic tests are not needed. With more severe symptoms, diagnostic tests will be performed to rule out esophagitis and gastroesophageal reflux disease (GERD). The author describes the possible interactions between stress and reflux or heartburn symptoms. The fact sheet concludes with a discussion of treatment strategies ranging from lifestyle changes to medications. Relaxation therapy may also prove useful for patients with functional heartburn symptoms. (AA-M). •

Gastroesophageal Disease (Hiatal Hernia and Heartburn) Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse. 2001. 6 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (800) 891-5389 or (301) 6543810. Fax (301) 634-0716. E-mail: [email protected]. Website: www.niddk.nih.gov. PRICE: Full-text available online at no charge; single copy free; bulk copies available. Order number: DD-160. Summary: This fact sheet provides information on gastroesophageal reflux disease (GERD), a digestive disorder that affects the lower esophageal sphincter (LES) that connects the esophagus with the stomach. Written in a question-and-answer format, the fact sheet addresses causes, symptoms, treatment, and long-term complications of GERD. Specific topics include the role of hiatal hernia; how dietary and lifestyle choices may contribute to GERD; heartburn pain and how to control it; non-pharmaceutical treatment options for GERD; and diagnostic tests used to establish a diagnosis of GERD, including upper GI series, endoscopy, the Bernstein test, and esophageal manometry. The fact sheet also includes a description of the National Digestive Diseases Information Clearinghouse. 2 figures. 4 references.

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Gastroesophageal Reflux Disease Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders (IFFGD). 2000. [2 p.]. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217-8076. (888) 964-2001 or (414) 964-1799. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $1.00 for nonmembers; single copy free to members. Summary: This fact sheet reviews gastroesophageal reflux disease (GERD), a disorder of gastrointestinal (GI) motility that occurs when acidic gastric (stomach) contents reflux, or go back up, into the esophagus. Repeated or prolonged exposure of the lining of the esophagus to this reflux can cause symptoms (such as heartburn) and tissue damage. GERD has been linked to asthma, and may possibly cause Barrett's esophagus. Diagnosis can be made solely on symptoms, or may include endoscopy, esophageal pH monitoring, and esophageal manometry. Treatment for GERD has three goals: reduce reflux, relieve symptoms, and allow the esophagus to heal. Most people with GERD have mild disease and can control it through lifestyle changes and medication. Over the

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counter (OTC) preparations such as antacids, alginic acid, or over the counter H2 blockers can help relieve mild intermittent symptoms. People with more severe GERD may need prescription strength H2 blockers or proton pump inhibitors. Surgery, notably fundoplication and dilation, can be used to treat complications. One sidebar asks readers five simple questions that act as a basic screening for the symptoms and presence of GERD. •

Coping with Heartburn and Reflux Source: Research Triangle Park, NC: Glaxo Pharmaceuticals. 1992. 1 p. Contact: Available from Glaxo Pharmaceuticals. Five Moore Drive, Research Triangle Park, NC 27709. (919) 248-2100. PRICE: Single copy free. Summary: This fact sheet, in the form of a small poster, lists nine recommendations designed to help people cope with heartburn and reflux. The fact sheet provides information on the following topics: avoiding certain foods; limiting intake of certain beverages, particularly those with caffeine; weight loss; eating moderately; careful timing of exercise; timing of meals; smoking; elevating the bed; and consulting a health care provider. A simple line drawing illustrates each of the nine suggestions.

•

Gastroesophageal Reflux Disease: A Look at Medical Treatment and Laparoscopic Surgery Source: San Bruno, CA: Krames Communications. 1997. 16 p. Contact: Available from Krames Communications. Order Department, 1100 Grundy Lane, San Bruno, CA 94066. (800) 333-3032. Fax (415) 244-4512. PRICE: $1.95 per copy; bulk discounts available. Summary: This patient education booklet provides information about the medical and laparoscopic treatment for gastroesophageal reflux disease (GERD). GERD can sometimes be controlled with simple lifestyle changes and medication; if symptoms persist, surgery may be indicated. Topics include the causes of GERD, treatment options, normal digestion and digestion with GERD, how GERD can progress, diagnostic tests, lifestyle changes, medical treatment for GERD, dilatation procedures, preparing for surgery, the risks and complications of surgery for GERD, the techniques used in laparoscopic surgery, and postoperative recovery and followup at home. The book is illustrated with colorful anatomical drawings and pictures of some of the treatment recommendations.

•

Is It Just a Little Heartburn or Something More Serious?: Understanding GERD Source: Arlington, VA: American College of Gastroenterology. 199x. 12 p. Contact: Available from American College of Gastroenterology. 4900 B South 31st Street, Arlington, VA 22206. (800) 478-2876. PRICE: Single copy free; bulk copies available. Summary: This patient education brochure explains the basics of heartburn and gastroesophageal reflux disease (GERD). Gastroesophageal reflux is a physical condition in which acid from the stomach flows backward up into the esophagus. Frequent problems with reflux (two or more times per week), food sticking, or blood or weight loss, may indicate the more severe problem of GERD. The brochure discusses causes of heartburn and GERD, treatments for infrequent heartburn, and complications of GERD. Discussion of treatment options for GERD covers lifestyle modification, medications often prescribed (H2 receptor antagonists, proton pump inhibitors, and

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promotility agents), and surgery. Other topics include the effectiveness of different therapies for GERD, the role of gastroenterologists, diagnostic tests (upper GI series, endoscopy, esophageal manometry or esophageal pH), and the link between duration of heartburn and severity of esophageal disease. The brochure emphasizes that heartburn is a common but not trivial problem, and encourages readers to consult their health care providers for ongoing problems with heartburn. With effective treatment, most patients can become symptom free, avoid potential complications, and enjoy a restored quality of life. The back cover of the brochure contains a test for readers to determine if they might have GERD. 1 figure. 1 table. (AA-M). •

Heartburn: Hints on Dealing with the Discomfort Source: Kansas City, MO: American Academy of Family Physicians. 1994. 4 p. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. PRICE: $22.00 for 100 copies for members, $33.00 for 100 copies for nonmembers. Summary: This patient education brochure helps readers understand heartburn and how they can deal with the discomfort it may cause. Heartburn is a burning feeling in the lower chest, along with a sour or bitter taste of food in the throat and mouth. It usually occurs after eating a big meal or while lying down. Heartburn is caused by stomach contents (acid) going back up into the esophagus; this is called reflux. The stomach acid can irritate the esophagus and cause the feeling of burning pain. The brochure describes hiatus hernia, factors that can add to heartburn, complications that can arise because of heartburn, tips on preventing heartburn, the use of antacids, how to know when to consult a health care provider regarding heartburn problems, medications that can be used, and the indications for surgery. Most people get fast, short-term relief with antacids. Three kinds of medications might be used to treat heartburn. H2 blockers (Axid, Pepcid, Tagamet, Zantac) lower how much acid the stomach makes. Omeprazole (Prilosec) completely stops the stomach from making acid. Metoclopramide (Reglan) reduces reflux. Surgery is only needed when symptoms are very bad and don't go away after medicine and other measures have been tried. Simple line drawings illustrate the stomach and esophagus. 2 figures. 3 tables. (AA-M).

•

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.

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Gastroesophageal Reflux Disease Diet Source: Camp Hill, PA: Chek-Med Systems, Inc. 1995. 2 p.

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Contact: Available from Chek-Med Systems, Inc. 200 Grandview Avenue, Camp Hill, PA 17011. (800) 451-5797. Fax (717) 761-0216. PRICE: $0.55 each, plus shipping (as of 1995). Order no. D-3. Summary: This patient education brochure, one of a series of 17 brochures, provides dietary recommendations for patients with gastroesophageal reflux disease (GERD). The brochure explains the purpose of a special diet for GERD; summarizes relevant nutrition facts; and lists special considerations for GERD, including both dietary and lifestyle recommendations. The brochure concludes with a list of food groups and items from each group that are recommended and those that are to be avoided. The brochure is printed in two colors and contains graphics. •

Living Comfortably With Heartburn Source: Patient Care. 30(8): 43. April 30, 1996. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This patient education handout briefly describes recommendations for living comfortably with heartburn. Topics include a definition of reflux (heartburn), treatment options, the role of environmental changes (such as propping up the head of the bed, dietary changes, and exercise), and when to consult a health care provider about reflux symptoms. 2 figures.

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Gastroesophageal Reflux Disease: Understanding and Controlling an Uncomfortable Problem Source: San Bruno, CA: Krames Communications. 1993. 8 p. Contact: Available from Krames Communications. 1100 Gundy Lane, San Bruno, CA 94066-3030. (800) 666-0198 or (415) 742-0400. PRICE: Single copy free. Summary: This patient information booklet presents an introduction to gastroesophageal reflux disease (GERD). Topics include the medical evaluation of GERD, including the patient's history, physical examination, and laboratory tests; lifestyle changes that may provide relief from GERD, including eating habits, smoking and drinking alcohol, elevating the head of the bed, losing weight, and the impact of pregnancy; and relief through medications, both over-the-counter and prescription medications. The booklet is written in clear, easy-to-understand language and copiously illustrated with full-color, drawings.

•

Living with GERD: Controlling the Symptoms of Heartburn Due to GERD Source: Indianapolis, IN: Eli Lilly and Company. 1995. 7 p. Contact: Available from Eli Lilly and Company. Lilly Corporate Center, Indianapolis, IN 46285. (800) 545-5979. PRICE: Single copy free. Summary: This pocket-sized patient information booklet provides information on controlling the symptoms of heartburn from gastroesophageal reflux disease (GERD). It describes the common causes of GERD, including food and lifestyle factors that may contribute to the problem. In addition, it addresses diagnostic tests, treatment options, and the importance of treatment for GERD. The booklet concludes with a section of questions for readers to ask themselves as a way to monitor their progress in managing GERD. 2 figures. 1 table. 6 references.

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Motility: The Forgotten Factor in Gastroesophageal Reflux Disease: Question and Answer Booklet Source: Titusville, NJ: Janssen Pharmaceutica, Inc. 1995. 9 p. Contact: Available from Janssen Pharmaceutica, Inc. 1125 Trenton-Harburton Road, P.O. Box 200, Titusville, NJ 08560. (800) 526-7736. PRICE: Single copy free. Summary: This question-and-answer booklet provides information for general practice physicians on gastroesophageal motility disease (GERD), specifically about the role of motility. Topics include how abnormal motility relates to the etiology of GERD; lower esophageal sphincter (LES) competence; the role of acid hypersecretion in the pathophysiology of GERD; delayed gastric emptying; times of day when patients are more prone to episodes of GERD; symptoms; eliciting a patient history from a patient suspected of suffering from GERD; diagnostic procedures; and treatments, including lifestyle modifications and nonsystemic therapy, initial pharmacotherapy, profound acid suppression, and antireflux surgery. The booklet concludes with the patient insert information for cisapride tablets (Propulsid). The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “gastroesophageal reflux disease” (or synonyms). The following was recently posted: •

Guidelines for surgical treatment of gastroesophageal reflux disease (GERD) Source: Society of American Gastrointestinal Endoscopic Surgeons - Medical Specialty Society; 1998 February (revised 2001 Jun); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3147&nbr=2373&a mp;string=symptomatic+AND+hiatal+AND+hernia

•

Management of gastroesophageal reflux disease (GERD) Source: University of Michigan Health System - Academic Institution; 2002 March; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3372&nbr=2598&a mp;string=gastroesophageal+AND+reflux+AND+disease Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

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Gastroesophageal Reflux Disease (GERD) Summary: This consumer health information document provides basic information about Gastroesophageal Reflux Disease (GERD) -- commonly called acid indigestion. Source: American College of Gastroenterology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3886

•

Have You Heard of GERD? Summary: This consumer health information brochure focuses on gastroesophageal reflux disease as it relates to children. Symptoms, prognosis and treatment are discussed. Source: Nemours Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3854 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 gastroesophageal reflux disease. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. 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

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

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

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

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

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

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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 gastroesophageal reflux disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with gastroesophageal reflux disease. 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 gastroesophageal reflux disease. 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 “gastroesophageal reflux disease” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “gastroesophageal reflux disease”. 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 “gastroesophageal reflux disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “gastroesophageal reflux disease” (or a synonym) into the search box, and click “Submit Query.”

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

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

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

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

21

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

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

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

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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/

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

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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/

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

Finding Medical Libraries

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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 gastroesophageal reflux disease: •

Basic Guidelines for Gastroesophageal Reflux Disease Barrett's esophagus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001143.htm Cancer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001289.htm Down syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000997.htm Esophageal spasm Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000289.htm 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

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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 Gastroesophageal reflux disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000265.htm Gerd Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000265.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Heartburn prevention Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002101.htm Hiatal hernia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001137.htm Peptic ulcer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000206.htm •

Signs & Symptoms for Gastroesophageal Reflux Disease Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Belching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003080.htm Black, tarry stools Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003130.htm Bloating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003123.htm Blood in the stools Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003130.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Difficulty swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Dysphagia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm

Online Glossaries 195

Early satiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003127.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Hoarseness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003054.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 Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Obesity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003101.htm Overweight Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003101.htm Pain when swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003116.htm Pulmonary disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000066.htm Sore throat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003053.htm Stomach acid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Swallowing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm

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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 Vomiting blood Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003118.htm Wheezing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003070.htm •

Diagnostics and Tests for Gastroesophageal Reflux Disease ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Barium swallow Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003816.htm Bernstein test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003897.htm 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 Differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.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 Eosinophils Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003649.htm Esophageal manometry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003884.htm Esophageal pH monitoring Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003401.htm Esophagogastroduodenoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003888.htm

Online Glossaries 197

Gastric acid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003883.htm GI series Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003816.htm PRA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003698.htm Stool guaiac Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003393.htm Throat swab culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003746.htm Ulcer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003225.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 Upper GI series Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003816.htm Urine culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003751.htm •

Nutrition for Gastroesophageal Reflux Disease Caffeine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002445.htm Coffee Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002445.htm Fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm

•

Surgery and Procedures for Gastroesophageal Reflux Disease Nissen fundoplication Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002925.htm

•

Background Topics for Gastroesophageal Reflux Disease Burn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000030.htm

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Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.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 Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Relieved by Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002288.htm Symptomatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002293.htm Weight reduction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001940.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

199

GASTROESOPHAGEAL REFLUX DISEASE 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] 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] Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1. [NIH] Achlorhydria: A lack of hydrochloric acid in gastric juice despite stimulation of gastric secretion. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Actin: Essential component of the cell skeleton. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerophagia: A condition that occurs when a person swallows too much air. Causes gas and

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frequent belching. [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] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]

Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] 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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [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] 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] 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]

Dictionary 201

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] 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 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] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [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] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve

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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] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] 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] Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Anticholinergics: Medicines that calm muscle spasms in the intestine. Examples are dicyclomine (dy-SY-kloh-meen) (Bentyl) and hyoscyamine (HY-oh-SY-uh-meen) (Levsin). [NIH]

Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU]

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Antrectomy: An operation to remove the upper portion of the stomach, called the antrum. This operation helps reduce the amount of stomach acid. It is used when a person has complications from ulcers. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [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] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH]

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Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] Barium swallow: A series of x-rays of the esophagus. The x-ray pictures are taken after the person drinks a solution that contains barium. The barium coats and outlines the esophagus on the x-ray. Also called an esophagram. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] 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]

Benzamides: Benzoic acid amides. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] 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 Reflux: Reflux of bile mainly into the upper digestive tract, but also into the pancreas. [NIH]

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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] 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] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] 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 Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] 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

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of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [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] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brash: An uneasy burning sensation in the stomach and associated with the eructation of an acid fluid. [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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] 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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH]

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Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] 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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [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] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It

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differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell 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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] 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.

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This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [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] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [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] 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] 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] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical series: A case series in which the patients receive treatment in a clinic or other medical facility. [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

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enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] 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] Competency: The capacity of the bacterium to take up DNA from its surroundings. [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

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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 biological problems including manipulation of models and datasets. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH]

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Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] 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] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] 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] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH]

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Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] 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.

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[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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuresis: Increased excretion of urine. [EU] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of

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dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [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 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] Duodenal Ulcer: An ulcer in the lining 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] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using

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scientific method or theory. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [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] 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] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

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

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] 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] 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 health-

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related event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Eructation: The ejection of gas or air through the mouth from the stomach. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] 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 Perforation: A dilated vessel in the lower end of the esophagus that result from portal hypertension. [NIH] Esophageal Stricture: A narrowing of the esophagus often caused by acid flowing back from the stomach. This condition may require surgery. [NIH]

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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] Esophagram: A series of x-rays of the esophagus. The x-ray pictures are taken after the person drinks a solution that contains barium. The barium coats and outlines the esophagus on the x-ray. Also called a barium swallow. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] 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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] 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] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or

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between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [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] Food and Beverages: Edible or potable substances. [NIH] Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] 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] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] 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 Bypass: Surgical procedure in which the stomach is transected high on the body. The resulting proximal remnant is joined to a loop of the jejunum in an end-to-side anastomosis. This procedure is used frequently in the treatment of morbid obesity. [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.

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[NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [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 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] Gastroplasty: Surgical treatment of the stomach or lower esophagus used to decrease the size of the stomach. The procedure is used mainly in the treatment of morbid obesity and to correct defects in the lower esophagus or the stomach. Different procedures employed include vertical (mesh) banded gastroplasty, silicone elastomer ring vertical gastroplasty and horizontal banded gastroplasty. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [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] Globus Sensation: A constant feeling of a lump in the throat. Usually related to stress. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH]

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Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] 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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] Halitosis: An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health 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] Health Promotion: Encouraging consumer behaviors most likely to optimize health

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potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

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]

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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] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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

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acid can result in impaired hydroxyproline formation. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [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] Hypotension: Abnormally low blood pressure. [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] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large

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amounts of antibody. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

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Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] 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] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [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] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques.

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[EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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] Kinetic: Pertaining to or producing motion. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large

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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 Diseases: General or unspecified disorders of 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] Lead Poisoning: Disease caused by the gradual accumulation of a significant body burden of lead. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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]

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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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [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]

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MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [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

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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] 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] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [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 Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient

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populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myenteric: On stimulation of an intestinal segment, the segment above contracts and that below relaxes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [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] Neoadjuvant Therapy: Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment. [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]

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Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [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, 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] 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] 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

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chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] 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] 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] 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] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [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] Orthostatic: Pertaining to or caused by standing erect. [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] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [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]

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Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] 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] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papilla: A small nipple-shaped elevation. [NIH] 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 Cells: Cells in the stomach wall that make hydrochloric acid. [NIH] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU]

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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] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroral: Performed through or administered through the mouth. [EU] 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] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top

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of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] 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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] 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] 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

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that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [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] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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]

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Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [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] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] 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

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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] Prosthesis: An artificial replacement of a part of the body. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] 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] 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] Proximate cause: The abnormal event in a causal chain lying closest to an accidental event. [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] Psychophysiology: The study of the physiological basis of human and animal behavior. [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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH]

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Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrosis: Heartburn. [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 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] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [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

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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]

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] 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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU]

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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] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

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] Reoperation: A repeat operation for the same condition in the same patient. It includes reoperation for reexamination, reoperation for disease progression or recurrence, or reoperation following operative failure. [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] 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] Retrosternal: Situated or occurring behind the sternum. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [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]

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Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Self Medication: The self administration of medication not prescribed by a physician or in a manner not directed by a physician. [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] Sepsis: The presence of bacteria in the bloodstream. [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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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]

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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] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [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] 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] Somnolence: Sleepiness; also unnatural drowsiness. [EU] 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

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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] Spectroscopic: The recognition of elements through their emission spectra. [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] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] 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 cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Stabilization: The creation of a stable state. [EU] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sternum: Breast bone. [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

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the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] 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] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [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] Supraspinal: Above the spinal column or any spine. [NIH] Surgical Instruments: Hand-held tools or implements used by health professionals for the performance of surgical tasks. [NIH] 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] 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

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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] Systemic disease: Disease that affects the whole body. [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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Tips to control heartburn: Avoid lying down 2 to 3 hours after eating. [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] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH]

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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] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [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] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] 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

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condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [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]

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] Urea Breath Test: A test used to detect Helicobacter pylori infection. The test measures breath samples for urease, an enzyme H. pylori makes. [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]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some

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viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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 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] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [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

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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] Zygote: The fertilized ovum. [NIH]

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INDEX A Abdomen, 113, 178, 199, 205, 206, 209, 217, 226, 227, 228, 235, 236, 246, 248 Abdominal, 18, 24, 29, 74, 120, 122, 130, 142, 179, 199, 214, 227, 235, 236, 250 Abdominal Pain, 122, 199, 227, 250 Ablate, 35, 199 Ablation, 5, 14, 35, 199 Acceptor, 199, 234, 247, 248, 249 Acetylcholine, 37, 199, 209, 233 Acetyltransferases, 128, 199 Achlorhydria, 120, 199 Acidity, 21, 35, 67, 103, 135, 199 Actin, 30, 199, 232 Adenosine, 199, 206, 224, 237 Adhesions, 19, 199 Adjustment, 136, 199 Adjuvant, 199, 201 Adrenergic, 199, 215, 217, 241 Adverse Effect, 130, 199, 245 Aerophagia, 114, 199 Affinity, 200, 228, 245 Age of Onset, 41, 200 Agglutinins, 196, 200 Aggressiveness, 32, 200 Agonist, 200, 204, 215 Airway, 12, 29, 85, 141, 200, 245, 251 Aldehyde Dehydrogenase, 128, 200 Aldehydes, 200, 251 Alendronate, 20, 200 Alertness, 200, 206 Algorithms, 20, 24, 200, 205 Alkaline, 13, 118, 200, 201, 204, 206 Alkaloid, 200, 241, 243 Alpha Particles, 200, 241 Alpha-helix, 200, 227 Alternative medicine, 93, 100, 154, 200 Aluminum, 103, 119, 120, 201 Aluminum Hydroxide, 103, 119, 120, 201 Ambulatory Care, 201 Ameliorating, 36, 201 Amine, 201, 223 Amino acid, 201, 202, 203, 221, 223, 228, 229, 236, 237, 238, 239, 240, 244, 247, 249, 250 Amino Acid Sequence, 201, 202 Aminolevulinic Acid, 13, 14, 201 Ammonia, 201, 250

Ampulla, 201, 216 Anaesthesia, 98, 201, 225 Anal, 112, 201, 217 Analgesic, 201, 241 Analog, 201, 219, 234 Anaplasia, 201 Anastomosis, 25, 201, 219 Anatomical, 16, 24, 29, 42, 180, 201, 209, 216, 225, 244 Anemia, 22, 177, 201 Anesthesia, 97, 98, 200, 201 Angina, 121, 122, 202 Angina Pectoris, 121, 122, 202 Animal model, 25, 33, 202 Anomalies, 202, 232 Antagonism, 202, 206 Antibacterial, 202, 246 Antibiotic, 21, 202, 246 Antibodies, 131, 200, 202, 224, 229, 231, 238 Antibody, 28, 200, 202, 210, 217, 223, 224, 225, 227, 229, 231, 241, 242, 246, 252 Anticholinergics, 20, 202 Antiemetic, 202, 230 Antigen, 53, 200, 202, 210, 213, 223, 224, 225, 229 Antigen-presenting cell, 202, 213 Anti-infective, 36, 202 Anti-inflammatory, 202, 203 Anti-Inflammatory Agents, 202, 203 Antipyretic, 202, 241 Antrectomy, 86, 203 Anus, 201, 203, 206, 210 Anxiety, 203, 235 Apnea, 47, 138, 194, 203 Apoptosis, 33, 39, 203 Arachidonic Acid, 203, 240 Arginase, 33, 203 Arginine, 33, 203, 233, 249 Arterial, 30, 203, 224, 240 Arteries, 203, 205, 212, 230, 232 Artery, 203, 212, 241 Aspiration, 12, 29, 97, 98, 121, 122, 124, 203 Aspirin, 113, 116, 158, 203 Asymptomatic, 10, 31, 124, 203, 235 Atresia, 145, 203 Atrophy, 9, 203

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Atypical, 16, 21, 45, 71, 142, 147, 174, 203 Autodigestion, 203, 235 Autonomic, 52, 199, 203, 233, 236 Axons, 203, 236 B Babesiosis, 203, 241 Baclofen, 79, 204 Bacteria, 202, 204, 211, 218, 219, 221, 222, 230, 244, 246, 249, 250 Bactericidal, 36, 204 Bacteriophage, 204, 249, 250 Bacterium, 204, 210, 211 Barium, 15, 16, 74, 148, 150, 196, 204, 218 Barium swallow, 15, 196, 204, 218 Basal cells, 116, 204 Basophils, 204, 221, 228 Belching, 48, 176, 179, 194, 200, 204 Benign, 123, 125, 204, 221, 232, 242 Benzamides, 130, 204 Beta-Thromboglobulin, 204, 226 Bile, 5, 6, 7, 13, 25, 30, 33, 113, 116, 135, 204, 205, 212, 216, 219, 220, 222, 228, 247 Bile Acids, 7, 25, 204, 220, 247 Bile Acids and Salts, 204 Bile duct, 30, 204, 205, 216, 222 Bile Reflux, 5, 6, 7, 13, 33, 204 Biliary, 147, 205, 210, 214, 235 Biliary Tract, 205, 235 Bilirubin, 7, 33, 205 Biochemical, 39, 205, 244 Biopsy, 10, 24, 43, 86, 144, 196, 205, 236 Biopsy specimen, 86, 205 Biotechnology, 44, 154, 167, 205 Biotransformation, 205 Bladder, 205, 211, 219, 225, 250, 251 Bloating, 42, 142, 179, 194, 205, 220, 225, 227 Blood Coagulation, 205, 206 Blood Platelets, 205, 238, 244 Blood pressure, 130, 205, 224, 231, 238, 245 Blood vessel, 205, 207, 209, 216, 227, 230, 236, 245, 248, 250 Body Burden, 205, 228 Body Fluids, 205, 215, 245 Body Mass Index, 18, 205, 234 Bolus, 34, 124, 205 Bolus infusion, 205 Bone Marrow, 205, 224, 229, 231 Bowel, 197, 201, 206, 214, 225, 226, 234, 236, 247, 250 Bowel Movement, 206, 214, 247 Brachial, 206, 229

Brachial Plexus, 206, 229 Brachytherapy, 206, 226, 227, 241, 252 Bradykinin, 206, 233 Brain Stem, 29, 206 Brash, 121, 122, 206 Bronchi, 206, 217, 249 Bronchial, 206, 223 Bronchitis, 88, 206 C Caffeine, 19, 158, 180, 197, 206, 241 Calcium, 37, 38, 94, 119, 120, 126, 135, 206, 207, 210, 226 Calcium Carbonate, 119, 120, 126, 206 Calmodulin, 206, 226 Calpain, 138, 207 Capsules, 207, 215 Carbohydrate, 92, 99, 207, 221, 238 Carbon Dioxide, 207, 213, 243, 250 Carcinogenesis, 33, 207, 209 Carcinogenic, 207, 226, 239 Carcinogens, 207, 251 Carcinoma, 12, 17, 33, 38, 138, 207 Cardia, 46, 52, 66, 81, 98, 112, 120, 125, 137, 207 Cardiac, 15, 18, 20, 22, 27, 117, 123, 147, 206, 207, 209, 212, 217, 218, 219, 232, 241 Cardiomyopathy, 138, 207 Cardiovascular, 143, 207, 214, 244 Carpal Tunnel Syndrome, 138, 207 Case report, 50, 92, 99, 207, 209 Case series, 207, 209 Case-Control Studies, 28, 207, 217 Catecholamine, 207, 214, 236 Catheter, 34, 35, 137, 207, 216, 226 Catheterization, 207, 226 Causal, 33, 37, 43, 50, 208, 217, 240, 243 Causality, 15, 208 Caustic, 6, 208 Cell Adhesion, 115, 127, 208 Cell Cycle, 66, 208, 212 Cell Death, 203, 208, 232 Cell Division, 204, 208, 230, 237, 239 Cell membrane, 38, 208, 219, 226, 237 Cell proliferation, 39, 208 Cell Respiration, 208, 243 Central Nervous System, 138, 199, 206, 208, 219, 221, 238, 244 Centrifugation, 208, 230 Cerebral, 29, 206, 208, 217, 218, 235, 246 Cerebral hemispheres, 206, 208 Cerebrum, 208 Cervical, 206, 208, 229

255

Character, 202, 208, 213 Chemoembolization, 30, 208 Chemoprevention, 44, 209 Chemopreventive, 40, 209 Chemotherapy, 145, 198, 209, 232 Chest Pain, 6, 14, 15, 22, 27, 57, 117, 120, 123, 138, 142, 147, 150, 176, 209, 218 Chest wall, 209, 238 Chin, 47, 209, 230 Cholecystectomy, 18, 29, 209 Cholesterol, 102, 204, 209 Cholinergic, 37, 209 Chromatin, 203, 209, 233 Chromosomal, 32, 209 Chromosome, 36, 209, 211, 228 Cinchona, 209, 241 Cirrhosis, 209, 222, 238 Clinical Medicine, 209, 239 Clinical series, 92, 209 Clinical study, 82, 209, 212 Clinical trial, 23, 24, 26, 29, 34, 41, 73, 167, 209, 212, 215, 232, 235, 240, 242 Cloning, 205, 209 Coenzyme, 199, 209 Cofactor, 210, 240 Cohort Studies, 13, 210, 217 Colitis, 210, 227 Collagen, 112, 201, 210, 218, 238, 239 Collapse, 124, 210, 238, 245 Colon, 102, 210, 225, 227, 228, 245, 249 Colorectal, 10, 11, 69, 210 Colorectal Cancer, 10, 11, 210 Common Bile Duct, 29, 210, 212, 222 Comorbidity, 41, 210 Competency, 121, 122, 210 Complement, 210, 211, 229 Complementary and alternative medicine, 97, 109, 211 Complementary medicine, 97, 211 Compliance, 24, 42, 52, 211 Computational Biology, 167, 211 Congenita, 211, 241 Congestion, 135, 211 Congestive heart failure, 138, 211 Conjugated, 204, 211, 213, 221 Conjugation, 128, 205, 211, 247 Connective Tissue, 206, 210, 211, 218, 219, 230, 236 Consciousness, 201, 211, 213, 240 Constipation, 38, 129, 211, 227 Constitutional, 212, 232 Constriction, 212, 227, 251

Consultation, 20, 26, 212 Contraindications, ii, 212 Control group, 24, 212 Controlled clinical trial, 29, 41, 212 Corneum, 212, 217, 224 Coronary, 22, 202, 212, 230, 232 Coronary Circulation, 202, 212 Coronary Disease, 22, 212 Coronary Thrombosis, 212, 230, 232 Coronary Vessels, 212 Corpus, 9, 22, 212 Cortex, 212, 218 Cortical, 29, 212, 218 Cranial, 212, 221, 236 Cross-Sectional Studies, 41, 212, 217 Curative, 42, 122, 212, 248 Cutaneous, 14, 212, 237 Cyanosis, 212, 217 Cyclic, 206, 207, 212, 221, 233 Cyclin, 39, 212 Cystic Duct, 210, 212, 222 Cytochrome, 55, 127, 213 Cytokine, 213, 226 Cytomegalovirus, 213, 219 Cytomegalovirus Infections, 213, 219 Cytoplasm, 203, 204, 208, 213, 216, 221, 226, 231, 232, 233 Cytoskeletal Proteins, 207, 213 Cytoskeleton, 30, 213 D Deamination, 213, 250 Decarboxylation, 213, 223 Degenerative, 213, 222 Deletion, 33, 203, 213 Delivery of Health Care, 213, 221 Dementia, 138, 213 Dendrites, 213, 233 Dendritic, 36, 213 Dendritic cell, 36, 213 Density, 205, 208, 214 Dentifrices, 201, 214 Deprivation, 138, 214 Dermal, 116, 214 Deuterium, 214, 223 Diabetes Mellitus, 101, 214, 222, 234 Diagnostic procedure, 15, 111, 150, 155, 183, 214 Diaphragm, 16, 114, 214, 223 Diarrhea, 38, 60, 129, 130, 214, 227 Dicyclomine, 202, 214 Diffusion, 214, 225

256

Gastroesophageal Reflux Disease

Digestion, 52, 126, 129, 134, 138, 180, 204, 206, 214, 215, 220, 225, 226, 228, 235, 246 Digestive system, 214, 220, 231 Digestive tract, 204, 214, 245, 246 Dihydrotestosterone, 214, 242 Dilation, 5, 146, 180, 206, 214 Direct, iii, 7, 12, 30, 33, 40, 113, 116, 157, 209, 214, 215, 241, 242, 247 Distal, 16, 57, 67, 81, 114, 124, 137, 138, 214, 220 Distention, 20, 113, 116, 214 Diuresis, 206, 214 Diverticulum, 47, 214 Dopamine, 214, 230, 233, 237 Dosage Forms, 77, 119, 215 Dosimetry, 14, 215 Double-blind, 75, 215 Drug Interactions, 5, 160, 177, 215 Duct, 201, 207, 210, 215, 216, 218, 243, 246 Duodenal Ulcer, 22, 31, 134, 142, 215, 233 Duodenogastric Reflux, 7, 215 Duodenum, 7, 134, 204, 215, 216, 219, 220, 227, 235, 236, 247 Dyes, 204, 215, 219, 233 Dyspepsia, 15, 20, 21, 26, 48, 121, 122, 126, 131, 132, 135, 142, 178, 215, 225 Dysphagia, 17, 22, 42, 76, 101, 116, 125, 145, 147, 194, 215 Dysplasia, 5, 6, 9, 12, 13, 14, 17, 25, 26, 28, 33, 35, 43, 144, 152, 215 Dyspnea, 215, 217 E Effector, 128, 199, 210, 215 Efficacy, 5, 9, 17, 30, 42, 45, 50, 55, 68, 82, 98, 99, 131, 215, 249 Elastin, 210, 215 Electrolyte, 215, 238, 245, 250 Electrons, 215, 227, 234, 241, 242 Embryo, 215, 225 Empiric, 12, 20, 215 Enamel, 216, 227 Endocrine Glands, 216 Endogenous, 33, 207, 214, 216, 249 Endorphins, 216, 233 Endoscope, 31, 56, 133, 136, 216 Endoscopic, 5, 7, 9, 11, 12, 14, 22, 24, 27, 29, 35, 41, 42, 45, 49, 51, 56, 59, 64, 73, 85, 114, 115, 119, 124, 125, 128, 136, 156, 183, 216, 218, 245 Endoscopic retrograde cholangiopancreatography, 30, 216 Endothelial cell, 216, 226

Endothelium, 216, 233 Endothelium-derived, 216, 233 Enkephalins, 216, 233 Enteropeptidase, 216, 249 Environmental Health, 166, 168, 216 Enzymatic, 115, 127, 201, 206, 211, 216, 223 Enzyme, 33, 131, 134, 200, 203, 210, 215, 216, 221, 227, 235, 237, 242, 248, 249, 250, 251 Eosinophil, 36, 216 Eosinophilic, 10, 36, 92, 216 Epidemic, 21, 27, 216 Epidemiologic Studies, 32, 217 Epidemiological, 21, 67, 217 Epidermal, 118, 119, 217, 227 Epidermal Growth Factor, 118, 119, 217 Epidermis, 204, 212, 217, 224, 227 Epidermoid carcinoma, 217, 246 Epigastric, 217, 235 Epinephrine, 199, 214, 217, 233 Epithelial, 26, 30, 33, 36, 119, 199, 217, 221, 222 Epithelial Cells, 36, 217, 222 Epithelium, 5, 10, 14, 20, 22, 26, 28, 35, 36, 39, 43, 115, 116, 124, 127, 133, 144, 216, 217, 219 Epitope, 30, 217 Eructation, 206, 217 Erythrocytes, 201, 203, 205, 207, 217 Esophageal Atresia, 145, 217, 249 Esophageal Manometry, 7, 12, 15, 21, 38, 82, 148, 151, 177, 179, 181, 217 Esophageal Perforation, 19, 217 Esophageal Stricture, 8, 13, 116, 124, 128, 132, 143, 217 Esophageal Ulcer, 6, 7, 115, 116, 117, 124, 127, 132, 138, 218 Esophagectomy, 35, 218 Esophagoscopy, 15, 218 Esophagram, 74, 204, 218 Evacuation, 135, 211, 218, 219 Evoke, 218, 246 Excitability, 218, 241 Excitation, 37, 38, 218, 233 Excitatory, 37, 204, 218, 220, 221 Exocrine, 218, 235 Exogenous, 205, 216, 218, 247 Expiration, 218, 243 External-beam radiation, 218, 227, 241, 251 Extracellular, 211, 218, 245 Extremity, 206, 218, 229

257

F Family Planning, 167, 218 Famotidine, 58, 59, 100, 105, 113, 116, 119, 156, 218 Fat, 19, 20, 28, 92, 129, 197, 203, 204, 205, 218, 228, 234 Fatigue, 144, 218, 222 Feces, 211, 218, 247 Fibroblasts, 218, 226 Fibrosis, 16, 145, 218, 244 Fistula, 218, 220, 234 Flatus, 219 Fluoroscopy, 42, 219 Fold, 17, 35, 219 Food and Beverages, 20, 219 Food Coloring Agents, 135, 219 Forearm, 205, 219, 229 Fundus, 20, 120, 124, 125, 133, 219 Fungi, 211, 219, 230, 250, 252 G Gallbladder, 18, 199, 205, 209, 212, 214, 216, 219, 220 Ganciclovir, 43, 219 Ganglia, 199, 219, 232, 236 Gap Junctions, 219, 248 Gas, 25, 46, 124, 130, 158, 199, 201, 204, 207, 214, 217, 219, 223, 225, 226, 227, 233, 238, 250 Gastrectomy, 57, 219 Gastric Bypass, 69, 219 Gastric Emptying, 8, 20, 23, 53, 112, 118, 145, 183, 219, 220 Gastric Fundus, 7, 113, 120, 124, 125, 219 Gastric Juices, 151, 177, 219, 235 Gastric Mucosa, 9, 119, 142, 144, 219 Gastrin, 11, 131, 219, 223 Gastritis, 9, 15, 27, 50, 64, 101, 102, 220 Gastroduodenal, 33, 220 Gastroenterologist, 42, 150, 220 Gastrointestinal tract, 10, 24, 34, 118, 138, 147, 220, 227, 244, 245 Gastroparesis, 13, 220 Gastroplasty, 92, 220 Gene, 28, 31, 32, 33, 36, 41, 44, 205, 220, 249 Gene Expression, 33, 44, 220 Genetics, 26, 211, 220 Genotype, 220, 237 Geriatric, 10, 49, 220 Gland, 220, 235, 244, 246, 247 Globus Sensation, 147, 220 Glottis, 220, 223

Glucose, 214, 220, 222, 226, 237 Glutamate, 135, 220, 221 Glutamic Acid, 221, 233, 239 Glycine, 201, 204, 221, 233, 244 Glycoproteins, 221, 227 Goblet Cells, 43, 221 Governing Board, 221, 239 Grade, 8, 12, 14, 17, 25, 145, 221 Grafting, 221, 225 Gram-negative, 221, 222 Granule, 36, 221 Granulocytes, 116, 221, 228, 251 Granuloma, 38, 221 Gravis, 138, 221 Guanylate Cyclase, 221, 233 H Halitosis, 12, 221 Haplotypes, 32, 221 Headache, 103, 206, 221 Health Care Costs, 29, 221 Health Expenditures, 221 Health Promotion, 150, 221 Health Services, iv, 23, 27, 92, 168, 213, 222 Health Status, 28, 41, 222 Heart attack, 143, 222 Heart failure, 138, 222 Heme, 201, 205, 213, 222 Hemochromatosis, 28, 222 Hemodialysis, 206, 222 Hemoglobin, 201, 212, 217, 222, 228 Hemorrhage, 26, 121, 122, 221, 222 Hemostasis, 222, 244 Hepatic, 210, 216, 222 Hepatic Duct, Common, 216, 222 Hepatitis, 87, 222 Hepatocellular, 30, 222 Hepatocellular carcinoma, 30, 222 Hepatocytes, 222 Heredity, 220, 223 Hernia, 8, 11, 16, 25, 65, 70, 77, 81, 114, 135, 145, 181, 183, 194, 223 Herpes, 194, 223 Herpes Zoster, 223 Heterogeneity, 32, 39, 200, 223 Hiatal Hernia, 8, 10, 11, 16, 24, 113, 125, 128, 145, 151, 154, 172, 179, 223 Hiccup, 67, 223 Histamine, 20, 33, 81, 119, 120, 159, 218, 223, 233, 242 Histidine, 223 Histology, 10, 35, 223

258

Gastroesophageal Reflux Disease

Hoarseness, 12, 19, 38, 129, 150, 155, 177, 195, 223, 228 Homeostasis, 38, 223 Homologous, 223, 247 Hormonal, 26, 203, 223 Hormone, 217, 219, 223, 232, 234, 245, 248 Hydrochloric Acid, 134, 199, 223, 235 Hydrogel, 121, 132, 223 Hydrogen, 25, 119, 134, 199, 201, 207, 214, 223, 231, 233, 234, 240 Hydrolysis, 203, 205, 223, 238, 249 Hydroxylysine, 210, 223 Hydroxyproline, 201, 210, 223 Hyperplasia, 116, 224 Hypersensitivity, 216, 224 Hypertension, 221, 224, 234, 238, 250 Hyperthermia, 224, 232 Hypertrophy, 224 Hypotension, 16, 224 Hypotensive, 24, 224 Hypothalamus, 224, 245 Hypoxanthine, 224, 251 Hypoxia, 138, 224 I Ichthyosis, 41, 224 Ileum, 224, 227, 251 Imidazole, 223, 224, 242 Immune response, 198, 199, 202, 224, 229, 247, 251 Immune Sera, 224 Immune system, 135, 202, 224, 225, 229, 251 Immunization, 131, 224, 225 Immunogenic, 131, 224 Immunoglobulin, 202, 224, 231 Immunologic, 224, 242 Immunotherapy, 225, 232 Impairment, 138, 145, 225 Implant radiation, 225, 226, 227, 241, 251 Implantation, 56, 84, 114, 121, 122, 132, 225 In situ, 122, 225 In vitro, 30, 39, 225, 248 In vivo, 35, 39, 225 Incision, 225, 226, 227 Incompetence, 220, 225 Incontinence, 115, 127, 214, 225 Indigestion, 120, 126, 129, 131, 143, 144, 150, 176, 184, 225, 227 Induction, 16, 98, 225 Infancy, 92, 225 Infantile, 47, 225

Infarction, 225 Infiltration, 116, 225 Inflammatory bowel disease, 11, 27, 41, 225 Ingestion, 6, 15, 113, 116, 120, 135, 221, 226, 238 Inhalation, 223, 226, 238 Initiation, 92, 99, 226, 249 Innervation, 206, 226, 229 Inorganic, 119, 226, 229, 231 Inositol, 38, 226 Inositol 1,4,5-Trisphosphate, 38, 226 Insecticides, 226, 251 Insight, 36, 39, 226 Insufflation, 42, 226 Interleukin-8, 56, 226 Intermittent, 67, 117, 121, 122, 132, 180, 226 Internal radiation, 226, 227, 241, 251 Interstitial, 206, 226, 227, 251 Intestinal, 9, 10, 22, 37, 38, 43, 52, 66, 67, 116, 144, 216, 222, 226, 232 Intestine, 37, 126, 202, 204, 206, 210, 226, 227, 236 Intoxication, 226, 251 Intracellular, 38, 206, 225, 226, 233, 238, 242 Intravenous, 77, 198, 226 Intrinsic, 16, 200, 226 Intubation, 50, 98, 208, 226 Invasive, 8, 14, 29, 34, 35, 74, 77, 83, 86, 120, 121, 122, 146, 226 Involuntary, 227, 232, 242, 245 Ion Channels, 38, 227, 248 Ions, 199, 206, 215, 223, 226, 227 Irradiation, 14, 227, 243, 252 Irritable Bowel Syndrome, 27, 37, 102, 227 Ischemia, 203, 227 J Jejunum, 219, 227 K Kb, 166, 227 Keratin, 43, 227 Keratinocytes, 226, 227 Kinetic, 227 L Lactose Intolerance, 135, 227 Laparoscopy, 29, 49, 58, 98, 227 Laparotomy, 19, 227 Large Intestine, 210, 214, 226, 227, 242, 245 Laryngeal, 29, 37, 50, 70, 228 Laryngeal Diseases, 29, 228

259

Laryngeal Mucosa, 38, 228 Laryngitis, 6, 37, 70, 228 Larynx, 123, 220, 228, 249, 251 Lead Poisoning, 98, 228 Lesion, 6, 17, 27, 28, 41, 134, 145, 221, 228, 249 Lethal, 19, 27, 204, 228 Leucine, 228, 235 Leucocyte, 216, 228 Leukocytes, 36, 204, 205, 221, 228, 231, 233 Ligaments, 212, 228 Ligands, 138, 228 Linkage, 21, 31, 32, 228 Lipophilic, 127, 228 Liver, 127, 138, 147, 199, 203, 204, 205, 207, 209, 213, 214, 218, 219, 220, 222, 228, 238, 250 Lobe, 124, 228 Localization, 14, 29, 228 Localized, 128, 137, 225, 228, 237, 244, 249 Longitudinal Studies, 212, 228 Loop, 219, 223, 228 Lymphatic, 216, 225, 229, 230, 238, 248 Lymphocyte, 202, 229 Lymphoid, 202, 228, 229 Lysine, 223, 229, 249 Lytic, 229, 250 M Magnesium Hydroxide, 119, 120, 229 Maintenance therapy, 4, 9, 13, 76, 229 Major Histocompatibility Complex, 221, 229 Malignancy, 22, 26, 28, 229 Malignant, 23, 26, 27, 117, 143, 199, 229, 232, 242 Malignant tumor, 117, 229 Malnutrition, 203, 229 Manifest, 10, 147, 229 Manometry, 42, 82, 172, 196, 229 Mastication, 118, 229 Medial, 123, 229 Median Nerve, 138, 207, 229 Mediate, 30, 39, 215, 229, 242 Mediator, 229, 238, 244 Medical Assistance, 156, 229 Medical Records, 229, 243 Medicament, 134, 135, 229 MEDLINE, 167, 230 Meiosis, 230, 247 Membrane, 38, 208, 211, 218, 221, 227, 228, 230, 231, 234, 236, 237, 238, 241 Memory, 122, 213, 230

Meninges, 208, 230 Mental, iv, 9, 23, 166, 168, 181, 209, 213, 218, 225, 230, 240, 244, 250 Mesenchymal, 217, 230 Meta-Analysis, 83, 230 Metaplasia, 9, 10, 12, 22, 39, 42, 43, 52, 66, 67, 132, 143, 144, 230 Metastasis, 230 Metastatic, 147, 230 Metoclopramide, 107, 130, 159, 181, 230 MI, 18, 120, 198, 230 Microbiology, 203, 230 Microorganism, 11, 210, 230, 251 Microsomal, 128, 230 Midaxillary line, 230, 251 Migration, 65, 230 Millimeter, 230, 251 Minority Groups, 7, 230 Mitosis, 203, 230 Mobility, 42, 231 Mobilization, 30, 231 Modeling, 27, 231 Modification, 17, 18, 114, 151, 176, 180, 201, 231, 241 Molecular, 30, 32, 33, 36, 39, 44, 86, 167, 169, 205, 206, 211, 231, 238, 242, 249 Molecule, 36, 202, 209, 210, 212, 215, 216, 217, 218, 223, 231, 234, 237, 238, 242, 250 Monitor, 174, 182, 231, 233 Monoclonal, 30, 227, 231, 241, 252 Monoclonal antibodies, 30, 231 Monocytes, 226, 228, 231 Mononuclear, 221, 231 Motility, 15, 26, 37, 38, 58, 66, 76, 80, 99, 130, 179, 183, 231, 244 Motion Sickness, 231, 232 Motor Activity, 113, 116, 231 Mucins, 221, 231, 243 Mucociliary, 231, 245 Mucosa, 5, 7, 8, 12, 14, 17, 20, 21, 22, 25, 33, 36, 39, 113, 116, 119, 121, 131, 132, 135, 144, 219, 231 Mucositis, 231, 248 Mucus, 119, 231, 250 Multicenter Studies, 31, 231 Multicenter study, 41, 82, 232 Muscle Contraction, 38, 232 Myasthenia, 138, 232 Mydriatic, 214, 232 Myenteric, 37, 232 Myocardial infarction, 121, 122, 204, 212, 230, 232

260

Gastroesophageal Reflux Disease

Myocardial Ischemia, 202, 212, 232 Myocardium, 202, 230, 232 Myofibrils, 207, 232 Myosin, 232 Myotonia, 232, 241 N Nausea, 14, 19, 129, 135, 155, 195, 202, 215, 220, 225, 232, 250 Necrosis, 203, 225, 230, 232 Neoadjuvant Therapy, 146, 232 Neoplasia, 232 Neoplasm, 232 Neoplastic, 39, 201, 232 Nerve, 37, 199, 201, 203, 206, 209, 213, 220, 226, 229, 232, 233, 238, 244, 246, 249 Nervous System, 208, 229, 232, 233, 236, 248 Neural, 16, 233 Neurologic, 87, 138, 145, 233 Neuromuscular, 199, 233, 250 Neuromuscular Junction, 199, 233 Neuronal, 130, 233, 236 Neurons, 37, 213, 218, 219, 233, 247 Neuropathy, 138, 233 Neuropeptides, 207, 233 Neurotransmitter, 130, 199, 201, 206, 214, 220, 221, 223, 227, 233, 245, 247 Neutralization, 120, 233 Neutrons, 200, 227, 233, 241 Neutrophils, 221, 226, 228, 233 Nitric Oxide, 33, 233 Nizatidine, 75, 107, 119, 156, 233 Norepinephrine, 199, 214, 233 Nuclear, 56, 211, 215, 232, 233 Nuclei, 29, 200, 211, 215, 230, 233, 240 Nucleus, 203, 204, 209, 212, 213, 214, 230, 231, 233, 234, 239, 240 Nurse Practitioners, 17, 234 O Occult, 43, 48, 234 Octreotide, 138, 234 Odynophagia, 22, 116, 121, 122, 147, 234 Oesophagitis, 6, 11, 21, 99, 234 Office Management, 148, 234 Ointments, 215, 234 Omeprazole, 4, 5, 9, 13, 45, 63, 76, 79, 83, 92, 107, 156, 159, 175, 181, 234, 240 Oral Hygiene, 221, 234 Oral Manifestations, 142, 234 Organ Culture, 234, 248 Orthostatic, 234 Osteoporosis, 102, 200, 234

Otolaryngology, 43, 62, 78, 234 Outpatient, 234 Overweight, 92, 93, 126, 178, 195, 234 Oxidation, 128, 199, 205, 213, 234 Oxygen Consumption, 234, 243 P Palliative, 235, 248 Pancreas, 147, 199, 204, 214, 220, 222, 235, 245, 249 Pancreatic, 135, 216, 220, 235 Pancreatic Ducts, 216, 235 Pancreatic Juice, 135, 220, 235 Pancreatitis, 19, 235 Panic, 15, 235 Papilla, 216, 235 Parietal, 30, 234, 235, 236 Parietal Cells, 30, 235 Parietal Lobe, 235 Paroxysmal, 202, 235 Particle, 235, 249 Pathogenesis, 16, 24, 26, 28, 32, 43, 78, 143, 235 Pathologic, 16, 145, 203, 205, 212, 224, 235 Pathologic Processes, 203, 235 Pathophysiology, 15, 16, 19, 27, 29, 42, 49, 57, 67, 143, 147, 148, 183, 235 Patient Education, 151, 173, 174, 180, 181, 182, 188, 190, 198, 235 Patient Selection, 14, 235 Pelvis, 199, 235, 250 Pepsin, 116, 120, 133, 134, 135, 235 Pepsin A, 134, 235 Peptic, 4, 8, 10, 12, 15, 26, 39, 45, 88, 113, 116, 119, 132, 134, 142, 147, 178, 194, 235, 236 Peptic Ulcer, 15, 45, 88, 119, 134, 142, 147, 178, 236 Peptide, 201, 216, 227, 235, 236, 238, 240 Percutaneous, 49, 58, 120, 236 Perforation, 19, 120, 128, 236 Perfusion, 224, 236 Peripheral Nerves, 138, 236, 246 Peripheral Nervous System, 216, 233, 236, 245, 247 Peristalsis, 36, 70, 118, 236 Peritoneal, 147, 236 Peritoneum, 236 Peroral, 122, 236 Pharmaceutical Solutions, 215, 236 Pharmacists, 65, 150, 236 Pharmacodynamic, 218, 236 Pharmacokinetic, 236

261

Pharmacologic, 17, 143, 202, 236, 249 Pharmacotherapy, 51, 63, 183, 236 Pharynx, 122, 123, 220, 236 Phenotype, 43, 237 Phenylalanine, 108, 235, 237 Phospholipids, 218, 226, 237 Phosphorus, 206, 237 Phosphorylase, 207, 237 Phosphorylation, 30, 237 Photoallergy, 237 Photodynamic therapy, 5, 14, 237 Photosensitivity, 14, 237 Photosensitizer, 14, 237 Physical Examination, 182, 237 Physiologic, 12, 16, 27, 38, 112, 113, 123, 133, 143, 200, 237, 242 Physiology, 24, 26, 29, 30, 42, 126, 142, 150, 176, 181, 220, 237 Pigment, 205, 237 Pilot study, 32, 43, 237 Plants, 200, 207, 220, 233, 237, 249 Plasma, 30, 202, 204, 208, 222, 237, 238 Plasma cells, 202, 238 Platelet Aggregation, 233, 238 Platelet Factor 4, 226, 238 Platelets, 204, 207, 233, 238 Pleated, 227, 238 Plexus, 37, 206, 238 Pneumonia, 212, 238 Pneumothorax, 19, 238 Poisoning, 226, 232, 238 Polypeptide, 201, 210, 217, 235, 238, 245 Polyposis, 27, 41, 210, 238 Polysaccharide, 202, 238 Pons, 206, 238 Portal Hypertension, 217, 238 Posterior, 201, 230, 235, 238 Postmenopausal, 200, 234, 238 Postoperative, 8, 42, 146, 180, 238 Postprandial, 16, 20, 59, 238 Postsynaptic, 238, 248 Potassium, 20, 238, 241 Practicability, 239, 249 Practice Guidelines, 168, 183, 239 Precancerous, 12, 15, 19, 145, 155, 209, 239 Precipitating Factors, 208, 239 Precursor, 6, 28, 32, 41, 145, 203, 214, 215, 216, 233, 237, 239, 249 Premalignant, 10, 17, 22, 31, 35, 239 Presynaptic, 37, 233, 239, 247 Prevalence, 7, 10, 16, 21, 31, 32, 35, 40, 41, 43, 70, 114, 117, 145, 151, 239

Preventive Medicine, 11, 189, 239 Probe, 24, 35, 87, 239 Progeny, 211, 239 Progression, 6, 12, 13, 14, 33, 39, 43, 51, 128, 143, 146, 154, 202, 239, 243 Progressive, 209, 213, 232, 239 Prokinetic Drugs, 145, 150, 239 Proline, 210, 223, 239 Promoter, 36, 43, 115, 127, 239 Prone, 135, 151, 183, 239 Prone Position, 151, 239 Prophase, 239, 247 Prospective Studies, 55, 239 Prospective study, 41, 240 Prostaglandins, 33, 203, 240 Prosthesis, 113, 122, 132, 240 Protein C, 201, 204, 227, 240, 250 Protein S, 26, 205, 240 Proteins, 30, 39, 135, 201, 202, 207, 208, 209, 210, 219, 227, 231, 232, 235, 236, 237, 240, 242, 244, 247, 249, 250 Protocol, 18, 41, 240 Protons, 200, 223, 240, 241 Protozoa, 211, 230, 240, 250 Proximate cause, 133, 240 Psychic, 230, 240 Psychoactive, 240, 251 Psychophysiology, 27, 240 Public Assistance, 229, 240 Public Policy, 167, 240 Publishing, 6, 7, 8, 10, 11, 13, 15, 16, 17, 20, 44, 142, 240 Pulmonary, 116, 120, 121, 122, 123, 124, 138, 195, 205, 216, 240, 241 Pulmonary Artery, 205, 241 Pulse, 231, 241 Pupil, 214, 232, 241 Purines, 241, 244, 251 Pyrosis, 113, 116, 135, 241 Q Quality of Life, 6, 11, 12, 18, 27, 28, 34, 40, 54, 63, 66, 73, 80, 84, 181, 241 Quinidine, 20, 159, 209, 241 Quinine, 128, 209, 241 R Race, 230, 241 Radiation, 34, 113, 116, 202, 218, 224, 226, 227, 232, 241, 242, 251 Radiation therapy, 218, 226, 227, 232, 241, 252 Radioactive, 205, 223, 225, 226, 227, 231, 233, 241, 252

262

Gastroesophageal Reflux Disease

Radiofrequency ablation, 30, 86, 241 Radiography, 16, 241 Radiolabeled, 227, 241, 252 Radiological, 29, 236, 241 Radiology, 241 Radionuclide Imaging, 86, 242 Radiotherapy, 206, 227, 241, 242, 252 Randomized, 5, 8, 29, 34, 41, 63, 71, 75, 215, 242 Randomized clinical trial, 34, 63, 242 Ranitidine, 4, 5, 48, 52, 63, 92, 108, 119, 120, 156, 242 Reagent, 223, 242 Receptor, 4, 9, 20, 21, 26, 33, 37, 38, 81, 119, 120, 129, 138, 145, 150, 151, 159, 180, 202, 215, 218, 233, 242, 244 Receptors, Serotonin, 242, 244 Recombinant, 242, 250 Recombination, 211, 242 Rectum, 203, 206, 210, 214, 219, 225, 227, 242 Recur, 8, 12, 118, 242 Recurrence, 21, 99, 146, 209, 242, 243 Reductase, 128, 242 Refer, 1, 210, 216, 219, 223, 228, 233, 242, 249 Reflex, 29, 81, 242 Refraction, 242, 246 Refractory, 9, 33, 242 Regeneration, 39, 243 Regimen, 5, 9, 20, 35, 38, 215, 236, 243 Relapse, 4, 9, 63, 243 Reliability, 12, 243 Remission, 229, 242, 243 Reoperation, 77, 243 Repopulation, 14, 243 Resected, 24, 35, 243 Resection, 13, 146, 243 Respiration, 16, 203, 207, 231, 243 Retrograde, 243 Retrospective, 41, 42, 55, 87, 243 Retrospective Studies, 42, 243 Retrospective study, 41, 243 Retrosternal, 131, 243 Risk factor, 6, 11, 14, 18, 19, 28, 32, 39, 41, 43, 82, 116, 147, 150, 208, 217, 240, 243 Ryanodine, 38, 243 S Saliva, 12, 243, 244 Salivary, 118, 119, 213, 214, 243, 247 Salivary glands, 119, 213, 214, 243 Salivation, 217, 244

Schizoid, 244, 251 Schizophrenia, 102, 244, 251 Schizotypal Personality Disorder, 244, 251 Scleroderma, 13, 21, 102, 244 Scleroproteins, 227, 244 Sclerosis, 138, 244 Screening, 3, 10, 12, 20, 24, 27, 31, 42, 65, 173, 180, 209, 244 Secretory, 27, 234, 244, 247 Self Administration, 244 Self Medication, 4, 244 Sensibility, 135, 201, 244 Sepsis, 19, 244 Serine, 244, 249 Serotonin, 130, 233, 236, 242, 244, 249 Serous, 46, 216, 244 Serum, 28, 210, 224, 244 Shock, 19, 244, 249 Side effect, 22, 126, 129, 156, 157, 161, 199, 245, 248 Sigmoid, 245 Sigmoidoscopy, 10, 245 Signs and Symptoms, 70, 146, 243, 245, 250 Sinusitis, 12, 102, 245 Skeletal, 16, 121, 232, 241, 245 Skeleton, 199, 245 Skull, 245, 248 Sleep apnea, 50, 138, 245 Small intestine, 7, 132, 134, 212, 215, 216, 223, 224, 226, 227, 245, 249 Smoking Cessation, 177, 245 Smooth muscle, 16, 38, 112, 206, 207, 223, 245, 247 Social Environment, 241, 245 Sodium, 119, 120, 158, 159, 241, 245 Sodium Bicarbonate, 119, 120, 158, 159, 245 Somatostatin, 138, 234, 245 Somnolence, 82, 245 Spasm, 99, 193, 223, 245 Spastic, 102, 227, 245 Specialist, 21, 185, 214, 246 Species, 217, 230, 231, 241, 246, 249, 251 Specificity, 14, 15, 200, 246 Spectroscopic, 24, 246 Spectrum, 16, 61, 92, 143, 246 Sperm, 209, 246 Sphincter, 8, 15, 16, 17, 20, 21, 24, 42, 52, 68, 86, 99, 112, 114, 116, 118, 120, 121, 122, 125, 128, 129, 132, 135, 137, 143,

263

145, 150, 155, 177, 178, 179, 183, 220, 228, 246 Spinal cord, 204, 206, 208, 209, 229, 230, 232, 233, 236, 242, 246 Spinal Nerves, 236, 246 Squamous, 5, 6, 14, 20, 26, 35, 36, 39, 43, 132, 133, 147, 217, 228, 246 Squamous cell carcinoma, 6, 217, 246 Squamous cells, 246 Squamous Epithelium, 5, 20, 26, 35, 36, 39, 43, 132, 133, 147, 228, 246 Stabilization, 35, 246 Stenosis, 246, 247 Sternum, 115, 120, 121, 122, 127, 243, 246 Stimulant, 158, 206, 223, 246 Stimulus, 30, 218, 226, 227, 242, 246, 248 Stool, 53, 176, 197, 210, 225, 227, 228, 247 Stress, 17, 28, 42, 126, 131, 179, 207, 220, 227, 232, 247 Stricture, 4, 9, 14, 117, 145, 147, 150, 152, 246, 247 Subacute, 225, 245, 247 Subclinical, 225, 247 Subcutaneous, 247, 251 Submaxillary, 217, 247 Substance P, 205, 244, 247 Sulfotransferases, 128, 247 Supine, 8, 85, 113, 116, 247 Supplementation, 25, 247 Suppression, 5, 9, 14, 35, 38, 45, 118, 183, 247 Suppressive, 38, 247 Supraspinal, 204, 247 Surgical Instruments, 128, 247 Survival Rate, 42, 247 Symptomatic, 4, 7, 17, 21, 31, 32, 49, 53, 54, 57, 58, 59, 67, 72, 80, 100, 118, 145, 175, 183, 198, 235, 247 Synapse, 199, 233, 239, 247, 249 Synaptic, 37, 233, 247 Synaptic Transmission, 37, 247 Systemic, 158, 159, 205, 217, 224, 225, 227, 241, 244, 245, 248, 249, 252 Systemic disease, 224, 248 T Temporal, 54, 83, 248 Testosterone, 242, 248 Therapeutics, 4, 11, 45, 55, 63, 160, 248 Thoracic, 48, 77, 128, 206, 214, 229, 248, 251 Thorax, 199, 248 Threshold, 34, 53, 218, 224, 248

Thrombosis, 204, 240, 248 Thymidine, 43, 248 Thymidine Kinase, 43, 248 Thymus, 224, 229, 248 Tips to control heartburn, 151, 248 Tissue Culture, 37, 248 Tomography, 10, 35, 248 Tone, 30, 112, 121, 122, 217, 234, 248 Tonus, 125, 248 Topical, 245, 248 Toxic, iv, 11, 119, 127, 209, 211, 233, 248, 249 Toxicity, 215, 233, 248 Toxicokinetics, 248 Toxicology, 37, 168, 249 Toxin, 33, 134, 249 Trachea, 206, 228, 237, 249 Tracheoesophageal Fistula, 217, 249 Transcription Factors, 39, 249 Transduction, 39, 226, 249 Transfection, 205, 249 Transfer Factor, 224, 249 Transferases, 128, 249 Transgenes, 43, 249 Transmitter, 37, 199, 214, 227, 229, 233, 249 Transplantation, 60, 71, 224, 229, 249 Trauma, 218, 221, 232, 235, 249 Treatment Outcome, 7, 249 Trypsin, 7, 25, 216, 249 Tryptophan, 210, 244, 249 Tunica, 231, 249 U Ulcer, 19, 21, 26, 120, 134, 135, 142, 144, 194, 197, 215, 218, 249 Ulceration, 150, 236, 249 Ulcerative colitis, 27, 41, 225, 249 Uraemia, 235, 250 Urea, 21, 203, 250 Urea Breath Test, 21, 250 Urease, 250 Urethra, 250 Urinary, 112, 115, 127, 214, 225, 250, 251 Urinate, 250, 251 Urine, 127, 197, 205, 214, 217, 225, 250 Uterus, 208, 212, 219, 250 V Vaccines, 201, 250, 251 Vascular, 138, 216, 225, 233, 250 Vasculitis, 235, 250 Vasodilator, 206, 215, 223, 250 VE, 11, 51, 250

264

Gastroesophageal Reflux Disease

Vector, 68, 249, 250 Vein, 226, 233, 238, 250 Venous, 204, 240, 250 Vesicular, 223, 230, 250 Veterinary Medicine, 167, 250 Viral, 87, 249, 250 Virulent, 28, 62, 250 Virus, 204, 249, 250 Visceral, 27, 236, 251 Vitamin A, 226, 251 Vitro, 251 Vivo, 35, 251 Vocal cord, 38, 116, 220, 251 Void, 39, 251 W Waist circumference, 28, 251

Wheezing, 19, 116, 121, 122, 135, 155, 177, 196, 251 White blood cell, 202, 228, 229, 231, 238, 251 Windpipe, 237, 251 Withdrawal, 118, 251 X Xanthine, 128, 251 Xanthine Oxidase, 128, 251 Xenobiotics, 127, 251 Xenograft, 202, 251 X-ray, 196, 204, 216, 218, 219, 227, 233, 241, 242, 251 X-ray therapy, 227, 251 Y Yeasts, 219, 237, 252 Z Zygote, 211, 252

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