Barrett's Esophagus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

BARRETT’S ESOPHAGUS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES ...

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BARRETT’S ESOPHAGUS 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., 1960Barrett’s Esophagus: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84349-X 1. Barrett’s Esophagus-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 Barrett’s esophagus. 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 BARRETT’S ESOPHAGUS ............................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Barrett’s Esophagus ...................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 39 The National Library of Medicine: PubMed ................................................................................ 40 CHAPTER 2. NUTRITION AND BARRETT’S ESOPHAGUS .................................................................. 85 Overview...................................................................................................................................... 85 Finding Nutrition Studies on Barrett’s Esophagus ..................................................................... 85 Federal Resources on Nutrition ................................................................................................... 87 Additional Web Resources ........................................................................................................... 88 CHAPTER 3. ALTERNATIVE MEDICINE AND BARRETT’S ESOPHAGUS ............................................ 89 Overview...................................................................................................................................... 89 National Center for Complementary and Alternative Medicine.................................................. 89 Additional Web Resources ........................................................................................................... 91 General References ....................................................................................................................... 91 CHAPTER 4. DISSERTATIONS ON BARRETT’S ESOPHAGUS .............................................................. 93 Overview...................................................................................................................................... 93 Dissertations on Barrett’s Esophagus.......................................................................................... 93 Keeping Current .......................................................................................................................... 94 CHAPTER 5. CLINICAL TRIALS AND BARRETT’S ESOPHAGUS ........................................................ 95 Overview...................................................................................................................................... 95 Recent Trials on Barrett’s Esophagus.......................................................................................... 95 Keeping Current on Clinical Trials ............................................................................................. 96 CHAPTER 6. PATENTS ON BARRETT’S ESOPHAGUS ........................................................................ 99 Overview...................................................................................................................................... 99 Patent Applications on Barrett’s Esophagus ............................................................................... 99 Keeping Current ........................................................................................................................ 100 CHAPTER 7. BOOKS ON BARRETT’S ESOPHAGUS .......................................................................... 101 Overview.................................................................................................................................... 101 Book Summaries: Federal Agencies............................................................................................ 101 Book Summaries: Online Booksellers......................................................................................... 102 Chapters on Barrett’s Esophagus............................................................................................... 102 CHAPTER 8. PERIODICALS AND NEWS ON BARRETT’S ESOPHAGUS ............................................ 105 Overview.................................................................................................................................... 105 News Services and Press Releases.............................................................................................. 105 Academic Periodicals covering Barrett’s Esophagus ................................................................. 108 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 111 Overview.................................................................................................................................... 111 U.S. Pharmacopeia..................................................................................................................... 111 Commercial Databases ............................................................................................................... 112 Researching Orphan Drugs ....................................................................................................... 112 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 117 Overview.................................................................................................................................... 117 NIH Guidelines.......................................................................................................................... 117 NIH Databases........................................................................................................................... 119 Other Commercial Databases..................................................................................................... 121 APPENDIX B. PATIENT RESOURCES ............................................................................................... 123 Overview.................................................................................................................................... 123 Patient Guideline Sources.......................................................................................................... 123

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Finding Associations.................................................................................................................. 126 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 129 Overview.................................................................................................................................... 129 Preparation................................................................................................................................. 129 Finding a Local Medical Library................................................................................................ 129 Medical Libraries in the U.S. and Canada ................................................................................. 129 ONLINE GLOSSARIES................................................................................................................ 135 Online Dictionary Directories ................................................................................................... 136 BARRETT’S ESOPHAGUS DICTIONARY.............................................................................. 137 INDEX .............................................................................................................................................. 177

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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 Barrett’s esophagus 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 Barrett’s esophagus, 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 Barrett’s esophagus, 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 Barrett’s esophagus. 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 Barrett’s esophagus, 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 Barrett’s esophagus. 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 BARRETT’S ESOPHAGUS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Barrett’s esophagus.

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

Screening and Surveillance for Barrett Esophagus in High-Risk Groups: A CostUtility Analysis Source: Annals of Internal Medicine. 138(3): 176-186. February 4, 2003. Summary: Once in a lifetime screening for Barrett esophagus has been proposed for patients with gastroesophageal reflux disease (GERD), but there is little evidence of its cost-effectiveness. This article reports on a study that designed a model to determine the cost effectiveness of screening high risk groups for Barrett esophagus and for providing surveillance to patients with Barrett esophagus; the model also compared the results with the cost-effectiveness of no screening or surveillance. Results determined that screening with surveillance limited to patients with Barrett esophagus with dysplasia required $10, 440 per quality adjust life year (QALY) saved compared to no screening or

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Barrett’s Esophagus

surveillance. The incremental cost-effectiveness ratio of surveillance every 5 years in patients with Barrett esophagus without dysplasia compared to those with dysplasia was $596,000 per QALY saved. The authors conclude that screening 50 year old men with symptoms of GERD to detect adenocarcinoma associated with Barrett esophagus is probably cost-effective. However, subsequent surveillance of patients with Barrett esophagus but no dysplasia, even at 5 year intervals, is an expensive practice. 2 figures. 4 tables. 63 references. •

Barrett's Esophagus Source: New England Journal of Medicine. NEJM. 346(11): 836-842. March 14, 2002. Summary: This article offers a case report of a man with Barrett's esophagus, followed by a discussion of the possible treatment and patient management strategies that could be employed in the case, including formal guidelines for the condition under discussion. The article ends with the author's clinical recommendations in the case. Topics include screening and surveillance for Barrett's esophagus, the treatment of gastroesophageal reflux disease (GERD) in patients with Barrett's esophagus, dysplasia, the natural history of high-grade dysplasia, and areas of uncertainty. The author concludes that endoscopic screening for Barrett's esophagus should be considered for patients who have chronic symptoms of GERD (i.e., symptoms that have lasted for more than 5 years). The group at highest risk for cancer consists of obese white men over the age of 50 years. 3 figures. 57 references.

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

Project Title: ESOSPHAGUS

A

NOVEL

TECHNIQUE

FOR

SCREENING

BARRETT'S

Principal Investigator & Institution: Wang, Kenneth K.; Associate Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 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).

Studies

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

•

Project Title: ADVANCED DIAGNOSTICS

MULTISPECTRAL

IMAGING

FOR

MEDICAL

Principal Investigator & Institution: Vo-Dinh, Tuan; Group Leader and Corporate Fellow; Ut-Battelle, Llc-Oak Ridge National Lab Oak Ridge, Tn 378316253 Timing: Fiscal Year 2002; Project Start 13-AUG-2001; Project End 31-JUL-2006 Summary: (Verbatim from Applicant's Abstract): This project will develop a novel multi-spectral imaging (MSI) system using the synchronous luminescence (SL) concept to rapidly detect cancer in vivo. The proposal will address the problem of real-time in

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vivo identification and characterization of malignant and pre-malignant tissues in the upper gastrointestinal tract. While presence of Barrett's mucosa is simple to detect endoscopically, at the present time dysplasia and early cancer is found by extensive biopsies. The typical protocol is four quadrant biopsies at 2-cm intervals of the Barrett's mucosa. While this is the standard technique, it only provides 3-5 percent sampling of the mucosal surface where dysplasia and diffuse cancer may be found. The remaining 97-95 percent of the mucosa is not sampled. Laser-induced fluorescence (LIF) spectroscopy has already been used to detect cancer and high grade dysplasia in Barrett's esophagus. However, that system uses a contact technique which samples a 1 mm area of tissue at each measurement. While the contact LIF system is better than the pinch biopsy technique, a new system is needed to allow examination of the entire surface of the mucosa. To address this important need in imaging, a real-time synchronous imaging system will be developed, based on state-of-the-art acousto-optic tunable filter technology coupled to an endoscope. Novel MSI imaging technology will be developed to obtain spatially resolved images of the slight differences in SL properties of malignant versus non-malignant tumors. Synchronous luminescence analysis will greatly simplify the resulting fluorescence from the tissue. This in turn will provide a faster and more accurate in vivo analysis without biopsy. The unique imaging aspect of this MSI system will provide real-time spatial information, allowing for comprehensive diagnosis of large areas of interest. Following development of this technology, initial studies will be performed on two model systems, biopsied tissues as well as laboratory animals at Oak Ridge National Laboratory (ORNL) and the University of Tennessee. Once the system has been optimized, clinical in vivo studies will be performed on human subjects at the Thompson Cancer Survival Center (TCSC) in Knoxville, Tennessee. An interdisciplinary approach will be used to perform the proposed research to provide results in an efficient and cost effective manner. Project personnel include an interdisciplinary group of researchers, uniquely available at ORNL, with experience in a wide range of technical areas: molecular spectroscopy and advanced instrumentation, molecular biology, cellular biology. microelectroptics and molecular genetics and mouse studies. In addition, project personnel include a veterinarian at the University of Tennessee, and medical researchers with expertise in clinical studies at the TCSC. 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

Studies

7

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 •

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 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

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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: BACTERIAL FLORA IN NORMAL ESOPHAGUS & REFLUX DISORDERS Principal Investigator & Institution: Pei, Zhiheng; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Gastroesophageal reflux (GERD) is a chronic inflammatory disease affecting millions of Americans leading to the development of gastric/intestinal metaplasia (Barrett's esophagus), which is a precursor for adenocarcinoma (Ca). Although data from the stomach and colon suggest that colonizing bacteria are essential in inflammation-induced cancer development, little is known about esophageal bacterial flora. The long-term goal of this project is to define the role of bacteria in the progression of GERD to Barrett's esophagus and Ca. Our hypothesis is that bacterial flora exist in the normal esophagus, changing in the evolution of GERD into Barrett's esophagus and Ca. The specific aims are to: 1) define at a population level the bacterial flora in the normal esophagus and the esophagus with GERD-related diseases, 2) define at a species level the bacterial flora in the normal esophagus and GERD-related diseases, 3) determine host humoral immune responses to esophageal bacteria in patients with GERD-related diseases and controls. To define bacterial flora at a population level. The total number of bacteria per biopsy will be determined by quantitative real-time PCR using universal bacterial 16S rDNA primers with DNA from each biopsy. Specimens from disease groups will be compared for bacterial density (square mm mucosa). To define the flora at a species level, biopsies will be analyzed using sequence-based universal bacterial16S PCR and cultivation. PCR products will be cloned and sequenced, and species identification accomplished by comparing the sequences with kno\\0'D bacterial 16S sequences. Biopsies also will be cultured in anaerobic, aerobic, and microaerobic conditions, and colonies biochemically defined to a species level. Each disease group will be compared for the species identified and their prevalence. Cultivable whole cell bacterial antigens will be used in ELISA to determine whether the hosts recognize their presence. Serum antibodies also will be examined using immonoblots to identify disease-specific antigens. Significance: (i) Bacterial flora in the GI tract play important roles in pathologic conditions including inflammation and neoplasia. The esophagus is the only part of the GI tract where little is known about the bacterial flora, and the proposed study will assess the existence and complexity of the flora. (ii) While GERD initially results from chemical damage, bacterial overgrowth may promote intestinal metaplasia of the esophagus. The proposed study allows qualitative and quantitative examination of this hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

9

Project Title: BARRETT'S ESOPHAGUS ABLATION WITH CELOCOXIB TRIAL Principal Investigator & Institution: Lightdale, Charles J.; Professor of Clinical Medicine; Comprehensive Cancer Center; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 20-JUL-2001; Project End 30-JUN-2003 Summary: We propose to conduct a prospective randomized controlled trial comparing the cyclooxygenase-2 (COX-2) inhibitor celecoxib, in combination with endoscopic thermal ablation of Barrett's esophagus, to placebo and thermal ablation. COX-2 is overexpressed in Barrett's metaplasia. In this double-blind trial, 20 patients will be randomized to celecoxib or placebo (ratio 1:1) immediately following ablation. Celecoxib will be administered orally; 200 mg twice per day; the dose schedule for the placebo will be the same. Thermal ablation of Barrett's metaplasia will be carried out during endoscopy using argon plasma coagulation. Medication will be continued for one year, at which time a second endoscopy will be carried out to assess the outcomes. Endoscopic mapping of the Barrett's areas will be carried out at baseline and at one year. Primary study outcomes will be the comparison of the area of recurrent Barrett's metaplasia after ablation in the patients receiving celecoxib versus those receiving placebo, and the comparison of adverse events in the two treatment groups. Secondary outcomes will include change from baseline for the following measures in tissue samples from the treated areas: COX-2 mRNA, p53, cyclin D-1, Ki-67, and TUNEL assay. Eligible individuals will have an established diagnosis of Barrett's metaplasia without dysplasia. Individuals who have used corticosteroids or non-steroidal antiinflammatory drugs (NSAIDs) chronically (except for low dose aspirin equal to < 100 mg/day) will not be eligible. Patients will be accrued during the first study year, and will be followed until the last patient enrolled completes one year of treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BARRETT'S ESOPHAGUS: PREDICTORS OF PROGRESSION Principal Investigator & Institution: Reid, Brian J.; Associate Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant) This application brings together an experienced team of investigators into a P01 to study Barrett's esophagus (BE), the only established precursor of esophageal adenocarcinoma (EA), a rapidly increasing, highly lethal malignancy. BE is also a unique in vivo model of human epithelial neoplasia, and the P01 theme of genomic instability: its etiology, manifestations and progression focuses on fundamental mechanisms of human neoplastic progression. Thus, our primary and secondary goals are to (1) reduce morbidity and mortality of EA by early detection, prevention, or both and (2) elucidate mechanisms of human neoplastic progression in vivo that may be shared by other neoplasms whose early stages are less amenable to investigation. Our study design is a prospective investigation of the Seattle Barrett's Esophagus Cohort, one of the largest and best characterized in the world. All data in the P01 will be derived from this cohort, maintained by Core B (Clinical Research). Project 1 (Clonal Evolution) hypothesizes that the evolution of clonal lesions in p16, p53 and ploidy are intrinsic to mechanisms of neoplastic progression. It seeks to determine the extent to which they predict neoplastic progression in BE and to identify transcription patterns that mediate transitions from one stage of progression to another and give rise to EA. Project 2 (Epidemiology) hypothesizes that environmental exposures and host factors, including NSAIDs, serum selenium, bile reflux, high fat, low fruit and vegetable

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diet and being overweight, modulate progression. It seeks to determine the extent to which these factors are associated with the genetic markers that are developed in Projects 1 and 3, as well as clinical outcome as assessed by Core B. Project 3 (Genetic Instability) hypothesizes that loss of normal mechanisms that insure genomic stability is an early event that contributes to neoplastic progression in BE. The mechanisms that contribute to chromosomal and mitotic instability will be studied, and the utility of measures of genetic instability as predictors of clinical prognosis and as targets for therapeutic intervention will be determined. The P01 is highly collaborative and all projects and cores interact with each other. Thus, the clonal markers and measures of instability provided by Projects 1 and 3, respectively, become shared resources to advance the common goals of the P01. These interactions are facilitated by Core C (Bioinformatics/Biostatistics), which provides a framework for analysis of the complicated datasets of the projects and a vehicle for interproject and core communications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BARRETTS ESOPHAGUS--FAMILIAL DISORDER Principal Investigator & Institution: Cameron, Alan; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: Aim of study: Barrett's esophagus is a disorder associated with reflux and an increased risk of esophageal cancer. We previously showed an increased prevalence of symptoms of gastroesophageal reflux in first degree relatives of patients with Barrett's esophagus. The aim of the present study is to find whether first degree relatives of patients with Barrett's esophagus have an increased prevalence of this disorder compared to controls with reflux symptoms and no family history of Barrett's esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOMARKERS ADENOCARCINOMA

FOR

BARRETTS'S

ESOPHAGUS

AND

Principal Investigator & Institution: Peters, Jeffrey H.; Surgery; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 09-AUG-2001; Project End 31-JUL-2004 Summary: (Provided by applicant) The overall aim of this proposal is to develop a clinically valuable model of alterations in gene expression in patients, with Barrett's esophagus (BE) and Barrett's adenocarcinomas (EA). Currently, there is no accurate means of identifying, by either conventional histopathology or genetic testing the stage of disease or likelihood of Progression to dysplasia and adenocarcinoma. These facts have resulted in the need for widespread, expensive, yet relatively inaccurate surveillance of all patients with BE. We hypothesize 1) that the development and progression of Barrett's esophagus through the stages of intestinal metaplasia (IM), low grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma is associated with distinct and quantifiable differences in the expression patterns of carcinogenesisrelated genes; b) that genetic profiles based on quantification of expressions of a panel of progression-involved genes can be used to identify patients who have developed, or may be at higher risk of developing, adenocarcinoma or Barrett's metaplasia with dysplasia; and that c) that these adverse changes in gene expression related to development of BE can be reversed by clinical interventions. In specific aim 1, we will

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test these hypotheses by quantifying, at each stage in the Barrett's IM-LGD-HGDadenocarcinoma sequence, expressions (mRNA levels) of genes thought to be involved in malignant progression. These include cyclooxygenase-2 (cox-2) and related genes such as angiogenic factors, retinoic acid receptors, inducible nitric oxide synthase, telomerase, and others. In specific aim 2, we will test the ability of anti-reflux (Nissen fundoplication) surgery to reverse Cox-2 and cox-2-asociated gene expression changes associated with development of BE. Gene expression profiles will be determined in preand post-surgery tissue samples from the same patients. Demonstration of the ability of a clinical intervention such as surgery to normalize genetic patterns may profoundly alter the treatment of patients with BE, and potentially reduce the incidence of this highly lethal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOMARKERS IN BARRETT'S TUMORIGENESIS Principal Investigator & Institution: El-Rifai, Wa-El M.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The incidence of Barrett's esophageal and gastroesophageal junctional adenocarcinoma is rising faster than that of any other cancer in the United States. Barrett's Esophagus (BE) is a high risk factor for developing these malignancies. Our diagnostic, preventive, and therapeutic approaches to BE and esophageal adenocarcinoma are currently limited. In order to combat this health burden, novel avenues to better understand this lethal cancer's development must be employed. The development of diagnostic and prognostic biomarkers for patients with BE or its sequalae is desperately needed. Our specific aims are: Aim 1: Molecular profiling of Barrett's esophagus and adenocarcinoma, Aim 2: Characterization and validation of molecular targets and Aim 3: Development of diagnostic and prognostic biomarkers for BE progression risk. Global gene expression analyses using serial analysis of gene expression (SAGE) and protein profiling using high resolution 2D gels and mass spectrometry as proposed in this application will characterize the molecular signatures for the development of Barrett's esophagus and incorporate them into a working model of Barrett's tumorigenesis. Our combined mRNA and proteomic analysis approaches will facilitate the discovery of molecular biomarkers such as genes encoding secreted and cell surface proteins. Confirmation of biological and clinical importance in expanded functional and validation testing will be continued. Signature biomarkers once validated as critical in Barrett's adenocarcinoma development have important practical as well as biological implications for improved early diagnostic, prognostic, and therapeutic advances in this lethal disease. Moreover, our analyses will facilitate the discovery of molecular biomarkers such as genes encoding secreted and cell surface proteins providing new opportunities for biomarker assays in the serum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOMATHEMATICAL APPROACHES TO CANCER Principal Investigator & Institution: Moolgavkar, Suresh H.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-MAR-1988; Project End 30-JUN-2006 Summary: (provided by applicant): Clones of intermediate cells on the pathway to cancer, such as adenomatous polyps and altered hepatic foci, are often observed in humans and animals. These lesions provide insights into the earliest stages of the

12


carcinogenic process. Because clonal expansion of cells that are partially transformed can increase the probability of cancer substantially, a quantitative understanding of these lesions is key to understanding cancer rates. The broad objective of this project is to continue the development of mathematical, statistical and computational tools, within the paradigm of multistage carcinogenesis, for the quantitative analyses of early lesions on the pathway to malignancy. The fundamental goals of these analyses are to study the temporal evolution of these lesions, to estimate the rate of initiation of the lesions, and the rates of cell division and apoptosis of the partially transformed cells that comprise the lesion. Information on such early lesions is typically available from initiationpromotion experiments, particularly in the rodent liver.In previous work mathematical expressions have been developed for the number and size distribution of intermediate lesions on the pathway to malignancy and used for analyses of initiation-promotion experiments in rat liver. This proposal plans to extend this work in light of new biological information. In addition to continuing work on analyses of liver foci in rodents, the research proposed here will investigate intermediate lesions in the human colon and in patients with Barrett's esophagus, a high-risk precursor condition for adenocarcinoma of the esophagus. In addition to the mathematical and statistical problems associated with clonal growth models within the paradigm of multistage carcinogenesis, both analyses of liver foci and analyses of lesions in Barrett's esophagus present diverse problems. Recognizing that modeling is an iterative process an integral part of this effort will be collaboration with experimentalists and human biologists, in particular Dr. Michael Schwarz, University of Tubingen, an expert on the rodent liver system, Dr. John Potter, an epidemiologist with expertise on colon cancer and Dr. Brian Reid, Director of the Seattle Barrett's Esophagus Project. The results of analyses will be used to help generate biologically relevant questions and hypotheses and to plan further experiments and studies, which, in turn, will lead to more refined models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHROMOSOMAL INSTABILITY Principal Investigator & Institution: Rabinovitch, Peter S.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Project 3 will assess chromosomal and mitotic instability in Barrett's Esophagus (BE) and collaborate closely with Project 1 in assessing relationships between markers of genetic instability and p16 and p53 abnormalities, and with Project 2 in evaluating the interactions of genetic instability markers with environmental risk and protective factors. These understandings will give insight into the mechanisms of neoplastic progression in this model system, will further refine the prediction of cancer risk in BE patients and will help elucidate both the mechanisms of environmental damage and new strategies for intervention to prevent disease progression. We hypothesize that the loss of normal mechanisms that insure genomic stability may be an early event in neoplastic progression in BE, one that facilitates progression to cancer through the progressive loss of tumor suppressors by genetic deletion and rearrangement. We also hypothesize that there are multiple mechanisms of genetic instability at play during neoplastic progression and that they may be important at different stages of progression. In this project, we will: (1) quantitate chromosomal instability; (2) determine when genetic instability arises within the sequence of genetic events that leads to cancer in Barrett's esophagus; (3) examine mechanisms that contribute to genetic instability; and (4) determine the potential role of measures of

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genetic instability as predictors of clinical prognosis and as targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHROMOSOME ALTERATIONS IN BARRETT'S ESOPHAGUS Principal Investigator & Institution: Paulson, Thomas G.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Description) The incidence of esophageal adenocarcinoma (EA), a rapidly fatal cancer with 5-year survival of less than 10 percent, has risen more then 350 percent over the past 20 years. Neoplastic progression in Barrett's esophagus (BE), the precursor to EA, is characterized by progressive genetic instability, including mutations (p53, p16), promoter hypermethylation (p16), aneuploidy and chromosomal instability (LOH, deletions and amplifications). Barrett's esophagus is an excellent model of human neoplastic progression because endoscopic surveillance is recommended, permitting serial samples to be evaluated over time in the same patient. Shortened telomeres, p53 and p16 inactivation occur before EA. We hypothesize that telomere shortening causes chromosomal instability in BE as has been proposed in model systems. However, relationships among p16/p53 inactivation, reactivation of telomerase, and chromosomal instability during human neoplastic progression are largely unknown. In this proposal, I will investigate the hypothesis that telomere shortening, abrogation of p16 and p53 function and telomerase reactivation interact to mediate chromosomal instability in BE. We propose to measure telomerase activity in BE samples in 325 patients from the Seattle Barrett's Esophagus Cohort, an extremely well characterized cohort for whom p53 and p16 status and flow cytometric data are already known. We will use clonal ordering to determine relationships among p53 inactivation, p16 inactivation, telomerase reactivation and the development of chromosomal instability, using alterations on chromosome 18 as a model of instability. Chromosome 18 is an appropriate model because it is frequently (75 percent of cases) altered in EA (LOH events, amplifications and deletions) and these alterations are selected before the development of cancer. The methods used in these analyses will include TRAP assays to measure telomerase activity and microsatellite LOH and microarray comparative genomic hybridization (CGH) to assess chromosomal instability. The results from these analyses will be of interest to both clinical and basic researchers in studying EA and other cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CORE--CLINICAL RESEARCH Principal Investigator & Institution: Blount, Patricia L.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The overall goal of Clinical Research Core B is to support the individual projects and the overall specific Aims proposed in this Program Project. This goal will be accomplished by providing long-term follow-up of an established cohort of patients who have Barrett?s esophagus in which longitudinal investigations of the development of esophageal cancer are conducted. The Seattle Barrett's Esophagus Program (the patient base for Core B) has an established cohort of 325 active participants who have Barrett's esophagus and who are in various stages of progression to cancer. These patients are in periodic endoscopic biopsy surveillance for

14


detection of esophageal adenocarcinoma when it is early and curable with surgery. The lifetime risk of developing cancer in Barrett's esophagus is low, estimated to be in the range of 5-10 percent. However, the Seattle Barrett's Esophagus Program specializes in the surveillance of high-risk patients. More than 25 percent of the Program cohort has an estimated 5-year cancer risk of 28-59 percent and the Program gets regular referrals of these patients because it is difficult for them to be safely or practically managed in the community. Core B, therefore, consists of a substantial number of both high-risk and low-risk patients, providing a unique resource for the conduction of investigations of progression to cancer. Core B is essential to the Program Project. All data generated by the individual Projects can be linked directly to a specific endoscopy, biologic specimen or patient interview coordinated by Core B. The specific Aims of Core B are: (1) To obtain longitudinal tissue samples from Barrett's epithelium for histologic diagnoses and coordinate the acquisition of the corresponding research biopsies, gastric fluid aspirates and blood samples from the Same patients for molecular biologic and epidemiologic investigations as proposed in Projects 1, 2, and 3; (2) To provide longterm follow-up of a large cohort of patients for molecular genetic investigations (Projects 1 and 3), the outcomes of which may result in novel endpoints for epidemiologic investigations (Project 2) and provide scientific rationale for chemopreventive therapies; (3) To continue to recruit new patients to the Program by referral from community gastroenterologists, thus, maintaining a large well-characterized cohort of patients for the investigations proposed in Projects 1, 2 and 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MOLECULAR EPIDEMIOLOGY AND ECOGENETICS Principal Investigator & Institution: Spitz, Margaret R.; Professor and Chair; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002 Summary: The overall goal of this research core is to develop and validate genetic markers for cancer susceptibility. By incorporating molecular genetics and cytogenetics into population studies, the investigators hope to gain insights into the complex interactions between genetic and environmental determinants of cancer. Of particular interest are the low penetrance genes that may modulate one's response to environmental exposures and contribute to the etiology of sporadic cancers. Specific aims include maintaining and expanding communication and scientific interaction among Core and other Center members, as well as non-Center members; strengthen current and promote future research activities in the area of genetic susceptibility to environmental disease; stimulate and facilitate intra- and inter-Core grant renewals and new investigators-initiated grant proposals; and serve in consultative and collaborative roles across research and facility cores to include concept development, study design, human tissue procurement and environmental data collection. Major areas of research focus in this Core encompass: 1) the assessment of phenotypic markers of DNA damage and repair as markers of susceptibility to carcinogenesis, 2) the evaluation of polymorphisms in select metabolic and DNA repair genes and DNA adducts in the etiology of lung, bladder, breast, and pancreatic cancers, and 3) the development of statistical models for cancer risk assessment by combining biomarkers and for genotypephenotype and surrogate-tissue marker correlation. Intra-Core 4 and inter-Core collaborative studies being conducted or completed include the following: 1) a casecontrol study of lung cancer examining cytogenetic and molecular determinants of tobacco carcinogenesis, 2) a study of genetic and environmental determinants, including phytoestrogen intake, of prostate cancer progression, 3) a genetic epidemiologic study of

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gliomas in relation to family history and genetic susceptibility markers, 4) a study of microsatellite instability and the risk of bilateral breast cancer, 5) a study of genetic polymorphisms, epidemiologic risk factors and differences in breast cancer survival among different ethnic groups, 6) a study of DNA adducts, P53 mutation spectrum, oxidative DNA damage and breast cancer risk among premenopausal women, 7) a study of molecular genetics of hereditary nonpolyposis colorectal cancer, 8) a study of modifier genes that influence age-associated risk of colorectal cancer, 9) two studies evaluating environmental and genetic determinants of advanced prostate cancer, 10) studies of second malignancies after treatment for hairy cell leukemia, acute myelocytic leukemia, 11) a study of cutaneous malignant melanoma and non-melanoma skin cancer, 12) a study of linkage and linkage disequilibrium, methods for traits, 13) a study of genetic susceptibility of bladder cancer, 14) a study of mutagen sensitivity and progression in Barrett's esophagus, 15) a study of the genetic, hormonal and behavioral determinants of obesity, 16) a pilot study of breast and colorectal cancers among Egyptians and organochlorine pesticides exposures, and 17) a pilot study to examine associations of mutagen sensitivity, oxidative damage and DNA adducts in lung cancer. The stated long term goal of this Core is to develop a validated risk model for cancer, such as lung cancer, to take into account simultaneously the effects of numerous genetic and environmental factors and the nature of subgroups (women, never-smokers, young subjects, ethnic minorities, etc). Future plans include the use of funds from the Tobacco Settlement for the State of Texas to establish an archival laboratory for the long-term storage and tracking of biological specimens and a centralized genotyping core. It also plans to expand in the area of nutritional epidemiology, and in its molecular epidemiologic studies to include brain and lymphoid malignancies. Future plans also include the development of a genotyping chip, in collaboration with Genometrix, expansion of the CRED website and implementation of multivariate statistical analysis to the large database that will be generated by incorporating chip technologies into studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIAGNOSIS OF DYSPLASIA BY FLUORESCENCE SPECTROSCOPY Principal Investigator & Institution: Van Dam, Jacques; Associate Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 25-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Description) The goal of this research proposal is to provide salary support to facilitate the advancement and completion of an NCl-funded clinical research proposal. The Principal Investigator, a clinically active physician scientist, is a collaborator on NCI R01 CA 53717 "Real Time In Vivo Diagnosis of Dysplasia by Fluorescence." The goal of the R01 is, in part, to develop endoscope-compatible, fluorescence spectroscopy systems for the real time detection of precancerous (dysplastic) alterations in the luminal gastrointestinal tract. Both fiber optic-based contact probe techniques for localized detection and fluorescence spectral endoscope systems for wide area imaging of disease will be developed and applied clinically. Multi-wavelength excitation fluorescence and reflectance system will be used to characterize the optical/spectroscopic properties of relevant tissue types. The results of this study will be used to select optimal excitation wavelength(s) and design fiber probes with controllable sampling depth for targeting detection of superficial lesions. By combining this information with tissue optical parameters, models of colon and esophageal fluorescence measured at colonoscopy and gastroscopy respectively, will be developed. Inverse modeling will be developed for extracting histopathological

16


information from the clinical spectra. The existing fluorescence imaging colonoscope will be modified for additional clinical studies, including application in patients with Barrett's esophagus. The techniques developed in this program will be clinically tested for rapid detection of colorectal dysplasia/carcinoma in chronic ulcerative colitis and dysplasia in Barrett's esophagus and as such are "translational" in nature. Based on extremely successful preliminary data, light (white light) scattering spectroscopy (LSS) will be used to determine the size and degree of "crowding" of nuclei of superficial mucosal cells in the columnar-lined (Barrett's) esophagus. LSS will be used to guide the endoscopic detection (and pathological grading) of mucosal dysplasia. The Principal Investigator is devoted to training clinical researchers and will continue the formalized instruction and mentoring of young clinicians so that they may successfully engage in meaningful clinical research. In this way, the Principal Investigator will help mentor the next generation of physician scientists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOSCOPIC LIGHT SOURCE FOR PDT Principal Investigator & Institution: Hsi, Richard A.; Amt, Inc. 508 Heartwood Rd Cherry Hill, Nj 08003 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract): We propose to continue to develop and test a self-contained light delivery device for use in photodynamic therapy (PDT) for Barrett's esophagus. This device employs distally located semiconductor lasers at the end of a thin coaxial cable inserted into a balloon catheter. In Phase I, we successfully developed prototype units that produced sufficient light for PDT treatment and evaluated different scattering media to increase the uniformity of the light emission. In Phase II, we intend to design enhancements that produce uniform light distribution and increase the illuminator's flexibility. A light and fluorescence detection system will be incorporated into the balloon's wall. Unit will be tested for safety and efficacy in an animal model. A significant advantage to this source design is that individual segments or spot locations across the illuminator can be turned on or off and the intensity changed during treatment. The light and fluorescence detection systems will allow more uniform treatment and help optimize treatment parameters (fluence, fluence rate, photosensitizer dose, and photosensitizer/light interval) to maximize the PDT effect and minimize toxicity. The diode illuminator will be capable of changing light dosing parameters to fit optimal conditions for any situation including the use of different photosensitizing compounds. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENHANCED PHOTODYNAMIC TREATMENT OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Nishioka, Norman S.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002 Summary: APPLICANT'S (Provided by Applicant) The ultimate goal of this project is to improve the treatment of dysplastic Barrett's esophagus (BE) by optimizing photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). The incidence of esophageal adenocarcinoma is rising faster than any other cancer and BE is the primary risk factor for developing this malignancy. PDT has become a commonly used method for eradication of BE with minimal morbidity. ALA is an attractive photosensitizer (PS)

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for PDT because it can be given orally just prior to illumination and has minimal side effects. However, ALA has not gained widespread acceptance because of its poor ablation efficiency relative to other photodynamic agents. This proposal describes studies modulating various ALA-PDT treatment parameters with the goal of improving PDT efficiency. There are three specific aims: (1) enhance ALA-PDT using differentiation therapy, (2) enhance ALA-PDT by modifying light delivery and (3) develop short-term surrogate endpoints that predict the long-term clinical outcome of ALA-PDT. These aims will be accomplished by performing a single prospective, randomized clinical trial in patients with BE and high-grade dysplasia (HGD) or T1N0M0 esophageal cancer. Cell differentiation is known to increase the production of protoporphyrin IX (PPIX) which is the PS induced by ALA and retinoids are differentiating agents capable of redirecting cells to their normal phenotypic maturation. The ability of 13-cis retinoid acid to induce differentiation and improve ALA-PDT will be determined during this trial. In addition to examining the effect of 13-cis retinoid acid on clinical outcome, the effect of 13-cis retinoid acid on the enzymes involved in the generation of PPIX will be analyzed. In a separate arm of the trial the hypotheses that lower light fluence rates and fractionation of light dose enhance the clinical efficacy of ALA-PDT will be tested. In the third specific aim, an in vivo dosimeter will be developed that will enable spectroscopic measurements to be taken during PDT. These measurements will be used to identify parameters that predict the clinical outcome of PDT. These studies will significantly advance our understanding of ALA-PDT, enhance its clinical use for the treatment of dysplastic BE and are likely to be applicable to PDT of other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESOPHAGUS

EPIDEMIOLOGIC

CASE-CONTROL

STUDY

OF

BARRETT'S

Principal Investigator & Institution: Shaheen, Nicholas J.; Assistant Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: The long-term objectives of this project are to advance the understanding of the pathophysiology and management of Barrett's esophagus, and to achieve further formal training in epidemiology and outcomes research for the applicant. Dr. Shaheen, the applicant, is an Assistant Professor at UNC and is Co-Director of the Center for Esophageal Diseases. His mentor, Dr. Robert Sandler, is an established GI epidemiologist, and Director of the Center for Gastrointestinal Biology and Disease (CGIBD). They propose a combined didactic and clinical research experience, utilizing the resources of the UNC School of Public Health, the GI Division and the CGIBD to foster Dr. Shaheen's demonstrated interest in outcomes research. Dr. Dawn Provenzale from Duke University will also provide instruction and mentoring, as well as expertise in the subject area, Barrett's esophagus. The study proposed as part of the clinical training is a case-control study of Barrett's esophagus. Barrett's esophagus is a premalignant lesion of esophageal adenocarcinoma, a usually lethal cancer whose incidence is increasing in epidemic proportions. Barrett's is associated with gastroesophageal reflux. Because we cannot adequately stratify risk for Barrett's among those with reflux, authorities recommend that all those with chronic reflux undergo endoscopic screening for Barrett's. Better stratification of Barrett's risk would allow for more targeted usage of screening endoscopy. The specific aims of this study are: 1) To evaluate the relationship between obesity and Barrett's, 2) To assess the role of H. pylori infection and Barrett's, 3) To assess the predictors for dysplasia among those with Barrett's, and, 4) To assess the

18


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 Principal Investigator & Institution: Vaughan, Thomas L.; Professor and Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Dramatic increases in the incidence of esophageal adenocarcinoma (EA), a rapidly lethal cancer, have occurred in the U.S. and Western Europe over the last two decades. The vast majority of cases occur among Caucasian men. The underlying reasons for the rapid increase in incidence and the unusual gender and race patterns remain largely unknown, although the increasing prevalence of obesity in the U.S. likely plays a role. Most EAs arise in a metaplastic epithelium termed Barrett's esophagus (BE) that develops in approximately 10 percent of persons who have chronic gastroesophageal reflux. Persons with BE are at high risk, with approximately 0.5 - 1.0 percent per year progressing to cancer. Environmental exposures and host factors may be important determinants of the likelihood of developing genetic instability in BE, and of progressing through a succession of abnormalities to cancer. In this well-established cohort (N=461; mean follow-up = 5 years), suspected risk and protective factors for EA will be examined to quantify the extent to which they predict risk of neoplastic progression in persons with BE, and to identify particular genetic and histologic abnormalities with which they are most closely associated. In addition to EA as an outcome, intermediate endpoints will be used that have been validated, or are expected to be as part of Projects 1 and 3, as predictors of EA. These include aneuploidy, elevated 4N fraction, high grade dysplasia, and alterations (LOH, mutation, methylation) involving p53 and p16. Specific aims are to evaluate as potential protective factors: a) use of non-steroidal anti-inflammatory drugs (NSAIDs), and b) increased serum selenium concentration; and to evaluate as factors that may increase risk: c) overweight and an abdominal fat distribution, d) bile reflux, and e) a diet high in fat and low in fruits and vegetables. Proportional hazards regression will be the main analytic approach. Successful attainment of the above specific aims will likely lay the scientific foundation for future prevention trials by identifying important risk factors for esophageal adenocarcinoma, identifying specific interventions that could be tailored to individual patients, and illuminating mechanisms of action which could be tested experimentally. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY AND INCIDENCE OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Corley, Douglas A.; 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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EPITHELIAL-REFLUXATE

INTERACTIONS

IN

BARRETT'S

Principal Investigator & Institution: Triadafilopoulos, George; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The major objective of our studies is to understand the molecular changes that occur in response to acid and bile exposure in normal and Barrett's esophagus (BE). BE is a metaplastic premalignant condition of the esophagus that is associated with an increased risk of up to 30-fold of developing esophageal adenocarcinoma. Exposure of the esophagus to the duodeno-gastro-esophageal (DGE) refluxate, important constituents of which include acid and bile, is a major risk factor for the development of BE and subsequent esophageal adenocarcinoma. Our overall hypothesis is that identifying acid and bile stimulated up- or down regulated genes in the normal esophagus and Barrett's epithelium, and characterizing the signaling pathways that are involved, should provide potential diagnostic and therapeutic targets

20


and essential clues regarding the mechanisms of esophageal metaplasia and abnormal cell proliferation in BE. Our specific aims and hypotheses are: (i) Use a human microarray approach, ex vivo, to identify the genes that are modified in response to acid or bile in normal esophagus, BE and duodenum. This aim is based on the hypothesis that the DGE refluxate modulates the genetic program of normal esophageal, BE and duodenal epithelia differently, in a refluxate constituent-dependent fashion. (ii) Identify the acid or bile-induced modified genes in squamous esophageal and Barrett's cell lines. This aim is based on the hypothesis that tissue cultured cell lines, due to their ability to provide an unlimited supply of RNA for gene profile analysis, may provide complimentary information to that obtained using ex vivo biopsies. (iii) Study the signaling cascades of protein kinase C, Cox-2, and Src kinase that are involved in acid/bile-induced stimulation, and define their potential interactions. This aim is based on the hypothesis that characterizing the signaling pathways that are involved in acid and bile stimulated cell proliferation complements the microarray gene profiling strategies and may provide potential complimentary targets for decreasing the risk of dysplasia and adenocarcinoma in BE. Overall, our study seeks to define the molecular signals that play a role in developing metaplasia and that regulate the acid- and bilemediated responses in the esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESS AND OP IN THE MANAGEMENT OF BARRETT"S ESOPHAGUS Principal Investigator & Institution: Lovat, Laurence; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): 1. Laboratory studies in rats. To use elastic scattering spectroscopy (ESS) to detect changes in tissue below the most superficial layer in the gastrointestinal tract. The ultimate purpose of this is to detect residual glands in the esophagus that may persist under regenerated squamous epithelium when PDT is used to treat Barrett's esophagus. 2. Laboratory studies in rats. To use elastic scattering spectroscopy (ESS) to assess the effect of PDT on the mucosa of the rat stomach. The purpose is to find out if ESS can determine whether glandular mucosal ablation is partial or complete and when is the best, and earliest, time after PDT to look. 3. Clinical. To refine ESS analysis for detection of dysplasia in Barrett's esophagus. This will involve a more sophisticated analysis of data we already have, gathering new data to improve the algorithms for spectral analysis and assessing these algorithms prospectively. The possibility of using ESS to detect aneuploidy will also be explored. 4. Clinical. To use OP and ESS to manage treatment and to monitor the results of PDT for dysplasia in Barrett's esophagus. This will include OP measurements of photosensitizer levels at the time of PDT to optimize light dosimetry and ESS measurements of tissue response at times from immediately after light delivery until healing is complete. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EVOLUTIONARY DYNAMICS OF BARRETT'S ESOPHAGUS NEOPLASIA Principal Investigator & Institution: Maley, Carlo C.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Description): The cell lineages in neoplastic tissues are evolving under the twin dynamics of mutation and clonal expansion. This is the basis for both its

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virulence and our difficulties in treating it. We hypothesize that a subset of the mutations observed in the progression to cancer confer beneficial selective effects on the cell. Furthermore, we hypothesize that the interactions between these clonal populations in and around the neoplastic tissue determine the progression to cancer. The aim of this project is to identify these selective mutations and to infer the interactions between the mutant clones in Barrett's Esophagus that eventually lead to the development of esophageal adenocarcinoma. This analysis will be based on loss of heterozygosity data, promoter methylation, single nucleotide polymorphisms, and gene expression data for homogeneous subpopulations of cells sampled from neoplastic tissue in patients with Barrett's Esophagus. The tissue samples come from biopsies of selected patients in the Seattle Barrett's Esophagus Project (N=285). Data mining will be used to identify mutations that are associated with clonal expansion as well as inhibition of neighboring clones. The order of genetic events in the progression to esophageal adenocarcinoma will be determined by phylogenetic reconstruction of the cell lineages in the neoplastic tissue of each patient. Machine learning techniques, such as the EM algorithm, will be employed to infer missing data and the effects of unsampled mutations. Computational modeling will be used to generate comparison data for null hypotheses as well as to generate experimental predictions from our understanding of the progression to cancer. This is the first step in my long-term career goal to contribute to medicine through the use of computational and theoretical methods. Working at the Fred Hutchinson Cancer Research Center will facilitate the transition from my background in computer science and evolutionary theory, to an independent research program based on the analysis of cellular and molecular dynamics of cancer. The challenge of this project is the integration of diverse molecular and epidemiological data into a coherent and detailed understanding of the progression to cancer in the neoplasm of a model system. 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 11100 Euclid Ave Cleveland, Oh 44106 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

22


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 •

Project Title: FAST OCT TECHNOLOGY FOR COMPREHENSIVE DIAGNOSTIC IMAGING Principal Investigator & Institution: De Boer, Johannes F.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Over the past 10 years, optical coherence tomography (OCT) has undergone a rapid development from inception to a versatile method for non-invasive high-resolution optical imaging. A wide range of medical diagnostic applications has been explored in ophthalmology, cardiology and in early cancer diagnosis in general. Preliminary studies have demonstrated that OCT can facilitate the accurate diagnosis of a variety of diseases when used in a point-sampling protocol analogous to random biopsy. The potential diagnostic applications having the highest impact, however, require screening or surveillance of large tissue volumes. The relatively slow image acquisition rate of current OCT technology therefore represents a significant barrier to its utility as a powerful clinical tool. Since the current technology commonly operates at its theoretical limit for efficient light collection, dramatic improvements in imaging speed can only be obtained through a technological paradigm shift. We propose to develop a new, parallel detection principle for OCT that is several hundred-fold more efficient than current state of the art technology and that provides vastly improved image acquisition rate and resolution. The system design of the proposed technology is tailored to three high-impact clinical goals: early detection and monitoring of glaucoma, the second-leading cause of blindness in the U.S, detection and characterization of vulnerable coronary plaques responsible for acute myocardial infarction, and comprehensive surveillance for esophageal neoplasia in patients with Barrett's esophagus. Three clinical pilot studies, using technology developed in this work, will be conducted to test system performance relevant to achieving these goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GASTROINTESTINAL CANCER SCREENING AND SURVEILLANCE Principal Investigator & Institution: Provenzale, Dawn T.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-MAR-2005 Summary: (Applicant's Description) My research plan focuses on gastrointestinal cancer screening and surveillance. The integrated research approach targets three clinical areas (screening for colorectal cancer, and surveillance of patients with Barrett's esophagus and ulcerative colitis). The study methods link decision modeling with clinical research to answer important clinical questions regarding screening and surveillance. The integrated research process includes: 1) Identifying the relevant screening and surveillance questions for study, 2) structuring a decision analytic model (using published literature) to answer the study questions, 3) identifying the optimal strategy

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given the available data, 4) targeting critical parameters in the model for which there are incomplete data, 5) designing and implementing observational studies for primary collection of these data, and 6) integrating the results of the clinical studies into decision models to provide clinicians and policy makers with new, patient specific data about the optimal management strategy. Research projects focus on the development of the acceptable and cost-effective colon cancer screening strategies for veterans. Future projects will determine the costs and resource needs to implement these preferred strategies. Another study evaluates risk factors for presentation with late stage colorectal cancer. If modifiable factors such as access to screening, or physician delay in follow-up of positive screening tests are identified, then interventions can be made to improve access and reduce delay with the aim of reducing colorectal cancer mortality. Ongoing and future studies will examine the health related quality of life of patients with Barrett's esophagus and ulcerative colitis using standardized measures (SIP, SF-36, RFIPC, TTO). The results will be summarized and incorporated into the decision models to determine their effect on surveillance strategies. The other critical component of my career plan is the structured mentoring program for gastroenterology/health services research fellows. The program integrates coursework leading to a Master of Science in Clinical Research with a mentoring program that provides the fellow with the opportunity for patient centered research experience. There is a gradual increase in his/her research independence under my supervision, leading to the design and execution of his/her own research project, including data analysis, abstract and manuscript preparation and presentation of the study results at a national meeting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC EPIDEMIOLOGY OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Romero, Yvonne; Mayo Clinic 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 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

24


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: MALIGNANCY

GENOMICS:

ESOPHAGEAL

METAPLASIA-ASSOCIATED

Principal Investigator & Institution: Meltzer, Stephen J.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Barrett's esophagus is a highly premalignant disease of unknown prevalence, but it predisposes to the development of esophageal adenocarcinoma, which is increasing at alarming rates in Western countries. The molecular genetics of esophageal adenocarcinoma and its precursor lesion, Barrett's esophagus, has been studied intensively in recent years. However, a better knowledge of the molecular alterations occurring in this setting will yield several benefits. Firstly, the discovery of novel molecular alterations will yield clues to biological pathways underlying Barrett's-associated neoplastic transformation, and these clues may lead to better in vitro and in vivo models of this disease. Secondly, molecular alterations themselves can be used as markers of early detection, disease progression, or ultimate prognosis in patients with Barrett's or cancer. Thirdly, these molecular alterations can be pursued as possible therapeutic targets for intervention, in both the prevention and treatment of this disease. The Aims of the current proposal will be to discover novel molecular alterations in Barrett's metaplasia and neoplasia, and to concentrate on the second of these benefits, i.e., to perform translational research to determine the potential value of these alterations as markers of disease progression. By using the same cDNA microarray platform to determine changes in DNA copy number, methylation status, and gene expression level, we will facilitate the translation of molecular genetic data from the genomic, to the epigenetic, to the transcriptomic, and finally to the protein (biomarker) level. This final level will employ tissue microarrays to test and validate specific candidate genes derived from the first three levels of study. These goals will be implemented by pursuing the following Aims: Aim 1. To perform global exploration for changes in DNA copy number in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence (Barrett's neoplasia), using cDNA microarray-based comparative genomic hybridization (microarray-CGH). a) Global patterns of DNA amplification and deletion will be identified by microarray-CGH and characterized at each stage of Barrett's neoplasia, using hierarchical clustering, significance analysis of microarrays (SAM), and artificial neural networks, b) Specific cDNAs showing the most consistent and/or marked alterations in DNA copy number will be identified, characterized and validated using quantitative real-time PCR, for further study in Aim 4. Aim 2. To perform global epigenetic profiling at various stages in Barrett's neoplasia, using methylation-specific oligonucleotide microarrays. The genome will be screened for novel targets of DNA hypermethylation in various stages of Barrett's neoplasia, using methylation-specific oligonucleotide microarrays. Aim 3. To Using ANNs, to perform analyses of global gene expression data in Barrett's neoplasia. Results of genomic studies in Aims 1 and 2 will be correlated with global expression data in order to identify the genes most significantly different at both the genomic and transcriptomic levels at each stage of Barrett's neoplasia, for further study in Aim 4. Aim 4. Using tissue microarrays, to evaluate and

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validate potential biomarkers at the protein level in Barrett's neoplasia. Potential biomarkers identified in Aims 1-3 will be studied individually for expression at the protein level in all stages of Barrett's neoplasia, using tissue microarrays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING SCREENING & SURVEILLANCE IN BARRETT'S PATIENTS Principal Investigator & Institution: Tearney, Guillermo J.; Assistant Professor of Pathology; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Barrett's esophagus, also termed specialized intestinal metaplasia (SIM) of the esophagus, is the precursor to esophageal adenocarcinoma, a lethal cancer that is rising in incidence at an alarming rate. The longterm objective of this proposal is to decrease the mortality associated with esophageal adenocarcinoma. Evidence supports screening a large percentage of the adult population to identify patients with SIM. Regular surveillance of patients with Barrett's can then identify dysplasia and adenocarcinoma at an earlier, more treatable stage. The only accepted method for screening for SIM is biopsy through endoscopic guidance. Although this approach is well established, the vast majority (96-98%) of adenocarcinomas are found in patients without prior diagnosis of SIM. Important factors that contribute to the inadequacy of endoscopic biopsy for screening are cost and accuracy. The first goal of this work is to develop and test an accurate, less expensive screening method for Barrett's esophagus. We have previously demonstrated that optical coherence tomography (OCT) can accurately distinguish esophageal SIM from normal squamous epithelium in patients undergoing endoscopy. In the proposed research we will develop methods for comprehensively screening the entire distal esophagus with OCT without requiring endoscopy or patient sedation. Current surveillance protocols consist of upper endoscopy with multiple random biopsies. Since dysplasia and adenocarcinoma are focal diseases, random biopsy is subject to sampling errors and high rates of false negative diagnoses. The second goal of this research is to develop and test a more sensitive method for surveillance in patients with Barrett's esophagus based on optically guided biopsy. Preliminary studies suggest that OCT can further differentiate SIM to identify dysplasia and adenocarcinoma. We propose to systematically image the entire Barrett's region and direct biopsy to locations that contain the most severe disease. The proposed work will expand the current diagnostic capabilities of OCT, develop a standalone imaging method for systematically evaluating the distal esophagus, and test these new methods for screening and surveillance in patients. This program will provide physicians with an improved diagnostic tool that will impact clinical practice as well as be used for future studies to address unresolved controversies regarding the natural history and treatment of patients with this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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INOS,

COX-2,

AND

ARGINASE

IN

MURINE

BARRETT'S

Principal Investigator & Institution: Wilson, Keith T.; Associate Professor of Medicine; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Barrett's esophagus (BE) represents a substantial health care burden because it has a high frequency of progression to dysplasia and

26


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: MECHANISMS OF ACID RESISTANCE IN BARRETT'S ESOPHAGUS Principal Investigator & Institution: Orlando, Roy C.; Professor of Medicine & Chief; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Barrett's esophagus denotes the presence of specialized columnar epithelium (SCE) in distal esophagus. It develops in subjects with acid reflux disease as replacement for destroyed esophageal stratified squamous epithelium (ESSE). In 90%, it remains stable for life and irrespective of treatment since most - presumably because of its acid resistance - are (reflux) symptom-free. In one sense, then, Barrett's is a successful adaptation for esophageal protection. Barrett's, however, has a high cell turnover rate which establishes it as a premalignant lesion that increases esophageal cancer risk 40-fold over the general population. Though clinically important, little is known about the biology of SCE, and specifically about the mechanisms for acid resistance that are at the heart of its very existence. Therefore the goals of this proposal are: a) to define the preepithelial and epithelial mechanisms for SCE's survival under acidic stress: b) compare them to ESSE in Barrett's in order to test the hypothesis that SCE develops in GERD because of intrinsic mechanisms that make it more acid resistant than ESSE, and c) since alcohol and cigarette smoking increase the risk of malignancy in SCE, test the hypothesis that this risk reflects the ability of these

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agents to shorten cell survival I (which increases cell turnover) by impairing SCE's ability to protect itself under an acidic stress. The specific aims are to determine in SCE and ESSE in Barrett s: 1) the magnitude of the lumen-to-surface pH gradient and role of mucus and HCO3, 2) the permeability of the apical membrane-junctional complex to H+, 3) the total cell buffer capacity and role of carbonic anhydrase, 4) the nature, location and activity of transporters for pHi regulation, 5) the effect of alcohol and smoking on cell survival under an acid stress, and to: 6) compare the results to ESSE in those without esophageal disease. Studies are performed using esophageal biopsies for cell isolation, culture and mounting in mini-Ussing chambers. Techniques include: pH icroelectrodes, immunohistochemistry, impedance analysis and fluorescence microscopy. Achievement of the proposed goals will yield information of fundamental importance to understanding the pathogenesis and malignant potential of SCE in reflux subjects and provide insights into possible novel strategies for its prevention, stabilization or selective eradication for reduction of cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

28


major disease groupings (RE, BE, AC), as well as for the molecular subtypes of RE, BE and AC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •


MOLECULAR

MECHANISMS

UNDERLYING

BARRETT'S

Principal Investigator & Institution: Silberg, Debra G.; Assistant Professor; Medicine; 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): Barrett's esophagus is the transformation of the squamous epithelium of the esophagus to an intestinal type. The metaplastic tissue is preneoplastic and progresses to adenocarcinoma through a stepwise transition with a dysplastic intermediate stage. Esophageal adenocarcinoma is increasing in incidence yet little is known about the molecular mechanisms underlying the development of Barrett's esophagus, the earliest lesion. To understand the transformation to metaplasia it is necessary to investigate the genes that are involved at the initiation of the events. The research outlined in this proposal focuses on the identification and characterization of genes induced in Barrett's esophagus. It is our hypothesis that the elucidation of these genes is fundamental to the understanding of the molecular pathogenesis of Barrett's esophagus as well as its predilection to adenocarcinoma. The following interrelated specific aims will be pursued: Aim 1: To determine the genes that are induced in Barrett's esophagus through microarray analysis by comparing squamous epithelium to Barrett's esophagus. The genes selected for further evaluation will be those that may be important in cellular differentiation and proliferation. Preliminary studies have identified sixteen genes that meet these criteria. Further analysis of these genes and others identified will include: quantitative PCR for validation of the array results and localization of gene expression in tissue by either immunohistochemistry or in situ hybridization. Aim 2: To determine the functional significance of the genes identified in Specific Aim 1. Esophageal organotypic cultures will be propagated that are infected with retroviruses expressing the genes of interest. The cultures will be analyzed for changes in morphology and gene expression. It is anticipated that the results of these studies will lay the foundation for our understanding of the molecular mechanisms, which underlie the development of Barrett's esophagus. With this knowledge it will be possible to further study the genes in transgenic mice to better elucidate the significance of the genes in an in vivo system. The understanding of the fundamental properties of Barrett's esophagus, specifically the initiating molecular events, will allow for the development of better diagnostic, treatment and chemoprevention strategies to target the metaplasia to cancer process at an early stage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL CONFOCAL MICROSCOPE FOR MOLECULAR/CELLULAR IMAGING Principal Investigator & Institution: Wang, Thomas J.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): We would like to develop a new method of in vivo imaging using a miniaturized confocal microscope to study the biological processes of tumor development on the molecular and cellular level. This method has the potential to revolutionize cancer research. The long term objective of this project is to develop a

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technique to observe how tumors originate, progress, and invade. The behavior of cells will be monitored from images of sub-cellular constituents tagged with green or yellow fluorescence protein (GFP, YFP). A miniaturized confocal prototype has already been developed and its performance has been demonstrated with ex vivo images. We plan to improve this microscope with a new design using a dual-angle-axis architecture. This design offers improved resolution and working distance, which will facilitate in vivo imaging. We then plan to study two tumor models, medulloblastoma in a mouse model that has been associated with decreased expression of the ptc1 gene, and dysplasia in Barrett's esophagus and colonic adenomas. We will use these models to develop the new microscope. First, the performance of the tabletop dual-angle-axis prototype will be characterized by reflectance and fluorescence images of cultured cells and tissues sections expressing GFP/YFP and by biopsy specimens of Barrett's esophagus and colonic adenomas. Then, images will be collected from post-natal ptc1 knock-out mice expressing GFP/YFP to monitor angiogenesis, tumor invasion, and response to therapy. Next, the results of these studies will be used to develop the redesigned miniaturized microscope using Micro-Electro-Mechanical Systems (MEMS) fabrication technology. The miniaturized microscope will be used to study medulloblastoma in ptc1 knock-out mice in vivo and dysplasia in Barrett's esophagus and colonic adenomas during routine endoscopy. The specific aims of this research are as follows: 1) Measure the transverse and axial resolution, signal-to-noise, and field of view of the tabletop dual-angle-axis confocal prototype. 2) Collect reflectance and fluorescence images from cultured cancer cells expressing GFP/YFP. 3) Confirm the performance of the tabletop prototype with reflectance and fluorescence images collected from biopsy specimens of Barrett's epithelium and colonic adenomas, as a model of dysplasia. 4) Monitor the temporal and spatial extent of proliferation from medulloblastoma in post-natal ptc1 mice using the tabletop microscope. 5) Design and fabricate the miniaturized microscope using MEMS technology. 6) Monitor the temporal and spatial extent of proliferation from medulloblastoma in post-natal ptc1 knock-out mice and transplanted tumor cells using the miniaturized microscope. 7) Collect images from Barrett's epithelium and colonic adenomas during routine endoscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPTICAL BIOPSY USING OPTICAL COHERENCE TOMOGRAPHY Principal Investigator & Institution: Fujimoto, James G.; Professor of Pharmacology; Center for Cancer Research; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 05-SEP-1997; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract): This is a multidisciplinary collaborative program involving researchers at the Massachusetts Institute of Technology, Harvard Medical School, Massachusetts General Hospital, Brigham and Women's Hospital, and the National Cancer Institute. The hypothesis of this proposal is that optical coherence tomography (OCT), an emerging biomedical diagnostic imaging technology for in situ imaging of tissue microstructure, can be developed and applied for "optical biopsy," the real time, in vivo differentiation and monitoring of early neoplastic changes. This program integrates the development of new technology with its application to fundamental and clinical studies in oncology. The applicants propose to: 1. Develop ultrahigh resolution, spectroscopic, and Doppler OCT technology which extends the current 10-15 (m image resolution to the 1-2 (m level. This is a quantum leap in performance which will significantly improve imaging of architectural morphology and facilitate imaging of cellular features for identifying early neoplastic changes.

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Spectroscopic and Doppler OCT could enable functional imaging of tissue on a micron scale. 2. Develop delivery instruments for OCT which allow noninvasive or minimally invasive clinical imaging. These include a catheter/endoscope, colposcope, hysteroscope, hand held probe, and needle. 3. Investigate OCT imaging of early neoplastic changes and cancer progression in an animal model to define markers of dysplasia and to develop quantitative assessments of vascular density. A noninvasive, real time technique for quantitating angiogenesis can be a powerful research tool for the development of anti-angiogenesis agents. 4. Investigate OCT imaging in the female reproductive tract including the cervix and endometrium. The cervix is an excellent in vivo model system to establish markers of dysplastic change. Hysteroscopic OCT imaging of the uterus could improve the detection of endometrial dysplasia and cancer. 5. Investigate OCT imaging of dysplasia and leukoplakia of oral mucosa and chemoprevention treatment. Approaches to quantitatively assess response to chemoprevention would be important tools for pharmacological trials. 6. Investigate OCT imaging of the GI tract. Explore the feasibility of OCT for differentiating dysplasia and adenocarcinoma of the esophagus to guide conventional excisional biopsy and reduce false negative rates. Develop OCT as a low cost screening technique for Barrett's esophagus. Taken together, these studies will provide new imaging tools for oncology research and also develop new clinical diagnostic and screening techniques. 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

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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 •

Project Title: P53 AND DNA PLOIDY IN BARRETT'S METAPLASIA Principal Investigator & Institution: Younes, Mamoun; Associate Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 09-JAN-2001; Project End 31-DEC-2005 Summary: The goal of this study is to determinewhether the accuracy and costeffectiveness of endoscopic surveillance protocols aimed at detecting early malignant transformation in patients with Barrett's metaplasia (BM) can be improved by: 1) testing the hypothesis that p53 protein accumulation, DNA aneuploidy, and increased G0G1 or G2M fractions are more accurate and objective markers of malignant potential in Barrett's metaplasia (Barrett's esophagus) than the routine morphologic evaluation of dysplasia, 2) determining whether biopsy and cytology combined are more useful than either biopsy or cytology alone, 3) determining the time period that elapses between the appearance of LGD/IND, p53 protein accumulation, and DNA ploidy abnormalities, and between the development of high grade dysplasia (HGD) and adenocarcinoma (CA), and 4) perform cost-analysis to determine whether a surveillance program can be constructed in which biopsy and cytology are utilized in conjunction with p53 and DNA ploidy determination, and is less costly than current surveillance programs. Evaluation of p53 accumulation and DNA ploidy studies will be performed on initial and follow-up biopsies and brush cytology material from at least 200 patients with Barrett's metaplasia (BM). Step sections of biopsies (Bx) will be stained with hematoxylin and eosin, Feulgen stain for DNA quantitation, and immunostained for p53 protein, p53 gene mutational analysis will be performed by direct sequencing on microdissected tissues. Each case will be then analyzed for dysplasia, DNA ploidy patterns by image analysis, and p53 accumulation and gene mutation. Cytologic preparations (Cy) will be also evaluated for dysplasia, DNA ploidy patterns by image analysis, and p53 accumulation. The data will be compiled every two years and correlated with the patients outcome, using the development of HGD and CA as end points in separate analyses, and evaluated by univariate and multivariate analysis. The sensitivity, specificity, and positive and negative predictive value of each of these markers as predictors of HGD and of CA development will be determined separately on markers detected by Bx, Cy, and by the Bx and Cy combined. These will be compared to determine whether the use of both Bx and Cy in the follow-up of patients with BM is better than Bx or Cy alone. The time between the appearance of one of the markers and the development of carcinoma will also be studied, in order to identify a period of time in which close endoscopic surveillance is both clinically warranted and cost-effective. p53 mutations will be compared with p53 protein accumulation, and with DNA ploidy and patient outcome in order to determine if there are specific mutations associated with progression to DNA aneuploidy and CA. A multi step progression model will be constructed, upon which a new surveillance program will be proposed. A cost analysis will be then performed to determine whether a molecular based surveillance program would be more costeffective than current program which is based on morphologic grading of dysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHOTODYNAMIC THERAPY FOR ESOPHAGEAL MALIGNANCIES IN BARRETT'S ESOPHAGUS Principal Investigator & Institution: Wang, K K.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: With the increasing ability of non-invasive genetic tests to screen groups of patients at high risk of malignancy and the use of endoscopy to detect small malignancies of the gastrointestinal tract, the management of superficial neoplasma becomes more of a clinical dilemma. The small early carcinoma has traditionally been managed with surgical resection although this is associated with significant morbidity and mortality in the gastrointestinal tract especially the esophagus. Barrett's esophagus is a pre-malignant condition of the esophagus that has been diagnosed more frequently currently. The major issues involved in treating superficial neoplasma include accurate staging, type of therapy, and need for careful follow-up. The first major hurdle in implementing endoscopic therapy has been leaped with the development of endoscopic ultrasonography which allows the accurate staging of localized cancers. The second issue involves the ability of an endoscopic treatment to actually cure the primary malignancy which has been suggested based upon several preliminary studies. Photodynamic therapy has been shown to potentially ablate malignant esophageal tissue in 70% of patients treated. We propose to treat patients with superficial carcinomas within Barrett's esophagus who are not candidates for surgery using optimized photodynamic therapy. One of the major limitations to this therapy is predicting uniformity of results. We propose to control this therapy using novel methods. Drug dosimetry will be controlled using novel techniques include a fluorescence probe and a balloon centering device to control light dosimetry. After treatment, patients will be carefully followed to determine if malignant or dysplastic epithelium return. The patients will not only have standard biopsies but also cytology combined with image cytometry to detect the presence of malignancy and dysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHOTODYNAMIC THERAPY FOR THE ABLATION OF DYSPLASIA IN BARRETT'S ESOPHAGUS Principal Investigator & Institution: Sivak, Michael V.; Professor of Medicine & Chief, Division; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: It is anticipated that photodynamic therapy (PDT) using PHOTOFRIN at 2.0 mg/kg and a uniform laser light application will reduce the esophageal stricture rate seen and potentially reduce the intensity of the inflammatory reaction without compromising efficacy. The primary objective is to assess the efficacy of PDT with PHOTOFRIN (porfimer sodium) for injection plus omeprazole compared to omeprazole alone in the complete ablation of highgrade dysplasia in patients with Barrett's esophagus, in conjunction with a strict endoscopic surveillance and biopsy protocol. Ablation of HGD should confer a significant clinical benefit to the patient as it eliminates the immediate precursor to invasive cancer and removes the indication for esophagectomy which is associated with mortality and morbidity risks. The secondary objectives are to assess the safety and efficacy of PHOTOFRIN PDT plus omeprazole and systematic endoscopic surveillance compared to omeprazole therapy alone plus systematic endoscopic surveillance in terms of: quality of complete response; duration of

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complete response; delaying progression to cancer (time to progression); delaying the need for esophagectomy treatment failure; survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--GASTROINTESTINAL CANCER Principal Investigator & Institution: Haile, Robert W.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002 Summary: The overall goal of our Program is to conduct research on the causes, prevention, and therapy of gastrointestinal (GI) cancers. We aim to have a strong translational component to our research that is enhanced by a close integration of the basic sciences with clinical and epidemiological research. With respect to etiological research, primary areas of interest include: a) assessing the roles of putative candidate genes, such as NAT 1 and 2 in colorectal cancer; b) studying prevalence and determinants of epigenetic events, such as hypermethylation of the estrogen receptor5 gene promoter, in colorectal tumor samples; c) characterizing population-based parameters for genes already accepted as causes of these cancers such as the mismatch repair genes in colorectal cancer; and d) how environmental factors may interact with these genetic factors. With respect to clinical research, an emerging them in our Program is to identify and understand why cancer patients or subjects with selected precursor lesions, such as Barrett's esophagus or colorectal polyps, have differential responses to therapeutic interventions. Increasingly, we are using molecular markers to develop a profile of patients who do or do not respond to a given therapy. This type of research involves a close collaboration between molecular biologists, clinicians, and epidemiologists. It has obvious and strong translational potential, since one goal, already being realized in some of our management of patients with Barrett's esophagus, is to tailor a given intervention to a given patient based on their likelihood of responding. In addition, we have strength in hepatitis research and hepatology, with four clinical research centers at USC (Hepatitis, Hepatitis C Virus, Alcohol, NIDDK). Given this existing expertise, we believe we have the potential for an active research program in liver cancer, and have established an infrastructure with monthly meetings to develop a research program in this area. To further enhance our already substantial research program in GI cancer, we are focusing on two near-term goals: 1) even better integration across the basic, clinical, and population-based sciences, and 2) strengthening our capabilities to apply high volume molecular technologies to ongoing and planned studies. Members of the GI Program currently have over $10,000,0000 in research support. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RADIOFREQUENCY ABLATION OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Stern, Roger A.; Stellartech Research Corporation 1346 Bordeaux Dr Sunnyvale, Ca 94089 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The overall goal of this research program is to optimize and validate a novel endoscopic device to ablate high-grade dysplasia resulting from Barrett's esophagus, thereby preventing it from progressing to esophageal cancer. The Stellartech Coagulation System is a novel and proprietary device for ablating premalignant esophageal cells by delivering radio-frequency energy through a balloon catheter carrying an external electrode array. Energy delivery is

34


exquisitely controlled so that it kills only the dysplastic outer layer of cells without damaging the underlying muscle layer. Preliminary studies with a prototype device have demonstrated its safety and efficacy in a porcine model. In Phase I of this FastTrack SBIR-at-NIDDK project, we propose to: 1) design and test new geometric arrangements of the electrode array; 2) optimize treatment parameters to maximize the efficiency of ablation in a single treatment session; 3) conduct a preclinical safety study in pigs to demonstrate that the device is safe for testing in patients with Barrett's esophagus; and 4) evaluate real-time feedback systems to monitor treatment as an optional improvement to the device. Successful completion of these milestones will lead to the SBIR Phase II project to integrate the balloon catheter into a standard clinical endoscope and test its efficacy in a multi-center clinical trial of patients with high-grade Barrett's esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAMAN SPECTROSCOPY FOR CANCER DIAGNOSIS AND MONITORING Principal Investigator & Institution: Mourant, Judith R.; Professor; None; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2002; Project Start 08-MAY-2001; Project End 28-FEB-2006 Summary: (Verbatim from Applicant's Abstract): Our general objective is to enable the application of vibrational spectroscopy to cancer diagnosis and treatment monitoring. The detection of cancer at its earliest stages is crucial, for it greatly improves the likelihood of successful treatment. Traditional methods of diagnosis have relied on physical removal of a portion of tissue and microscopic assessment of morphology. The need for tissue removal reduces the area of tissue that can be sampled. A noninvasive technique would eliminate this problem. Furthermore, a noninvasive technique has the potential to allow treatment to begin during the same endoscopic procedure used for diagnosis and reduce other complications associated with tissue removal such as tissue handling and increased risk of infection to the patient. We will focus on developing Raman spectroscopy for detection of precancerous conditions in patients with Barrett's esophagus. Barrett's esophagus is a pathology in which the squamous epithelial lining is replaced by a specialized metaplastic epithelium and the likelihood of adenocarcinoma is increased. Because the microscopic changes of dysplasia are difficult to observe, the entire area of metaplastic epithelium should be sampled. Therefore, Barrett's esophagus is well-suited for a noninvasive diagnostic technique. The methods and techniques developed in this proposal may also find application in other tissues such as the cervix. The second goal of our work is to develop Raman spectroscopy as a method for assessing the effects of treatment. Current methods for monitoring the response of an individual tumor to therapy are unreliable and often difficult to implement during the course of therapy. Development of noninvasive or minimallyinvasive optical methods to reliably identify regions of apoptosis and necrosis would provide a simple method for assaying tumor response in each individual cancer patient. Consequently, treatments could be customized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REAL FLUORESCENCE

TIME

IN

VIVO

DIAGNOSIS

OF

DYSPLASIA

BY

Principal Investigator & Institution: Feld, Michael S.; Director; Center for Cancer Research; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 21-DEC-1990; Project End 31-MAR-2004

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Summary: The objective of this proposal is to develop and improve endoscopiccompatible spectroscopic techniques based on excitation-emission matrix (EEM) fluorescence, reflectance and light scattering for real-time in vivo analysis and diagnosis of dysplasia in the colon, esophagus and urinary bladder. We have developed three models to analyze tissue reflectance and fluorescence. The diffuse reflectance model furnishes information about tissue scatterers (such as mitochondria and the fiber network of connective tissue) and absorbers (such as hemoglobin). The light scattering spectroscopy (LSS) model yields information about nuclear size and crowding in the epithelial layer of tissue. The intrinsic fluorescence model isolates the contributions of fluorophores (such as structural proteins, NADH, porphyrins etc.) from the interference of absorbers and scatterers. Clinical EEM fluorescence/reflectance data will be collected for colonic adenoma, Barrett's esophagus and urothelial carcinoma, and will be analyzed using these models. Information about tissue structure and composition will be extracted and used to formulate new models and diagnostic algorithms. Validation of the algorithms will be performed prospectively with extended clinical data sets. In addition, we will extend the excitation wavelength range of our clinical EEM system down to 308 nm, to access more information about epithelial cellular proteins, update our data acquisition systems, and integrate data analysis software for real-time diagnosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINOID/RETINOID RECEPTOR IN ESOPHAGEAL CANCER RESPONS Principal Investigator & Institution: Xu, Xiaochun; Psychology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2004 Summary: The hypotheses to be tested in this revised proposal is that loss of nuclear retinoic acid receptor-beta (RAR-beta) may play an important role in esophageal carcinogenesis and that restoration of this receptor may enhance retinoid actions on HEC cells. The hypothesis will be tested by using both cultured HEC cells and tissue specimens. There are four specific aims: 1. To analyze the expression of RAR-beta2 and RXR-alpha in premalignant and malignant tissues from Barrett's esophagus and HEC patients and to find out whether there is an association between RAR-beta expression and the expression of COUP-TFs, Nur77, the cellular RA contents, and differentiation/ proliferation markers (cytokeratins, involucrin, cornifin, and Ki67) by using in situ hybridization with digoxigenin-labeled antisense riboprobes and immunohistochemistry. 2. To determine the expression of COUP-TFs and Nur77 in cultured HEC cells by Northern blot and Western blot and to investigate their relationship to RAR-beta expression by transcriptional activation assay, gel retardation assay, and immunoprecipitation followed by Western blotting. 3. To determine the roles of RAR-beta2, RAR-beta4 in regulating cell proliferation, differentiating, or apoptosis in HEC cells. Retroviral vectors containing sense or antisense RAR-beta2 or RAR-beta4 will be stably transinfected into HEC cells to overexpress the receptors in cells lacking constitutive receptor or block the expression of the endogenous receptor in cells expressing constitutive receptor. 4. To determine the effects of certain receptor-selective retinoids on the expression of RAR-beta2 and on proliferation, apoptosis, and differentiation markers (i.e., cytokeratin 1, involucrin, and cornifin, type I transglutaminase) in HEC cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 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

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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

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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: SCREENING FOR BARRETT'S IN OTOLARYNGOLOGY PATIENTS Principal Investigator & Institution: Jobe, Blair A.; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 30-NOV-2008 Summary: (provided by applicant): This application proposes a training program to develop Blair A. Jobe, MD into an independent clinician-scientist specializing in investigations of Barrett's esophagus and esophageal cancer. Dr. Jobe is a board certified General Surgeon with subspecialty training in laparoscopic and esophageal surgery. The mentored career development plan consists of a three-tiered approach: a didactic education resulting in a Masters in Clinical Investigation degree, a broad-based experiential learning program, and a mentored clinical research experience. The primary goal of this program will be for Dr. Jobe to achieve independence as a clinical investigator in all respects. Dr. Jobe is currently enrolled in the Human Investigations Program at Oregon Health and Science University (OHSU). This is a two year K30 (NIH) sponsored program for the purposes of developing patient-oriented research skills. Mentored research will be conducted under the direction of a mentorship committee composed of Dr. Cynthia Morris, Professor of Medical Informatics and Outcomes Research, OHSU, Dr. David Lieberman, Chief, Division of Gastroenterology, OHSU, and Dr. John Hunter, Chairman, Department of Surgery, OHSU. Dr. Jeffrey Peters from the University of Southern California will serve as an off-site mentor and committee member. The proposed research focuses on improving risk stratification for esophageal adenocarcinoma. The fact that most patients are unaware of the presence of Barrett's esophagus prior to cancer diagnosis and because a large proportion of these patients never develop heartburn or reflux, suggests that the current GERD symptom-based screening paradigm may be inadequate. We theorize that patients with extraesophageal reflux symptoms are at risk for unrecognized esophageal injury and thus Barrett's esophagus. We hypothesize that endoscopic screening of patients with extraesophageal reflux symptoms will reveal a significantly higher prevalence of Barrett's esophagus

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when compared to patients without symptoms of gastroesophageal reflux. The primary aim is to establish that patients with extraesophageal reflux symptoms who are referred to an otolaryngology clinic have a prevalence of Barrett's metaplasia equivalent to that of a population with GERD symptoms. A secondary aim is to establish that in-office unsedated small-caliber endoscopy is accurate and acceptable to patients when employed within a screening program for Barrett's esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPECTROSCOPIC DIAGNOSTIC FOR BARRETT'S DYSPLASIA Principal Investigator & Institution: Fulghum, Stephen F.; Newton Laboratories 247 Slade St Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 04-JUN-1999; Project End 29-SEP-2004 Summary: (provided by applicant): Barrett's esophagus (BE) is an acquired condition of the lower esophagus in which the normal squamous tissue is replaced by a metaplastic columnar mucosa. BE itself is not malignant, but it is the primary risk factor for esophageal adenocarcinoma, and a significant number of patients with BE will have adenocarcinoma at the time of first endoscopy. Currently, examination for dysplasia requires numerous random biopsy samples. This work will complete the development and clinically test an optical instrument for detecting and grading Barrett's dysplasia. Light scattering spectroscopy (LSS) has already been shown to differentiate between normal and diseased tissue conditions in BE patients, but the analysis is complex so the data is analyzed after the procedure is over. The instrument developed by this work will be based on white light LSS, but it will use a special probe design and data reduction algorithm, developed by NLI, enabling real-time results. The probe design makes use of the properties of light scattering by cell nuclei and other tissue components to enable the separation and subtraction of interfering effects, and the characterization of the nuclei, based on using spectral, angular, and polarization characteristics of the scattering processes. The tissue characterization follows from the instrument's quantitative determination of the nuclear size and number density for the surface mucosal cells - two properties commonly used by pathologists. Specifically, NLI will (i) produce the probe, (ii) calculate the data base for the real-time algorithm, (iii) produce the instrument with light source, spectrometer, and embedded computer (suitable for interface with a standard clinical video endoscope), (iv) verify the instrument operation in the laboratory using standard scattering materials, (v) verify the background subtraction properties by using normal and diseased resected colon tissue, and (vi) conduct clinical studies on patients with Barrett's Esophagus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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 “Barrett’s esophagus” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Barrett’s esophagus in the PubMed Central database: •

17p (p53) Allelic Losses, 4N(G2/tetraploid) Populations, and Progression to Aneuploidy in Barrett's Esophagus. by Galipeau PC, Cowan DS, Sanchez CA, Barrett MT, Emond MJ, Levine DS, Rabinovitch PS, Reid BJ.; 1996 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38939

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The utility of cytokeratins 7 and 20 (CK7/20) immunohistochemistry in the distinction of short-segment Barrett esophagus from gastric intestinal metaplasia: Is it reliable? by Kurtkaya-Yapicier O, Gencosmanoglu R, Avsar E, Bakirci N, Tozun N, Sav A.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=305372

3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Barrett’s esophagus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Barrett’s esophagus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Barrett’s esophagus (hyperlinks lead to article summaries): •

A predictive model for length of Barrett's esophagus with hiatal hernia length and duration of esophageal acid exposure. Author(s): Wakelin DE, Al-Mutawa T, Wendel C, Green C, Garewal HS, Fass R. Source: Gastrointestinal Endoscopy. 2003 September; 58(3): 350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528207&dopt=Abstract

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A survey of Canadian gastroenterologists about the management of Barrett's esophagus. Author(s): MacNeil-Covin L, Casson AG, Malatjalian D, Veldhuyzen van Zanten S. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 May; 17(5): 313-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772005&dopt=Abstract

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Accuracy of EUS in the evaluation of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma. Author(s): Scotiniotis IA, Kochman ML, Lewis JD, Furth EE, Rosato EF, Ginsberg GG. Source: Gastrointestinal Endoscopy. 2001 December; 54(6): 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726843&dopt=Abstract

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Accuracy of magnifying endoscopy with methylene blue in the diagnosis of specialized intestinal metaplasia and short-segment Barrett's esophagus in Japanese patients without Helicobacter pylori infection. Author(s): Yagi K, Nakamura A, Sekine A. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872084&dopt=Abstract

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

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Acid and bile reflux in Barrett's esophagus: a tale of two evils. Author(s): Triadafilopoulos G. Source: Gastroenterology. 2001 December; 121(6): 1502-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729130&dopt=Abstract

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Acid- and bile-induced PGE(2) release and hyperproliferation in Barrett's esophagus are COX-2 and PKC-epsilon dependent. Author(s): Kaur BS, Triadafilopoulos G. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2002 August; 283(2): G327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121879&dopt=Abstract

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Acid exposure activates the mitogen-activated protein kinase pathways in Barrett's esophagus. Author(s): Souza RF, Shewmake K, Terada LS, Spechler SJ. Source: Gastroenterology. 2002 February; 122(2): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832445&dopt=Abstract

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Acid suppression therapy for Barrett's esophagus. Author(s): Spechler SJ. Source: Eur J Surg Suppl. 2001; (586): 78-81. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718531&dopt=Abstract

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Acid suppression therapy in Barrett's esophagus: the importance of pH monitoring. Author(s): Castell DO. Source: Current Gastroenterology Reports. 2000 June; 2(3): 173-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10957927&dopt=Abstract

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Adenosquamous carcinoma arising in Barrett's esophagus. Author(s): Noguchi T, Uchida Y, Fumoto S, Wada S, Sato T, Takeno S. Source: Jpn J Thorac Cardiovasc Surg. 2002 December; 50(12): 537-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561099&dopt=Abstract

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Allelic imbalance of 7q32.3-q36.1 during tumorigenesis in Barrett's esophagus. Author(s): Riegman PH, Burgart LJ, Wang KK, Wink-Godschalk JC, Dinjens WN, Siersema PD, Tilanus HW, van Dekken H. Source: Cancer Research. 2002 March 1; 62(5): 1531-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888931&dopt=Abstract

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Aminolevulinic acid-induced photodynamic therapy: safe and effective ablation of dysplasia in Barrett's esophagus. Author(s): Ackroyd R, Brown NJ, Davis MF, Stephenson TJ, Stoddard CJ, Reed MW. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(1): 18-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005326&dopt=Abstract

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Angiogenic markers, neovascularization and malignant deformation of Barrett's esophagus. Author(s): Wilson KT. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(1): 16-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060038&dopt=Abstract

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Antireflux surgery, highly selective vagotomy and duodenal switch procedure: postoperative evaluation in patients with complicated and non-complicated Barrett's esophagus. Author(s): Braghetto I, Csendes A, Burdiles P, Korn O. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005325&dopt=Abstract

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Apoptosis and cell proliferation in the metaplasia-dysplasia-carcinoma-sequence of Barrett's esophagus. Author(s): Halm U, Tannapfel A, Breitung B, Breidert M, Wittekind CW, Mossner J. Source: Hepatogastroenterology. 2000 July-August; 47(34): 962-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11020858&dopt=Abstract

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Appearance and prognosis of dysplasia in Barrett's esophagus. Author(s): Sampliner RE. Source: Chest Surg Clin N Am. 2002 February; 12(1): 69-76, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901934&dopt=Abstract

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Are ulcers a marker for invasive carcinoma in Barrett's esophagus? Data from a diagnostic variability study with clinical follow-up. Author(s): Montgomery E, Bronner MP, Greenson JK, Haber MM, Hart J, Lamps LW, Lauwers GY, Lazenby AJ, Lewin DN, Robert ME, Washington K, Goldblum JR. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808966&dopt=Abstract

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Argon plasma coagulation in Barrett's esophagus. Author(s): Franchimont D, Van Laethem JL, Deviere J. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 457-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629102&dopt=Abstract

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Artificial neural networks and gene filtering distinguish between global gene expression profiles of Barrett's esophagus and esophageal cancer. Author(s): Xu Y, Selaru FM, Yin J, Zou TT, Shustova V, Mori Y, Sato F, Liu TC, Olaru A, Wang S, Kimos MC, Perry K, Desai K, Greenwald BD, Krasna MJ, Shibata D, Abraham JM, Meltzer SJ. Source: Cancer Research. 2002 June 15; 62(12): 3493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067993&dopt=Abstract

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Association of metallothionein expression and lack of apoptosis with progression of carcinogenesis in Barrett's esophagus. Author(s): Li Y, Wo JM, Cai L, Zhou Z, Rosenbaum D, Mendez C, Ray MB, Jones WF, Kang YJ. Source: Experimental Biology and Medicine (Maywood, N.J.). 2003 March; 228(3): 28692. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626773&dopt=Abstract

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Barrett's esophagus and heater probe. Author(s): Michopoulos S. Source: Gastroenterology. 2003 June; 124(7): 2008-9; Author Reply 2009. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812203&dopt=Abstract

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Barrett's esophagus can and does regress after antireflux surgery: a study of prevalence and predictive features. Author(s): Gurski RR, Peters JH, Hagen JA, DeMeester SR, Bremner CG, Chandrasoma PT, DeMeester TR. Source: Journal of the American College of Surgeons. 2003 May; 196(5): 706-12; Discussion 712-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742201&dopt=Abstract

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Barrett's esophagus evokes a quantitatively and qualitatively altered response to both acid and hypertonic solutions. Author(s): Fletcher J, Gillen D, Wirz A, McColl KE. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1480-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873566&dopt=Abstract

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Barrett's esophagus prevalence and epidemiology. Author(s): Tutuian R, Castell DO. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 227-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916656&dopt=Abstract

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Barrett's esophagus seen in new photodynamic light. Author(s): Morrow T. Source: Manag Care. 2003 August; 12(8): 44-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966852&dopt=Abstract

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Barrett's esophagus. Author(s): Ertan A, Younes M. Source: Digestive Diseases and Sciences. 2000 August; 45(8): 1670-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007123&dopt=Abstract

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Barrett's esophagus. Author(s): Csendes A. Source: Journal of the American College of Surgeons. 2003 November; 197(5): 882-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585434&dopt=Abstract

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Barrett's esophagus. Author(s): Cohen JT, Postma GN, Enriquez PS, Koufman JA. Source: Ear, Nose, & Throat Journal. 2003 June; 82(6): 422. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861864&dopt=Abstract

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Barrett's esophagus. Author(s): Kollar T, Majek J, Slezak P, Makovnik P, Mlkvy P. Source: Bratisl Lek Listy. 2003; 104(2): 87-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839220&dopt=Abstract

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Barrett's esophagus: a review. Author(s): Gadour M, Ayoola EA. Source: Trop Gastroenterol. 2002 October-December; 23(4): 157-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833699&dopt=Abstract

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Barrett's esophagus: a surgical disease? Author(s): Lord RV, Bowrey DJ, Blom D. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3302-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095361&dopt=Abstract

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Barrett's esophagus: ablative endoscopic techniques. Author(s): Spinelli P, Falsitta M. Source: Tumori. 2003 March-April; 89(2): 117-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841655&dopt=Abstract

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Barrett's esophagus: an update. Author(s): Conio M, Lapertosa G, Blanchi S, Filiberti R. Source: Critical Reviews in Oncology/Hematology. 2003 May; 46(2): 187-206. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711361&dopt=Abstract

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Barrett's esophagus: chemoprevention. Author(s): Souza RF, Spechler SJ. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 419-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629099&dopt=Abstract

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Barrett's esophagus: current status of treatment. Author(s): Schuchert MJ, Luketich JD. Source: Adv Surg. 2003; 37: 179-96. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953633&dopt=Abstract

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Barrett's esophagus: endoscopic resection. Author(s): Pech O, May A, Gossner L, Ell C. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 505-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629106&dopt=Abstract

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Barrett's esophagus: patient information and the Internet. The patient's perspective. Author(s): Gough MD, Gilliam AD, Stoddard CJ, Ackroyd R. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2003; 16(2): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823197&dopt=Abstract

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Barrett's esophagus: the long and the short of it. Author(s): Lewis JD. Source: Gastroenterology. 2000 October; 119(4): 1165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040204&dopt=Abstract

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Bile and acid reflux in long and short segment Barrett's esophagus, and in reflux disease. Author(s): Pfaffenbach B, Hullerum J, Orth KH, Langer M, Stabenow-Lohbauer U, Lux G. Source: Zeitschrift Fur Gastroenterologie. 2000 July; 38(7): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10965553&dopt=Abstract

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Biomarkers in Barrett's esophagus. Author(s): Reid BJ, Blount PL, Rabinovitch PS. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 369-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916666&dopt=Abstract

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CagA-positive strains of Helicobacter pylori may protect against Barrett's esophagus. Author(s): Vaezi MF, Falk GW, Peek RM, Vicari JJ, Goldblum JR, Perez-Perez GI, Rice TW, Blaser MJ, Richter JE. Source: The American Journal of Gastroenterology. 2000 September; 95(9): 2206-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007219&dopt=Abstract

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Cancer risk and Barrett's esophagus. Author(s): Kelty CJ, Ackroyd R. Source: The American Journal of Medicine. 2002 April 15; 112(6): 507. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959070&dopt=Abstract

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Case report: esophageal collision tumor (oat cell carcinoma and adenocarcinoma) in Barrett's esophagus: immunohistochemical, electron microscopy and LOH analysis. Author(s): Gonzalez LM, Sanz-Esponera J, Saez C, Alvarez T, Sierra E, Sanz-Ortega J. Source: Histology and Histopathology. 2003 January; 18(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507278&dopt=Abstract

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Characteristics of acid reflux in Barrett's esophagus. Author(s): Xu J, Chen J, Hou X. Source: J Huazhong Univ Sci Technolog Med Sci. 2002; 22(3): 235-6, 264. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658814&dopt=Abstract

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Characterization of dysplastic tissue morphology and biochemistry in Barrett's esophagus using diffuse reflectance and light scattering spectroscopy. Author(s): Georgakoudi I, Van Dam J. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 297-308. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916661&dopt=Abstract

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Chromoendoscopy and magnification endoscopy in Barrett's esophagus. Author(s): Connor MJ, Sharma P. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 269-77. Review. Erratum In: Gastrointest Endosc Clin N Am. 2003 July; 13(3): Ix. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916659&dopt=Abstract

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Chromoscopy of intestinal metaplasia in Barrett's esophagus. Author(s): Canto MI, Yoshida T, Gossner L. Source: Endoscopy. 2002 April; 34(4): 330-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932792&dopt=Abstract

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Circumferential EMR and complete removal of Barrett's epithelium: a new approach to management of Barrett's esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma. Author(s): Seewald S, Akaraviputh T, Seitz U, Brand B, Groth S, Mendoza G, He X, Thonke F, Stolte M, Schroeder S, Soehendra N. Source: Gastrointestinal Endoscopy. 2003 June; 57(7): 854-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776032&dopt=Abstract

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Circumferential EMR of carcinoma arising in Barrett's esophagus: case report. Author(s): Satodate H, Inoue H, Yoshida T, Usui S, Iwashita M, Fukami N, Shiokawa A, Kudo SE. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872107&dopt=Abstract

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Clinical and histologic follow-up after antireflux surgery for Barrett's esophagus. Author(s): Bowers SP, Mattar SG, Smith CD, Waring JP, Hunter JG. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 July-August; 6(4): 532-8; Discussion 539. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127118&dopt=Abstract

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Clinical and pathologic response of Barrett's esophagus to laparoscopic antireflux surgery. Author(s): Oelschlager BK, Barreca M, Chang L, Oleynikov D, Pellegrini CA. Source: Annals of Surgery. 2003 October; 238(4): 458-64; Discussion 464-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530718&dopt=Abstract

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Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia. Author(s): Csendes A, Smok G, Quiroz J, Burdiles P, Rojas J, Castro C, Henriquez A. Source: The American Journal of Gastroenterology. 2002 March; 97(3): 554-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922546&dopt=Abstract

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Coexistent multiple adenocarcinomas arising in Barrett's esophagus 23 years after total gastrectomy and esophageal small cell carcinoma. Author(s): Noguchi T, Takeno S, Sato T, Uchida Y, Daa T, Yokoyama S. Source: Jpn J Thorac Cardiovasc Surg. 2003 June; 51(6): 259-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831243&dopt=Abstract

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Colonization with cagA-positive Helicobacter pylori strains inversely associated with reflux esophagitis and Barrett's esophagus. Author(s): Loffeld RJ, Werdmuller BF, Kuster JG, Perez-Perez GI, Blaser MJ, Kuipers EJ. Source: Digestion. 2000; 62(2-3): 95-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11025356&dopt=Abstract

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Communicating esophageal duplication with Barrett's esophagus and high-grade dysplasia. Author(s): Jobe BA, Baumann HW, Domreis JS, Sheppard BC. Source: Surgery. 2002 July; 132(1): 112-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110808&dopt=Abstract

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Cost-effectiveness of photodynamic therapy for treatment of Barrett's esophagus with high grade dysplasia. Author(s): Hur C, Nishioka NS, Gazelle GS. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1273-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870783&dopt=Abstract

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Cyclooxygenase-2 inhibitor therapy for the prevention of esophageal adenocarcinoma in Barrett's esophagus. Author(s): Gupta RA, DuBois RN. Source: Journal of the National Cancer Institute. 2002 March 20; 94(6): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904306&dopt=Abstract

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Cytokeratin and DAS-1 immunostaining reveal similarities among cardiac mucosa, CIM, and Barrett's esophagus. Author(s): DeMeester SR, Wickramasinghe KS, Lord RV, Friedman A, Balaji NS, Chandrasoma PT, Hagen JA, Peters JH, DeMeester TR. Source: The American Journal of Gastroenterology. 2002 October; 97(10): 2514-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385432&dopt=Abstract

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Cytokeratin immunoreactivity patterns in the diagnosis of short-segment Barrett's esophagus. Author(s): Ormsby AH, Vaezi MF, Richter JE, Goldblum JR, Rice TW, Falk GW, Gramlich TL. Source: Gastroenterology. 2000 September; 119(3): 683-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982762&dopt=Abstract

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Cytology in Barrett's esophagus. Author(s): Falk GW. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 335-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916664&dopt=Abstract

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DDW reports 2003 Orlando: reflux disease and Barrett's esophagus. Author(s): Rosch T. Source: Endoscopy. 2003 October; 35(10): 809-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551857&dopt=Abstract

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Decreased expression of Fas (CD95/APO1) associated with goblet cell metaplasia in Barrett's esophagus. Author(s): Younes M, Lechago J, Ertan A, Finnie D, Younes A. Source: Human Pathology. 2000 April; 31(4): 434-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821489&dopt=Abstract

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Detection of Barrett's esophagus superimposed by esophageal cancer by FDG positron emission tomography. Author(s): Neto CA, Zhuang H, Ghesani N, Alavi A. Source: Clinical Nuclear Medicine. 2001 December; 26(12): 1060. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711724&dopt=Abstract

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Detection of high-grade dysplasia in Barrett's esophagus by spectroscopy measurement of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Author(s): Brand S, Wang TD, Schomacker KT, Poneros JM, Lauwers GY, Compton CC, Pedrosa MC, Nishioka NS. Source: Gastrointestinal Endoscopy. 2002 October; 56(4): 479-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297761&dopt=Abstract

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Detection of preinvasive cancer cells: early-warning changes in precancerous epithelial cells can now be spotted in situ and Endoscopic detection of dysplasia in patients with Barrett's esophagus using light-scattered spectroscopy. Author(s): Pfau P, Chak A. Source: Gastrointestinal Endoscopy. 2001 September; 54(3): 414-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550671&dopt=Abstract

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Development of Barrett's esophagus after 'spontaneous' healing of atrophic corpus gastritis. Author(s): Kokkola A, Sipponen P, Haapiainen R, Rautelin H, Karjalainen-Lindsberg ML, Puolakkainen P. Source: Helicobacter. 2003 December; 8(6): 590-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14632673&dopt=Abstract

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Diagnosing and managing Barrett's esophagus. Author(s): Sampliner RE. Source: Am J Manag Care. 2000 October; 6(16 Suppl): S886-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184660&dopt=Abstract

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Diagnosis of Barrett's esophagus using optical coherence tomography. Author(s): Poneros JM, Nishioka NS. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 309-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916662&dopt=Abstract

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Diagnostic inconsistencies in Barrett's esophagus. Department of Veterans Affairs Gastroesophageal Reflux Study Group. Author(s): Kim SL, Waring JP, Spechler SJ, Sampliner RE, Doos WG, Krol WF, Williford WO. Source: Gastroenterology. 1994 October; 107(4): 945-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7926484&dopt=Abstract

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Discussion on preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systemic review. Author(s): Gough M, Kelty C, Bird N, Majeed A, Ackroyd R. Source: Gastroenterology. 2002 September; 123(3): 955; Discussion 955. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198729&dopt=Abstract

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Does a surgical antireflux procedure decrease the incidence of esophageal adenocarcinoma in Barrett's esophagus? A meta-analysis. Author(s): Corey KE, Schmitz SM, Shaheen NJ. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2390-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638338&dopt=Abstract

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Does acid suppression alter progression in Barrett's esophagus? Author(s): Castell DO. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 213-4; Author Reply 214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526966&dopt=Abstract

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Does chemoprevention of Barrett's esophagus using acid suppression and/or COX-2 inhibition prevent neoplastic progression? Author(s): Fennerty MB. Source: Reviews in Gastroenterological Disorders. 2002; 2 Suppl 2: S30-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478242&dopt=Abstract

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Does Helicobacter pylori always represent a peaceful host of Barrett's esophagus? Author(s): Ierardi E, Burattini O, Marangi S, Panarese A, Francavilla A, Monno R. Source: Journal of Clinical Gastroenterology. 2001 November-December; 33(5): 424-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606865&dopt=Abstract

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Does methylene blue detect intestinal metaplasia in Barrett's esophagus? Author(s): Breyer HP, Silva De Barros SG, Maguilnik I, Edelweiss MI. Source: Gastrointestinal Endoscopy. 2003 April; 57(4): 505-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665760&dopt=Abstract

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Does surveillance endoscopy improve life expectancy in those with Barrett's esophagus? Author(s): Shaheen NJ. Source: Gastroenterology. 2001 December; 121(6): 1516-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729134&dopt=Abstract

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Duodenogastroesophageal reflux: relationship to pH and importance in Barrett's esophagus. Author(s): Champion G, Richter JE, Vaezi MF, Singh S, Alexander R. Source: Gastroenterology. 1994 September; 107(3): 747-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8076761&dopt=Abstract

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Dysplasia and adenocarcinoma after classic antireflux surgery in patients with Barrett's esophagus: the need for long-term subjective and objective follow-up. Author(s): Csendes A, Burdiles P, Braghetto I, Smok G, Castro C, Korn O, Henriquez A. Source: Annals of Surgery. 2002 February; 235(2): 178-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807356&dopt=Abstract

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Dysplasia arising in barrett's esophagus: diagnostic pitfalls and natural history. Author(s): Goldblum JR, Lauwers GY. Source: Semin Diagn Pathol. 2002 February; 19(1): 12-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936261&dopt=Abstract

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Dysplasia in barrett's esophagus. New techniques and markers. Author(s): Guindi M, Riddell RH. Source: Chest Surg Clin N Am. 2002 February; 12(1): 59-68, Viii-Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901933&dopt=Abstract

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Early and late results of the acid suppression and duodenal diversion operation in patients with barrett's esophagus: analysis of 210 cases. Author(s): Csendes A, Burdiles P, Braghetto I, Korn O, Diaz JC, Rojas J. Source: World Journal of Surgery. 2002 May; 26(5): 566-76. Epub 2002 March 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098047&dopt=Abstract

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Effect of duodenal diversion on low-grade dysplasia in patients with Barrett's esophagus: analysis of 37 patients. Author(s): Csendes A, Smok G, Burdiles P, Braghetto I, Castro C, Korn O. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 July-August; 6(4): 645-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127135&dopt=Abstract

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Effect of multipolar electrocoagulation on EUS findings in Barrett's esophagus. Author(s): Faigel DO, Lieberman DA, Weinstein WM, Fanning S, Fennerty MB, Sampliner RB. Source: Gastrointestinal Endoscopy. 2002 January; 55(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756909&dopt=Abstract

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Efficacy of laparoscopic antireflux surgery in patients with Barrett's esophagus. Author(s): Desai KM, Soper NJ, Frisella MM, Quasebarth MA, Dunnegan DL, Brunt LM. Source: American Journal of Surgery. 2003 December; 186(6): 652-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672774&dopt=Abstract

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Endoscopic ablation of Barrett's esophagus using argon plasma coagulation (APC) following surgical laparoscopic fundoplication. Author(s): Morino M, Rebecchi F, Giaccone C, Taraglio S, Sidoli L, Ferraris R. Source: Surgical Endoscopy. 2003 April; 17(4): 539-42. Epub 2003 February 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582755&dopt=Abstract

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Endoscopic ablation of Barrett's esophagus. Author(s): Fennerty MB. Source: Current Gastroenterology Reports. 1999 June; 1(3): 210-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980951&dopt=Abstract

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Endoscopic detection of dysplasia in patients with Barrett's esophagus using lightscattering spectroscopy. Author(s): Wallace MB, Perelman LT, Backman V, Crawford JM, Fitzmaurice M, Seiler M, Badizadegan K, Shields SJ, Itzkan I, Dasari RR, Van Dam J, Feld MS. Source: Gastroenterology. 2000 September; 119(3): 677-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982761&dopt=Abstract

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Endoscopic diagnosis and surveillance of Barrett's esophagus. Author(s): Fennerty MB. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 257-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916658&dopt=Abstract

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Endoscopic fluorescence detection of intraepithelial neoplasia in Barrett's esophagus after oral administration of aminolevulinic acid. Author(s): Stepinac T, Felley C, Jornod P, Lange N, Gabrecht T, Fontolliet C, Grosjean P, vanMelle G, van den Bergh H, Monnier P, Wagnieres G, Dorta G. Source: Endoscopy. 2003 August; 35(8): 663-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929061&dopt=Abstract

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Endoscopic mucosal resection for lesions with endoscopic features suggestive of malignancy and high-grade dysplasia within Barrett's esophagus. Author(s): Nijhawan PK, Wang KK. Source: Gastrointestinal Endoscopy. 2000 September; 52(3): 328-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968845&dopt=Abstract

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Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus. Author(s): Sharma P. Source: Gastrointestinal Endoscopy. 2002 January; 55(1): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789480&dopt=Abstract

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Endoscopic resection of adenocarcinoma arising in a tongue of Barrett's esophagus. Author(s): Harada M, Nagashima R, Takeda H, Takahashi T. Source: Gastrointestinal Endoscopy. 2000 September; 52(3): 427-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968868&dopt=Abstract

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Endoscopic screening and surveillance for Barrett's esophagus: can claims data determine its effectiveness? Author(s): Cooper GS. Source: Gastrointestinal Endoscopy. 2003 June; 57(7): 914-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776041&dopt=Abstract

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Endoscopy in Barrett's esophagus. Surveillance during reflux management and new advances in the diagnosis and early detection of dysplasia. Author(s): el Khoury J, Sahai AV. Source: Chest Surg Clin N Am. 2002 February; 12(1): 47-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901932&dopt=Abstract

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Enhanced magnification endoscopy: a new technique to identify specialized intestinal metaplasia in Barrett's esophagus. Author(s): Guelrud M, Herrera I, Essenfeld H, Castro J. Source: Gastrointestinal Endoscopy. 2001 May; 53(6): 559-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323579&dopt=Abstract

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Epidemiology and significance of Barrett's esophagus. Author(s): DeVault KR. Source: Digestive Diseases (Basel, Switzerland). 2000-2001; 18(4): 195-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356990&dopt=Abstract

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Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett's esophagus. Author(s): Dixon J, Strugala V, Griffin SM, Welfare MR, Dettmar PW, Allen A, Pearson JP. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2575-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569678&dopt=Abstract

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Experimental Barrett's esophagus and the origin of intestinal metaplasia. Author(s): Pera M, Pera M. Source: Chest Surg Clin N Am. 2002 February; 12(1): 25-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901930&dopt=Abstract

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Extended lifespan of Barrett's esophagus epithelium transduced with the human telomerase catalytic subunit: a useful in vitro model. Author(s): Palanca-Wessels MC, Klingelhutz A, Reid BJ, Norwood TH, Opheim KE, Paulson TG, Feng Z, Rabinovitch PS. Source: Carcinogenesis. 2003 July; 24(7): 1183-90. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807723&dopt=Abstract

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Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma. Author(s): Buttar NS, Wang KK, Sebo TJ, Riehle DM, Krishnadath KK, Lutzke LS, Anderson MA, Petterson TM, Burgart LJ. Source: Gastroenterology. 2001 June; 120(7): 1630-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375945&dopt=Abstract

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Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett's esophagus. Author(s): Kiraly A, Suto G, Czimmer J, Horvath OP, Mozsik G. Source: Journal of Physiology, Paris. 2001 January-December; 95(1-6): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595437&dopt=Abstract

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Familial aggregation of gastroesophageal reflux in patients with Barrett's esophagus and esophageal adenocarcinoma. Author(s): Romero Y, Cameron AJ, Locke GR 3rd, Schaid DJ, Slezak JM, Branch CD, Melton LJ 3rd. Source: Gastroenterology. 1997 November; 113(5): 1449-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9352846&dopt=Abstract

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Familial Barrett's esophagus associated with adenocarcinoma. Author(s): Jochem VJ, Fuerst PA, Fromkes JJ. Source: Gastroenterology. 1992 April; 102(4 Pt 1): 1400-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1551547&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901927&dopt=Abstract

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Familial gastroesophageal reflux and development of Barrett's esophagus. Author(s): Crabb DW, Berk MA, Hall TR, Conneally PM, Biegel AA, Lehman GA. Source: Annals of Internal Medicine. 1985 July; 103(1): 52-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4003988&dopt=Abstract

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Familial visceral myopathy with pseudo-obstruction, megaduodenum, Barrett's esophagus, and cardiac abnormalities. Author(s): Mungan Z, Akyuz F, Bugra Z, Yonall O, Ozturk S, Acar A, Cevikbas U. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2556-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638363&dopt=Abstract

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Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Author(s): Eads CA, Lord RV, Kurumboor SK, Wickramasinghe K, Skinner ML, Long TI, Peters JH, DeMeester TR, Danenberg KD, Danenberg PV, Laird PW, Skinner KA. Source: Cancer Research. 2000 September 15; 60(18): 5021-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11016622&dopt=Abstract

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Flow cytometric DNA analysis and p53 protein expression show a good correlation with histologic findings in patients with Barrett's esophagus. Author(s): Gimenez A, Minguela A, Parrilla P, Bermejo J, Perez D, Molina J, Garcia AM, Ortiz MA, Alvarez R, de Haro LM. Source: Cancer. 1998 August 15; 83(4): 641-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9708926&dopt=Abstract

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Flow cytometry and Barrett's esophagus. Author(s): Herman RD, McKinley MJ, Bronzo RL, Weissman GS, Goldman IS, Kahn E, Stiel L. Source: Digestive Diseases and Sciences. 1992 April; 37(4): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1551359&dopt=Abstract

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Flow cytometry and dysplasia in Barrett's esophagus. Author(s): Lev R. Source: Gastroenterology. 1990 April; 98(4): 1107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2311871&dopt=Abstract

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Flow cytometry in Barrett's esophagus. What have we learned so far? Author(s): Garewal HS, Sampliner RE, Fennerty MB. Source: Digestive Diseases and Sciences. 1991 May; 36(5): 548-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2022154&dopt=Abstract

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Flow cytometry in Barrett's esophagus: when all is said and done, more is said than done! Author(s): Fennerty MB, Sampliner RE. Source: The American Journal of Gastroenterology. 1993 February; 88(2): 319-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8424444&dopt=Abstract

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Flow-cytometric and histological progression to malignancy in Barrett's esophagus: prospective endoscopic surveillance of a cohort. Author(s): Reid BJ, Blount PL, Rubin CE, Levine DS, Haggitt RC, Rabinovitch PS. Source: Gastroenterology. 1992 April; 102(4 Pt 1): 1212-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1551528&dopt=Abstract

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Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus. Author(s): Georgakoudi I, Jacobson BC, Van Dam J, Backman V, Wallace MB, Muller MG, Zhang Q, Badizadegan K, Sun D, Thomas GA, Perelman LT, Feld MS. Source: Gastroenterology. 2001 June; 120(7): 1620-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375944&dopt=Abstract

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Follow-up for high-grade dysplasia in Barrett's esophagus. Author(s): Kara MA, Bergman JJ, Tytgat GN. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 513-33, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629107&dopt=Abstract

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Functional foregut abnormalities in Barrett's esophagus. Author(s): Stein HJ, Hoeft S, DeMeester TR. Source: The Journal of Thoracic and Cardiovascular Surgery. 1993 January; 105(1): 10711. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8419690&dopt=Abstract

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Fundic patch operation in the treatment of esophageal stricture with Barrett's esophagus--a case report. Author(s): Watanabe M, Nakamura R, Nishinari N, Sugimura Y, Kondo M, Saito K, Mori S. Source: Jpn J Surg. 1987 November; 17(6): 533-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3437625&dopt=Abstract

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Fundoplication provides effective and durable symptom relief in patients with Barrett's esophagus. Author(s): Farrell TM, Smith CD, Metreveli RE, Johnson AB, Galloway KD, Hunter JG. Source: American Journal of Surgery. 1999 July; 178(1): 18-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10456696&dopt=Abstract

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Gastric metaplasia of the proximal esophagus associated with esophageal adenocarcinoma and Barrett's esophagus: what is the connection? Inlet patch revisited. Author(s): Malhi-Chowla N, Ringley RK, Wolfsen HC. Source: Digestive Diseases (Basel, Switzerland). 2000; 18(3): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279338&dopt=Abstract

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Gastric surgery and Barrett's esophagus. Author(s): Parrilla P. Source: Gastroenterology. 2002 September; 123(3): 954. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198728&dopt=Abstract

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Gastric surgery does not increase the risk of developing Barrett's esophagus. Author(s): Parrilla P, Liron R, Martinez de Haro LF, Ortiz A, Molina J, De Andres B. Source: The American Journal of Gastroenterology. 1997 June; 92(6): 960-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9177510&dopt=Abstract

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Gastric surgery is not a risk for Barrett's esophagus or esophageal adenocarcinoma. Author(s): Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Source: Gastroenterology. 2001 December; 121(6): 1281-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729106&dopt=Abstract

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Gastrin-induced hyperproliferation in Barrett's esophagus. Author(s): Fitzgerald RC, Abdalla S. Source: Gastroenterology. 2003 December; 125(6): 1921; Author Reply 1921-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14727639&dopt=Abstract

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Gastroesophageal reflux disease and Barrett's esophagus. Author(s): Rosch T. Source: Endoscopy. 2000 November; 32(11): 826-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085470&dopt=Abstract

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Gastroesophageal reflux disease and Barrett's esophagus. Author(s): Katzka DA, Rustgi AK. Source: The Medical Clinics of North America. 2000 September; 84(5): 1137-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11026922&dopt=Abstract

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Gastroesophageal reflux disease and Barrett's esophagus. Author(s): Koop H. Source: Endoscopy. 2002 February; 34(2): 97-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822004&dopt=Abstract

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Gastroesophageal reflux disease and Barrett's esophagus. Author(s): Rosch T. Source: Endoscopy. 2001 November; 33(11): 909-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668398&dopt=Abstract

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Gastroesophageal reflux disease and Barrett's esophagus. Author(s): Falk GW. Source: Endoscopy. 2001 February; 33(2): 109-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272213&dopt=Abstract

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Gastrointestinal tissue polyamine contents of patients with Barrett's esophagus treated with alpha-difluoromethylornithine. Author(s): Gerner EW, Garewal HS, Emerson SS, Sampliner RE. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1994 June; 3(4): 325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8061581&dopt=Abstract

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Genetic alterations in Barrett's esophagus and esophageal adenocarcinoma. Author(s): Dinjens WN. Source: Minerva Chir. 2002 December; 57(6): 733-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592217&dopt=Abstract

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Genetic differences between adenocarcinomas arising in Barrett's esophagus and gastric mucosa. Author(s): El-Rifai W, Frierson HF Jr, Moskaluk CA, Harper JC, Petroni GR, Bissonette EA, Jones DR, Knuutila S, Powell SM. Source: Gastroenterology. 2001 September; 121(3): 592-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522743&dopt=Abstract

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Genomic alterations in malignant transformation of Barrett's esophagus. Author(s): Riegman PH, Vissers KJ, Alers JC, Geelen E, Hop WC, Tilanus HW, van Dekken H. Source: Cancer Research. 2001 April 1; 61(7): 3164-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306503&dopt=Abstract

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GERD, DGER, or both in Barrett's esophagus? Author(s): Sharma P, Sampliner R. Source: The American Journal of Gastroenterology. 1997 May; 92(5): 903-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9149216&dopt=Abstract

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Global gene expression profiling in Barrett's esophagus and esophageal cancer: a comparative analysis using cDNA microarrays. Author(s): Selaru FM, Zou T, Xu Y, Shustova V, Yin J, Mori Y, Sato F, Wang S, Olaru A, Shibata D, Greenwald BD, Krasna MJ, Abraham JM, Meltzer SJ. Source: Oncogene. 2002 January 17; 21(3): 475-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821959&dopt=Abstract

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Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett's esophagus. Author(s): Mork H, Scheurlen M, Al-Taie O, Zierer A, Kraus M, Schottker K, Jakob F, Kohrle J. Source: International Journal of Cancer. Journal International Du Cancer. 2003 June 20; 105(3): 300-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704661&dopt=Abstract

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Glutathione S-transferase-pi expression is downregulated in patients with Barrett's esophagus and esophageal adenocarcinoma. Author(s): Brabender J, Lord RV, Wickramasinghe K, Metzger R, Schneider PM, Park JM, Holscher AH, DeMeester TR, Danenberg KD, Danenberg PV. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 May-June; 6(3): 359-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022988&dopt=Abstract

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Guidelines for managing short-segment Barrett's esophagus. Author(s): Spechler SJ. Source: Am J Manag Care. 2000 October; 6(16 Suppl): S891-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184661&dopt=Abstract

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Guidelines of the French Society of Digestive Endoscopy: monitoring of Barrett's esophagus. The Council of the French Society of Digestive Endoscopy. Author(s): Boyer J, Robaszkiewicz M. Source: Endoscopy. 2000 June; 32(6): 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10863922&dopt=Abstract

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Health-related quality of life and severity of symptoms in patients with Barrett's esophagus and gastroesophageal reflux disease patients without Barrett's esophagus. Author(s): Eloubeidi MA, Provenzale D. Source: The American Journal of Gastroenterology. 2000 August; 95(8): 1881-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950030&dopt=Abstract

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Helicobacter pylori colonization of Barrett's esophagus and its progression to cancer. Author(s): Wright TA, Myskow M, Kingsnorth AN. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 1997 July; 10(3): 196-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9280079&dopt=Abstract

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Helicobacter pylori in Barrett's esophagus and in normal or inflamed esophageal mucosa: a retrospective study. Author(s): Sirigu F, Capeccioni S, Dessi A, Masia AM. Source: Riv Eur Sci Med Farmacol. 1994 September-December; 16(5-6): 131-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7480972&dopt=Abstract

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Helicobacter pylori infection and adenocarcinoma arising in Barrett's esophagus. Author(s): Quddus MR, Henley JD, Sulaiman RA, Palumbo TC, Gnepp DR. Source: Human Pathology. 1997 September; 28(9): 1007-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9308723&dopt=Abstract

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Hepatoid adenocarcinoma in Barrett's esophagus associated with achalasia: first case report. Author(s): Tanigawa H, Kida Y, Kuwao S, Uesugi H, Ojima T, Kobayashi N, Saigenji K, Okayasu I. Source: Pathology International. 2002 February; 52(2): 141-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940219&dopt=Abstract

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HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagusassociated adenocarcinoma. Author(s): Walch A, Bink K, Hutzler P, Hofler H, Werner M. Source: Human Pathology. 2000 October; 31(10): 1332-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11070129&dopt=Abstract

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HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagusassociated adenocarcinoma. Author(s): Brien TP, Odze RD, Sheehan CE, McKenna BJ, Ross JS. Source: Human Pathology. 2000 January; 31(1): 35-9. Erratum In: Hum Pathol 2000 April; 31(4): 524. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665910&dopt=Abstract

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Her-2/neu gene amplification, elevated mRNA expression, and protein overexpression in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus. Author(s): Walch A, Specht K, Bink K, Zitzelsberger H, Braselmann H, Bauer M, Aubele M, Stein H, Siewert JR, Hofler H, Werner M. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2001 June; 81(6): 791-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406641&dopt=Abstract

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Hiatal hernia and acid reflux frequency predict presence and length of Barrett's esophagus. Author(s): Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Source: Digestive Diseases and Sciences. 2002 February; 47(2): 256-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855539&dopt=Abstract

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High grade dysplasia/esophageal adenocarcinoma in short segment Barrett's esophagus. Author(s): Iqbal M, Youngberg GA, Young MF, Thomas E. Source: Southern Medical Journal. 1997 August; 90(8): 828-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9258311&dopt=Abstract

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High power setting argon plasma coagulation for the eradication of Barrett's esophagus. Author(s): Pereira-Lima JC, Busnello JV, Saul C, Toneloto EB, Lopes CV, Rynkowski CB, Blaya C. Source: The American Journal of Gastroenterology. 2000 July; 95(7): 1661-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925965&dopt=Abstract

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High-grade dysplasia and superficial adenocarcinoma in Barrett's esophagus: histological mapping and expression of p53, p21 and Bcl-2 oncoproteins. Author(s): Chatelain D, Flejou JF. Source: Virchows Archiv : an International Journal of Pathology. 2003 January; 442(1): 18-24. Epub 2002 September 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536310&dopt=Abstract

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High-grade dysplasia in Barrett's esophagus. The case for esophagectomy. Author(s): Collard JM. Source: Chest Surg Clin N Am. 2002 February; 12(1): 77-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901935&dopt=Abstract

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High-grade dysplasia in Barrett's esophagus: surveillance or operation? Author(s): Pellegrini CA, Pohl D. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2000 March-April; 4(2): 131-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885959&dopt=Abstract

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High-grade dysplasia within Barrett's esophagus: controversies regarding clinical opinions and approaches. Author(s): Al-Kasspooles MF, Hill HC, Nava HR, Smith JL, Douglass HO, Gibbs JF. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2002 April; 9(3): 222-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923127&dopt=Abstract

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Histological and anatomic changes in Barrett's esophagus after antireflux surgery. Author(s): Low DE, Levine DS, Dail DH, Kozarek RA. Source: The American Journal of Gastroenterology. 1999 January; 94(1): 80-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9934735&dopt=Abstract

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Histology of Barrett's esophagus and dysplasia. Author(s): Guindi M, Riddell RH. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 349-68, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916665&dopt=Abstract

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Histopathologic practices for esophageal biopsy specimens: survey results and implications for surveillance in patients with Barrett's esophagus. Author(s): Geisinger KR, Sheppard EA, Teot LA, Raab SS. Source: American Journal of Clinical Pathology. 1998 August; 110(2): 219-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9704621&dopt=Abstract

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How far to go? Screening and surveillance in Barrett's esophagus. Author(s): Lieberman DA, Sampliner RE. Source: Am J Manag Care. 2001 February; 7(1 Suppl): S19-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225349&dopt=Abstract

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Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus. Author(s): Klump B, Hsieh CJ, Holzmann K, Gregor M, Porschen R. Source: Gastroenterology. 1998 December; 115(6): 1381-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9834265&dopt=Abstract

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Iatrogenic esophagobronchial fistula arising in irradiated Barrett's esophagus. Author(s): Anderson TM, Nwogu CE, Loree TR, Cheng CC, Hughes JM, Nava HR. Source: International Journal of Gastrointestinal Cancer. 2001; 30(3): 161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540028&dopt=Abstract

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Immunohistochemical markers for Barrett's esophagus and associations to esophageal Z-line appearance. Author(s): Wallner B, Sylvan A, Janunger KG, Bozoky B, Stenling R. Source: Scandinavian Journal of Gastroenterology. 2001 September; 36(9): 910-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521979&dopt=Abstract

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Immunohistological study of cell cycle-related factors, oncogene expression, and cell proliferation in adenocarcinoma developed in Barrett's esophagus. Author(s): Fujii T, Nakagawa S, Hanzawa M, Sueyoshi S, Fujita H, Shirouzu K, Yamana H. Source: Oncol Rep. 2003 March-April; 10(2): 427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579284&dopt=Abstract

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Impact of antireflux surgery on Barrett's esophagus. Author(s): Gutschow CA, Schroder W, Prenzel K, Bollschweiler E, Romagnoli R, Collard JM, Holscher AH. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2002 July; 387(3-4): 138-45. Epub 2002 July 09. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172858&dopt=Abstract

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Impact of esophageal acid exposure on the endoscopic reversal of Barrett's esophagus. Author(s): Sampliner RE, Camargo L, Fass R. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 270-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866260&dopt=Abstract

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Impact of imprint cytology in detecting short segment Barrett's esophagus. Author(s): Yazgan Y, Demirturk L, Ozel AM, Yildirim S, Ercan M. Source: Journal of Clinical Gastroenterology. 2003 February; 36(2): 126-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544194&dopt=Abstract

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Importance of bile reflux in Barrett's esophagus. Author(s): Richter JE. Source: Digestive Diseases (Basel, Switzerland). 2000-2001; 18(4): 208-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356992&dopt=Abstract

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In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5aminolevulinic acid. Author(s): van Veen RL, Aalders MC, Pasma KL, Siersema PD, Haringsma J, van de Vrie W, Gabeler EE, Robinson DJ, Sterenborg HJ. Source: Lasers in Surgery and Medicine. 2002; 31(5): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430146&dopt=Abstract

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In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus. Author(s): Jackle S, Gladkova N, Feldchtein F, Terentieva A, Brand B, Gelikonov G, Gelikonov V, Sergeev A, Fritscher-Ravens A, Freund J, Seitz U, Schroder S, Soehendra N. Source: Endoscopy. 2000 October; 32(10): 750-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11068833&dopt=Abstract

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Increased acid and bile reflux in Barrett's esophagus compared to reflux esophagitis, and effect of proton pump inhibitor therapy. Author(s): Menges M, Muller M, Zeitz M. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232672&dopt=Abstract

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Increased c-myb mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma. Author(s): Brabender J, Lord RV, Danenberg KD, Metzger R, Schneider PM, Park JM, Salonga D, Groshen S, Tsao-Wei DD, DeMeester TR, Holscher AH, Danenberg PV. Source: The Journal of Surgical Research. 2001 August; 99(2): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469901&dopt=Abstract

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Increased DNA adducts in Barrett's esophagus and reflux-related esophageal malignancies. Author(s): Salminen JT, Ramo OJ, Ahotupa MO, Farkkila MA, Salo JA. Source: Annals of Medicine. 2002; 34(7-8): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553496&dopt=Abstract

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Intestinal metaplasia is the probable common precursor of adenocarcinoma in Barrett's esophagus and adenocarcinoma of the gastrica cardia. Author(s): Conio M, Cameron AJ. Source: Gastrointestinal Endoscopy. 2001 December; 54(6): 799-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762326&dopt=Abstract

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Intraepithelial high-grade neoplasia and early adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment techniques. Author(s): May A, Gossner L, Pech O, Muller H, Vieth M, Stolte M, Ell C. Source: Endoscopy. 2002 August; 34(8): 604-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173079&dopt=Abstract

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Is Barrett's esophagus dangerous? Author(s): Weinstein WM. Source: Endoscopy. 2002 December; 34(12): 1007-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471547&dopt=Abstract

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Is Barrett's esophagus in veterans associated with colonic neoplasia? A retrospective analysis. Author(s): Mukherjee S. Source: The American Journal of Gastroenterology. 2002 May; 97(5): 1274. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014752&dopt=Abstract

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Is duodenogastroesophageal reflux impliated in Barrett's esophagus? Author(s): Lehrer JK, Katz PO. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2463-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358274&dopt=Abstract

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Is there a link between cervical inlet patch and Barrett's esophagus? Author(s): Avidan B, Sonnenberg A, Chejfec G, Schnell TG, Sontag SJ. Source: Gastrointestinal Endoscopy. 2001 June; 53(7): 717-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375577&dopt=Abstract

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Is there publication bias in the reporting of cancer risk in Barrett's esophagus? Author(s): Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS. Source: Gastroenterology. 2000 August; 119(2): 333-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10930368&dopt=Abstract

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Is topical delta-aminolevulinic acid adequate for photodynamic therapy in Barrett's esophagus? A pilot study. Author(s): Ortner MA, Zumbusch K, Liebetruth J, Ebert B, Fleige B, Dietel M, Lochs H. Source: Endoscopy. 2002 August; 34(8): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173080&dopt=Abstract

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Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett's esophagus with high-grade dysplasia. Author(s): Falk GW, Rice TW, Goldblum JR, Richter JE. Source: Gastrointestinal Endoscopy. 1999 February; 49(2): 170-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9925694&dopt=Abstract

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Karyometry in Barrett's esophagus. Author(s): da Silva VD, Prolla JC, Sharma P, Sampliner R, Thompson D, Bartels PH. Source: Anal Quant Cytol Histol. 2001 February; 23(1): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233742&dopt=Abstract

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KTP laser ablation of Barrett's esophagus after anti-reflux surgery results in long-term loss of intestinal metaplasia. Potassium-titanyl-phosphate. Author(s): Bowers SP, Mattar SG, Waring PJ, Galloway K, Nasir A, Pascal R, Hunter JG, Mattear SG. Source: Surgical Endoscopy. 2003 January; 17(1): 49-54. Epub 2002 October 08. Erratum In: Surg Endosc. 2003 Jan; 17(1): 173. Mattear Sg [corrected to Mattar Sg]. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364985&dopt=Abstract

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KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett's esophagus. Author(s): Gossner L, May A, Stolte M, Seitz G, Hahn EG, Ell C. Source: Gastrointestinal Endoscopy. 1999 January; 49(1): 8-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869716&dopt=Abstract

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Lack of impact of therapy on extent of Barrett's esophagus in 67 patients. Author(s): Sampliner RE, Garewal HS, Fennerty MB, Aickin M. Source: Digestive Diseases and Sciences. 1990 January; 35(1): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1967235&dopt=Abstract

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Laparoscopic antireflux surgery: disease-related quality of life assessment before and after surgery in GERD patients with and without Barrett's esophagus. Author(s): Kamolz T, Granderath F, Pointner R. Source: Surgical Endoscopy. 2003 June; 17(6): 880-5. Epub 2003 March 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618934&dopt=Abstract

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Laparoscopic transhiatal esophagectomy for Barrett's esophagus with high grade dysplasia. Author(s): Luketich JD, Nguyen NT, Schauer PR. Source: Jsls. 1998 January-March; 2(1): 75-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9876716&dopt=Abstract

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Length of the esophagus in patients with gastroesophageal reflux disease and Barrett's esophagus compared to controls. Author(s): Korn O, Csendes A, Burdiles P, Braghetto I, Sagastume H, Biagini L. Source: Surgery. 2003 April; 133(4): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717351&dopt=Abstract

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Life expectancy and cancer risk in patients with Barrett's esophagus: a prospective controlled investigation. Author(s): Eckardt VF, Kanzler G, Bernhard G. Source: The American Journal of Medicine. 2001 July; 111(1): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448658&dopt=Abstract

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Lifestyle factors and Barrett's esophagus. Author(s): Caygill CP, Johnston DA, Lopez M, Johnston BJ, Watson A, Reed PI, Hill MJ. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094845&dopt=Abstract

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Limited resection for early adenocarcinoma in Barrett's esophagus. Author(s): Stein HJ, Feith M, Mueller J, Werner M, Siewert JR. Source: Annals of Surgery. 2000 December; 232(6): 733-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11088068&dopt=Abstract

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Local treatment of early cancer in short Barrett's esophagus by means of argon plasma coagulation: initial experience. Author(s): May A, Gossner L, Gunter E, Stolte M, Ell C. Source: Endoscopy. 1999 August; 31(6): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10494693&dopt=Abstract

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Long-term endoscopic surveillance of Barrett's esophagus. Author(s): Sampliner RE. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1912-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499764&dopt=Abstract

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Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study. Author(s): Conio M, Blanchi S, Lapertosa G, Ferraris R, Sablich R, Marchi S, D'Onofrio V, Lacchin T, Iaquinto G, Missale G, Ravelli P, Cestari R, Benedetti G, Macri G, Fiocca R, Munizzi F, Filiberti R. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1931-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499768&dopt=Abstract

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Long-term follow-up and factors predictive of recurrence in Barrett's esophagus treated by argon plasma coagulation and acid suppression. Author(s): Kahaleh M, Van Laethem JL, Nagy N, Cremer M, Deviere J. Source: Endoscopy. 2002 December; 34(12): 950-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471537&dopt=Abstract

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Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia. Author(s): Schnell TG, Sontag SJ, Chejfec G, Aranha G, Metz A, O'Connell S, Seidel UJ, Sonnenberg A. Source: Gastroenterology. 2001 June; 120(7): 1607-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375943&dopt=Abstract

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Long-term outcome of antireflux surgery in patients with Barrett's esophagus. Author(s): Hofstetter WL, Peters JH, DeMeester TR, Hagen JA, DeMeester SR, Crookes PF, Tsai P, Banki F, Bremner CG. Source: Annals of Surgery. 2001 October; 234(4): 532-8; Discussion 538-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573046&dopt=Abstract

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Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus. Author(s): Parrilla P, Martinez de Haro LF, Ortiz A, Munitiz V, Molina J, Bermejo J, Canteras M. Source: Annals of Surgery. 2003 March; 237(3): 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616111&dopt=Abstract

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Long-term results of classic antireflux surgery in 152 patients with Barrett's esophagus: clinical, radiologic, endoscopic, manometric, and acid reflux test analysis before and late after operation. Author(s): Csendes A, Braghetto I, Burdiles P, Puente G, Korn O, Diaz JC, Maluenda F. Source: Surgery. 1998 June; 123(6): 645-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9626315&dopt=Abstract

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Low glutathione and glutathione S-transferase levels in Barrett's esophagus as compared to normal esophageal epithelium. Author(s): van Lieshout EM, Tiemessen DM, Witteman BJ, Jansen JB, Peters WH. Source: Japanese Journal of Cancer Research : Gann. 1999 January; 90(1): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076569&dopt=Abstract

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Magnified view of adenocarcinoma in short segment Barrett's esophagus treated by endoscopic mucosal resection. Author(s): Yagi K, Nakamura A, Sekine A, Tamiya Y, Oyamatsu M. Source: Gastrointestinal Endoscopy. 2002 February; 55(2): 278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818942&dopt=Abstract

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Management of Barrett's esophagus with and without dysplasia. Author(s): Triadafilopoulos G. Source: Scandinavian Journal of Gastroenterology. Supplement. 2003; (237): 40-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797681&dopt=Abstract

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Management of Barrett's esophagus with high-grade dysplasia. Author(s): Pacifico RJ, Deschamps C, Wang KK. Source: The Surgical Clinics of North America. 2002 August; 82(4): 683-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472124&dopt=Abstract

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Management of Barrett's esophagus. Author(s): Younes Z, Duncan MD, Harmon JW. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 November; 14 Suppl D: 35D-43D. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110610&dopt=Abstract

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Medical management of Barrett's esophagus. Author(s): Lee TJ, Kahrilas PJ. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 405-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629098&dopt=Abstract

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Medical treatment of Barrett's esophagus. Author(s): Spechler SJ. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2000 March-April; 4(2): 119-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885955&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588538&dopt=Abstract

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Methylene blue chromoendoscopy for Barrett's esophagus: coming soon to your GI unit? Author(s): Canto MI. Source: Gastrointestinal Endoscopy. 2001 September; 54(3): 403-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522995&dopt=Abstract

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Methylene blue chromoendoscopy for detection of short-segment Barrett's esophagus. Author(s): Sharma P, Topalovski M, Mayo MS, Weston AP. Source: Gastrointestinal Endoscopy. 2001 September; 54(3): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522967&dopt=Abstract

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Methylene blue chromoendoscopy for the detection of Barrett's esophagus in a Greek cohort. Author(s): Kouklakis GS, Kountouras J, Dokas SM, Molyvas EJ, Vourvoulakis GP, Minopoulos GI. Source: Endoscopy. 2003 May; 35(5): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701007&dopt=Abstract

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Methylene blue staining in Barrett's esophagus. Author(s): Ragunath K, Krasner N. Source: Gastrointestinal Endoscopy. 2001 November; 54(5): 673-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11677499&dopt=Abstract

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Methylene blue staining of dysplastic and nondysplastic Barrett's esophagus: an in vivo and ex vivo study. Author(s): Canto MI, Setrakian S, Willis JE, Chak A, Petras RE, Sivak MV. Source: Endoscopy. 2001 May; 33(5): 391-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11396755&dopt=Abstract

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Methylene blue staining: is it really useful in Barrett's esophagus? Author(s): Dave U, Shousha S, Westaby D. Source: Gastrointestinal Endoscopy. 2001 March; 53(3): 333-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231393&dopt=Abstract

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Methylene blue-directed biopsies improve detection of intestinal metaplasia and dysplasia in Barrett's esophagus. Author(s): Canto MI, Setrakian S, Willis J, Chak A, Petras R, Powe NR, Sivak MV Jr. Source: Gastrointestinal Endoscopy. 2000 May; 51(5): 560-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10805842&dopt=Abstract

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Molecular alterations of Barrett's esophagus on microdissected endoscopic biopsies. Author(s): Romagnoli S, Roncalli M, Graziani D, Cassani B, Roz E, Bonavina L, Peracchia A, Bosari S, Coggi G. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2001 February; 81(2): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232646&dopt=Abstract

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Molecular phenotype of spontaneously arising 4N (G2-tetraploid) intermediates of neoplastic progression in Barrett's esophagus. Author(s): Barrett MT, Pritchard D, Palanca-Wessels C, Anderson J, Reid BJ, Rabinovitch PS. Source: Cancer Research. 2003 July 15; 63(14): 4211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874028&dopt=Abstract

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Mucin core peptide expression can help differentiate Barrett's esophagus from intestinal metaplasia of the stomach. Author(s): Glickman JN, Shahsafaei A, Odze RD. Source: The American Journal of Surgical Pathology. 2003 October; 27(10): 1357-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508397&dopt=Abstract

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Mucosal ablation in Barrett's esophagus. Author(s): Walker SJ, Selvasekar CR, Birbeck N. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(1): 22-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060039&dopt=Abstract

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Multilayered epithelium in Barrett's esophagus. Author(s): Takubo K, Honma N, Arai T. Source: The American Journal of Surgical Pathology. 2001 November; 25(11): 1460-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684967&dopt=Abstract

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Mutations in the mitochondrial DNA D-Loop region occur frequently in adenocarcinoma in Barrett's esophagus. Author(s): Miyazono F, Schneider PM, Metzger R, Warnecke-Eberz U, Baldus SE, Dienes HP, Aikou T, Hoelscher AH. Source: Oncogene. 2002 May 23; 21(23): 3780-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032845&dopt=Abstract

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Neoplastic risk assessment in Barrett's esophagus: How far have we come? Author(s): Noffsinger A. Source: Human Pathology. 2003 October; 34(10): 965-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14608528&dopt=Abstract

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New treatments for Barrett's esophagus. Author(s): Sampliner RE. Source: Semin Gastrointest Dis. 1997 April; 8(2): 68-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9109694&dopt=Abstract

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Newly developed Barrett's esophagus after subtotal esophagectomy. Author(s): Franchimont D, Covas A, Brasseur C, Laethem JL, El-Nakadi I, Deviere J. Source: Endoscopy. 2003 October; 35(10): 850-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551864&dopt=Abstract

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Non-goblet cell population of Barrett's esophagus: an immunohistochemical demonstration of intestinal differentiation. Author(s): Chaves P, Cardoso P, de Almeida JC, Pereira AD, Leitao CN, Soares J. Source: Human Pathology. 1999 November; 30(11): 1291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10571507&dopt=Abstract

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Nonsteroidal anti-inflammatory drug use, body mass index, and anthropometry in relation to genetic and flow cytometric abnormalities in Barrett's esophagus. Author(s): Vaughan TL, Kristal AR, Blount PL, Levine DS, Galipeau PC, Prevo LJ, Sanchez CA, Rabinovitch PS, Reid BJ. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 August; 11(8): 745-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163328&dopt=Abstract

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Nonsurgical management of Barrett's esophagus with high-grade dysplasia. Author(s): Pacifico RJ, Wang KK. Source: Surg Oncol Clin N Am. 2002 April; 11(2): 321-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424853&dopt=Abstract

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Normalization of esophageal pH with high-dose proton pump inhibitor therapy does not result in regression of Barrett's esophagus. Author(s): Sharma P, Sampliner RE, Camargo E. Source: The American Journal of Gastroenterology. 1997 April; 92(4): 582-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9128303&dopt=Abstract

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Once or twice daily doses of proton pump inhibitor in treating Barrett's esophagus? Author(s): Savarino V, Mela GS, Zentilin P, Celle G, Vigneri S. Source: The American Journal of Gastroenterology. 1995 May; 90(5): 845-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7733108&dopt=Abstract

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Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett's esophagus. Author(s): Li XD, Boppart SA, Van Dam J, Mashimo H, Mutinga M, Drexler W, Klein M, Pitris C, Krinsky ML, Brezinski ME, Fujimoto JG. Source: Endoscopy. 2000 December; 32(12): 921-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147939&dopt=Abstract

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Ornithine decarboxylase activity in Barrett's esophagus: a potential marker for dysplasia. Author(s): Garewal HS, Sampliner R, Gerner E, Steinbronn K, Alberts D, Kendall D. Source: Gastroenterology. 1988 March; 94(3): 819-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3338650&dopt=Abstract

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Ornithine decarboxylase and polyamine levels in columnar upper gastrointestinal mucosae in patients with Barrett's esophagus. Author(s): Garewal HS, Gerner EW, Sampliner RE, Roe D. Source: Cancer Research. 1988 June 1; 48(11): 3288-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3130189&dopt=Abstract

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Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients. Author(s): Peters JH, Clark GW, Ireland AP, Chandrasoma P, Smyrk TC, DeMeester TR. Source: The Journal of Thoracic and Cardiovascular Surgery. 1994 November; 108(5): 813-21; Discussion 821-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967662&dopt=Abstract

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Outcome of esophageal adenocarcinoma detected during endoscopic biopsy surveillance for Barrett's esophagus. Author(s): Incarbone R, Bonavina L, Saino G, Bona D, Peracchia A. Source: Surgical Endoscopy. 2002 February; 16(2): 263-6. Epub 2001 November 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967675&dopt=Abstract

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Outcomes of dysplasia arising in Barrett's esophagus: a dynamic view. Author(s): Romagnoli R, Collard JM, Gutschow C, Yamusah N, Salizzoni M. Source: Journal of the American College of Surgeons. 2003 September; 197(3): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946790&dopt=Abstract

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p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Author(s): Bian YS, Osterheld MC, Fontolliet C, Bosman FT, Benhattar J. Source: Gastroenterology. 2002 April; 122(4): 1113-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910361&dopt=Abstract

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p53 expression in low grade dysplasia in Barrett's esophagus: correlation with interobserver agreement and disease progression. Author(s): Skacel M, Petras RE, Rybicki LA, Gramlich TL, Richter JE, Falk GW, Goldblum JR. Source: The American Journal of Gastroenterology. 2002 October; 97(10): 2508-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385431&dopt=Abstract

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P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus. Author(s): Schneider PM, Stoeltzing O, Roth JA, Hoelscher AH, Wegerer S, Mizumoto S, Becker K, Dittler HJ, Fink U, Siewert JR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 August; 6(8): 3153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10955797&dopt=Abstract

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P53 protein and malignant progression in Barrett's metaplasia (Barrett's esophagus). Author(s): Younes M, Ertan A, Lechago J. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1200-1; Author Reply 1201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809848&dopt=Abstract

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Pathology of Barrett's esophagus by proton magnetic resonance spectroscopy and a statistical classification strategy. Author(s): Doran ST, Falk GL, Somorjai RL, Lean CL, Himmelreich U, Philips J, Russell P, Dolenko B, Nikulin AE, Mountford CE. Source: American Journal of Surgery. 2003 March; 185(3): 232-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620562&dopt=Abstract

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Persistent genetic abnormalities in Barrett's esophagus after photodynamic therapy. Author(s): Krishnadath KK, Wang KK, Taniguchi K, Sebo TJ, Buttar NS, Anderson MA, Lutzke LS, Liu W. Source: Gastroenterology. 2000 September; 119(3): 624-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982754&dopt=Abstract

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Phenotype of Barrett's esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction: an immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45 MI. Author(s): Glickman JN, Wang H, Das KM, Goyal RK, Spechler SJ, Antonioli D, Odze RD. Source: The American Journal of Surgical Pathology. 2001 January; 25(1): 87-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145256&dopt=Abstract

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Photodynamic therapy for Barrett's esophagus and high grade dysplasia: results of a patient satisfaction survey. Author(s): Hemminger LL, Wolfsen HC. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2002 July-August; 25(4): 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195146&dopt=Abstract

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Photodynamic therapy for Barrett's esophagus with dysplasia and/or early stage carcinoma: long-term results. Author(s): Overholt BF, Panjehpour M, Halberg DL. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872083&dopt=Abstract

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Photodynamic therapy for Barrett's esophagus: a review. Author(s): Kelty CJ, Marcus SL, Ackroyd R. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(2): 137-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220421&dopt=Abstract

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Photodynamic therapy for mucosal esophageal adenocarcinoma and dysplastic Barrett's esophagus. Author(s): Wolfsen HC. Source: Digestive Diseases (Basel, Switzerland). 2002; 20(1): 5-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145415&dopt=Abstract

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Photodynamic therapy in Barrett's esophagus. Author(s): Wang KK, Kim JY. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 483-9, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629104&dopt=Abstract

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Possibilities of chromoesophagoscopy for diagnosis of Barrett's esophagus. Author(s): Khadjibaev AM, Nizamkhodjaev ZM, Kholmatov RM, Mirzakhmedov BM, Mirzaev BB. Source: World Journal of Surgery. 2003 March; 27(3): 315-8. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607058&dopt=Abstract

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Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systematic review. Author(s): Dulai GS, Guha S, Kahn KL, Gornbein J, Weinstein WM. Source: Gastroenterology. 2002 January; 122(1): 26-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781277&dopt=Abstract

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Prevalence of Barrett's esophagus by endoscopy and histologic studies: a prospective evaluation of 306 control subjects and 376 patients with symptoms of gastroesophageal reflux. Author(s): Csendes A, Smok G, Burdiles P, Quesada F, Huertas C, Rojas J, Korn O. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005324&dopt=Abstract

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Prevalence of Barrett's esophagus in an urban Korean population: a multicenter study. Author(s): Lee JI, Park H, Jung HY, Rhee PL, Song CW, Choi MG. Source: Journal of Gastroenterology. 2003; 38(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560918&dopt=Abstract

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Prevalence of Barrett's esophagus in asymptomatic individuals. Author(s): Gerson LB, Shetler K, Triadafilopoulos G. Source: Gastroenterology. 2002 August; 123(2): 461-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145799&dopt=Abstract

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Progression or regression of Barrett's esophagus--is it all in the eye of the beholder? Author(s): Dekel R, Wakelin DE, Wendel C, Green C, Sampliner RE, Garewal HS, Martinez P, Fass R. Source: The American Journal of Gastroenterology. 2003 December; 98(12): 2612-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14687805&dopt=Abstract

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Prospective evaluation of multilayered epithelium in Barrett's esophagus. Author(s): Shields HM, Rosenberg SJ, Zwas FR, Ransil BJ, Lembo AJ, Odze R. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3268-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11774935&dopt=Abstract

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Quality of life in patients with Barrett's esophagus undergoing surveillance. Author(s): Fisher D, Jeffreys A, Bosworth H, Wang J, Lipscomb J, Provenzale D. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358232&dopt=Abstract

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Quantification of duodenogastric reflux in Barrett's esophagus. Author(s): Liron R, Parrilla P, Martinez de Haro LF, Ortiz A, Robles R, Lujan JA, Fuente T, Andres B. Source: The American Journal of Gastroenterology. 1997 January; 92(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8995933&dopt=Abstract

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Quantitative endoscopy: precise computerized measurement of metaplastic epithelial surface area in Barrett's esophagus. Author(s): Kim R, Baggott BB, Rose S, Shar AO, Mallory DL, Lasky SS, Kressloff M, Faccenda LY, Reynolds JC. Source: Gastroenterology. 1995 February; 108(2): 360-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7835577&dopt=Abstract

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Re: Gross et al.--Ablation therapy for Barrett's esophagus. Author(s): Hershfield NB. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2932-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425582&dopt=Abstract

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Reasons for current practices in managing Barrett's esophagus. Author(s): Lin OS, Mannava S, Hwang KL, Triadafilopoulos G. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060041&dopt=Abstract

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Recent developments in Barrett's esophagus. Author(s): Garewal HS. Source: Current Oncology Reports. 2000 May; 2(3): 271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122853&dopt=Abstract

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Reflux disease and Barrett's esophagus. Author(s): Haag S, Holtmann G. Source: Endoscopy. 2003 February; 35(2): 112-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561004&dopt=Abstract

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Reflux disease and Barrett's esophagus. Author(s): Rosch T. Source: Endoscopy. 2002 November; 34(11): 851-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430068&dopt=Abstract

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Results of photodynamic therapy for ablation of dysplasia and early cancer in Barrett's esophagus and effect of oral steroids on stricture formation. Author(s): Panjehpour M, Overholt BF, Haydek JM, Lee SG. Source: The American Journal of Gastroenterology. 2000 September; 95(9): 2177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007214&dopt=Abstract

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Risk factors for dysplasia in patients with Barrett's esophagus (BE): results from a multicenter consortium. Author(s): Gopal DV, Lieberman DA, Magaret N, Fennerty MB, Sampliner RE, Garewal HS, Falk GW, Faigel DO. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1537-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924649&dopt=Abstract

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Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus. Author(s): Kaur BS, Khamnehei N, Iravani M, Namburu SS, Lin O, Triadafilopoulos G. Source: Gastroenterology. 2002 July; 123(1): 60-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105834&dopt=Abstract

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Role of acid and bile in the genesis of Barrett's esophagus. Author(s): Kauer WK, Stein HJ. Source: Chest Surg Clin N Am. 2002 February; 12(1): 39-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901931&dopt=Abstract

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Role of molecular biology in the follow-up of patients who have Barrett's esophagus. Author(s): Casson AG. Source: Chest Surg Clin N Am. 2002 February; 12(1): 93-111, Ix-X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901936&dopt=Abstract

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Screening for Barrett's esophagus in colonoscopy patients with and without heartburn. Author(s): Rex DK, Cummings OW, Shaw M, Cumings MD, Wong RK, Vasudeva RS, Dunne D, Rahmani EY, Helper DJ. Source: Gastroenterology. 2003 December; 125(6): 1670-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14724819&dopt=Abstract

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Screening for Barrett's esophagus. Author(s): Spechler SJ. Source: Reviews in Gastroenterological Disorders. 2002; 2 Suppl 2: S25-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478241&dopt=Abstract

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Screening for Barrett's esophagus: searching for a new technique. Author(s): Qureshi WA, El-Zimaity H, Green LK, Graham DY. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1565-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094891&dopt=Abstract

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Serum selenium levels in relation to markers of neoplastic progression among persons with Barrett's esophagus. Author(s): Rudolph RE, Vaughan TL, Kristal AR, Blount PL, Levine DS, Galipeau PC, Prevo LJ, Sanchez CA, Rabinovitch PS, Reid BJ. Source: Journal of the National Cancer Institute. 2003 May 21; 95(10): 750-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759393&dopt=Abstract

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Short-segment Barrett's esophagus associated with high-grade dysplasia. Author(s): Morita K, Fujimori T, Ono Y, Masuyama H, Nakamura T, Terano A. Source: Journal of Gastroenterology. 2002; 37(12): 1083-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522544&dopt=Abstract

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Significance of acid exposure in Barrett's esophagus. Author(s): Fitzgerald RC. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650815&dopt=Abstract

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Standard antireflux operations in patients who have Barrett's esophagus. Current results. Author(s): Parrilla P, Martinez de Haro LF, Ortiz A, Munitiz V. Source: Chest Surg Clin N Am. 2002 February; 12(1): 113-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901924&dopt=Abstract

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Surgical therapies in Barrett's esophagus. Author(s): Lundell L. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 433-47, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629100&dopt=Abstract

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Surgical therapy for Barrett's esophagus: prevention, protection and excision. Author(s): DeMeester TR. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2002; 15(2): 109-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220416&dopt=Abstract

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Surveillance and surgery for Barrett's esophagus: more results from Sweden. Author(s): Lord RV, Gurski RR. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2136-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190192&dopt=Abstract

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Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett's esophagus. Author(s): Pfefer TJ, Paithankar DY, Poneros JM, Schomacker KT, Nishioka NS. Source: Lasers in Surgery and Medicine. 2003; 32(1): 10-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516065&dopt=Abstract

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The approach to high grade dysplasia in Barrett's esophagus. Author(s): Case CL, Barkin JS. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094886&dopt=Abstract

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The association of short segment Barrett's esophagus with intestinal metaplasia in stomach. Author(s): Tuncer I, Ugras S, Uygan I, Turkdogan K, Kosem M. Source: Turk J Gastroenterol. 2003 March; 14(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14593535&dopt=Abstract

•

The economic burden of Barrett's esophagus in a Medicaid population. Author(s): Amonkar MM, Kalsekar ID, Boyer JG. Source: The Annals of Pharmacotherapy. 2002 April; 36(4): 605-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918506&dopt=Abstract

•

The economic impact of the diagnosis of dysplasia in Barrett's esophagus. Author(s): Ofman JJ, Lewin K, Ramers C, Ippoliti A, Lieberman D, Weinstein W. Source: The American Journal of Gastroenterology. 2000 October; 95(10): 2946-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051373&dopt=Abstract

•

The management of dysplastic Barrett's esophagus: where do we go from here? Author(s): Peters JH. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2002 April; 9(3): 215-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923124&dopt=Abstract

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The pathogenesis of Barrett's esophagus. Author(s): Fitzgerald RC, Farthing MJ. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 233-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916657&dopt=Abstract

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The pathogenesis of Barrett's esophagus: a process in continuum or discontinuum. Author(s): Fitzgerald RC, Farthing MJ. Source: Current Gastroenterology Reports. 2000 December; 2(6): 421-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11079041&dopt=Abstract

•

The role of endoscopic ultrasound in the diagnosis and management of Barrett's esophagus. Author(s): Owens MM, Kimmey MB. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 325-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916663&dopt=Abstract

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TP53 mutations in malignant and premalignant Barrett's esophagus. Author(s): Dolan K, Walker SJ, Gosney J, Field JK, Sutton R. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2003; 16(2): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823203&dopt=Abstract

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Ultrasound-guided fine-needle aspiration diagnosis of adenocarcinoma of esophagus with signet-ring cell features arising in Barrett's esophagus: a case report. Author(s): Baloch Z, Lyle S, Hoda RS, Gupta PK. Source: Diagnostic Cytopathology. 1998 July 1; 19(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664184&dopt=Abstract

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Unresolved issues in Barrett's esophagus in the new millennium. Author(s): Falk G. Source: Digestive Diseases (Basel, Switzerland). 2000; 18(1): 27-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10729735&dopt=Abstract

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Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Author(s): Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 1888-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190150&dopt=Abstract

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Upregulation of ornithine decarboxylase mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma. Author(s): Brabender J, Lord RV, Danenberg KD, Metzger R, Schneider PM, Uetake H, Kawakami K, Park JM, Salonga D, Peters JH, DeMeester TR, Holscher AH, Danenberg PV. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2001 March-April; 5(2): 174-81; Discussion 182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331481&dopt=Abstract

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•

Use of a novel monoclonal antibody in diagnosis of Barrett's esophagus. Author(s): Griffel LH, Amenta PS, Das KM. Source: Digestive Diseases and Sciences. 2000 January; 45(1): 40-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695612&dopt=Abstract

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Use of a simple symptom questionnaire to predict Barrett's esophagus in patients with symptoms of gastroesophageal reflux. Author(s): Gerson LB, Edson R, Lavori PW, Triadafilopoulos G. Source: The American Journal of Gastroenterology. 2001 July; 96(7): 2005-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11467625&dopt=Abstract

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Use of lasers in Barrett's esophagus. Author(s): Weston AP. Source: Gastrointest Endosc Clin N Am. 2003 July; 13(3): 467-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629103&dopt=Abstract

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Usefulness of cytopathology and histology in the evaluation of Barrett's esophagus in a community hospital. Author(s): Alexander JA, Jones SM, Smith CJ, Doull JA, Gietzen TH, Rathgaber SW. Source: Gastrointestinal Endoscopy. 1997 October; 46(4): 318-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9351033&dopt=Abstract

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Utilization of cytokeratins 7 and 20 does not differentiate between Barrett's esophagus and gastric cardiac intestinal metaplasia. Author(s): Mohammed IA, Streutker CJ, Riddell RH. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2002 June; 15(6): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065774&dopt=Abstract

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Validity of the specialized columnar epithelium as a diagnostic criterion of the short segment Barrett's esophagus. Author(s): Bak YT, Jung GM, Yeon JE, Kim JS, Byun KS, Kim JH, Kim JG, Lee CH, Kim HK, Won NH. Source: Korean J Intern Med. 1998 July; 13(2): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9735664&dopt=Abstract

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Videoendoscopy with vital double dye staining (crystal violet and methylene blue) for detection of a minute focus of early stage adenocarcinoma in Barrett's esophagus: a case report. Author(s): Tabuchi M, Sueoka N, Fujimori T. Source: Gastrointestinal Endoscopy. 2001 September; 54(3): 385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522988&dopt=Abstract

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Virtual biopsies in Barrett's esophagus using an impedance probe. Author(s): Gonzalez-Correa CA, Brown BH, Smallwood RH, Kalia N, Stoddard CJ, Stephenson TJ, Haggie SJ, Slater DN, Bardhan KD. Source: Annals of the New York Academy of Sciences. 1999 April 20; 873: 313-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372179&dopt=Abstract

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Vital staining and Barrett's esophagus. Author(s): Canto MI. Source: Gastrointestinal Endoscopy. 1999 March; 49(3 Pt 2): S12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10049441&dopt=Abstract

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Waist-to-hip ratio, weight gain, and dietary and serum selenium are associated with DNA content flow cytometry in Barrett's esophagus. Author(s): Moe GL, Kristal AR, Levine DS, Vaughan TL, Reid BJ. Source: Nutrition and Cancer. 2000; 36(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798210&dopt=Abstract

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What is the optimal medical therapy for Barrett's esophagus? Author(s): DeVault KR. Source: Digestive Diseases (Basel, Switzerland). 2000-2001; 18(4): 217-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356993&dopt=Abstract

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What you need to know about Barrett's esophagus. Author(s): Rockey AD. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2002 November-December; 25(6): 237-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488685&dopt=Abstract

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CHAPTER 2. NUTRITION AND BARRETT’S ESOPHAGUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Barrett’s esophagus.

Finding Nutrition Studies on Barrett’s Esophagus 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 “Barrett’s esophagus” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

Barrett's esophagus in children. Diagnosis and management. Author(s): Department of Surgery, Medical University of South Carolina, Charleston. Source: Othersen, H B Ocampo, R J Parker, E F Smith, C D Tagge, E P Ann-Surg. 1993 June; 217(6): 676-80; discussion 680-1 0003-4932

•

Barrett's esophagus: a model premalignant lesion for adenocarcinoma. Author(s): Department of Medicine, Tucson Veterans Administration Medical Center, Arizona 85723. Source: Garewal, H S Sampliner, R Prev-Med. 1989 September; 18(5): 749-56 0091-7435

•

Chemoprevention of Barrett's esophagus and oral leukoplakia. Author(s): University of Arizona Cancer Center, Tucson. Source: Garewal, H S Adv-Exp-Med-Biol. 1992; 320129-36 0065-2598

•

Chemopreventive studies in Barrett's esophagus: a model premalignant lesion for esophageal adenocarcinoma. Author(s): Department of Medicine, Tucson Veterans Affairs Medical Center, Ariz. 85723. Source: Garewal, H S Sampliner, R E Fennerty, M B J-Natl-Cancer-Inst-Monogr. 1992; (13): 51-4 1052-6773

•

Cytology of small-cell carcinoma arising in Barrett's esophagus. Author(s): Department of Pathology, Saint Agnes Medical Center, Fresno, California 93720, USA. Source: Chen, K T Diagn-Cytopathol. 2000 September; 23(3): 180-2 8755-1039

•

Effect of gastroduodenal juice and dietary fat on the development of Barrett's esophagus and esophageal neoplasia: an experimental rat model. Author(s): Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033-4612. Source: Clark, G W Smyrk, T C Mirvish, S S Anselmino, M Yamashita, Y Hinder, R A DeMeester, T R Birt, D F Ann-Surg-Oncol. 1994 May; 1(3): 252-61 1068-9265

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Esophageal ulceration associated with 13-cis-retinoic acid therapy in patients with Barrett's esophagus. Author(s): Section of Gastroenterology and Hematology-Oncology, Tucson Veterans Administration Medical Center, Arizona 85723. Source: Fennerty, B Sampliner, R Garewal, H Gastrointest-Endosc. 1989 Sep-October; 35(5): 442-3 0016-5107

•

Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett's esophagus. Author(s): First Department of Medicine, University of Pecs, Hungary, H-7643 Pecs, Ifjusag u. 13., Hungary. [email protected] Source: Kiraly, A Suto, G Czimmer, J Horvath, O P Mozsik, G J-Physiol-Paris. 2001 JanDecember; 95(1-6): 197-200 0928-4257

•

Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett's esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants. Author(s): College of Pharmacy, Seoul National University, Seoul, South Korea. Source: Lee, J S Oh, T Y Ahn, B O Cho, H Kim, W B Kim, Y B Surh, Y J Kim, H J Hahm, K B Mutat-Res. 2001 September 1; 480-481: 189-200 0027-5107

Nutrition

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Lack of impact of therapy on extent of Barrett's esophagus in 67 patients. Author(s): Section of Gastroenterology, University of Arizona Health Sciences Center, Tucson. Source: Sampliner, R E Garewal, H S Fennerty, M B Aickin, M Dig-Dis-Sci. 1990 January; 35(1): 93-6 0163-2116

•

Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus. Author(s): Gastroenterology Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA. Source: Kaur, Baljeet S Khamnehei, Niloufar Iravani, Mohamed Namburu, Sai S Lin, Otto Triadafilopoulos, George Gastroenterology. 2002 July; 123(1): 60-7 0016-5085

•

Waist-to-hip ratio, weight gain, and dietary and serum selenium are associated with DNA content flow cytometry in Barrett's esophagus. Author(s): Department of Family and Consumer Sciences, Seattle Pacific University, WA 98119, USA. Source: Moe, G L Kristal, A R Levine, D S Vaughan, T L Reid, B J Nutr-Cancer. 2000; 36(1): 7-13 0163-5581

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

•

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

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

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

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

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

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

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

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

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

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

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

•

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND BARRETT’S ESOPHAGUS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Barrett’s esophagus. 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 Barrett’s esophagus 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 “Barrett’s esophagus” (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 Barrett’s esophagus: •

A structural chiropractic approach to the management of diffuse idiopathic skeletal hyperostosis. Author(s): Troyanovich SJ, Buettner M. Source: Journal of Manipulative and Physiological Therapeutics. 2003 March-April; 26(3): 202-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704313&dopt=Abstract

•

Cytology of small-cell carcinoma arising in Barrett's esophagus. Author(s): Chen KT. Source: Diagnostic Cytopathology. 2000 September; 23(3): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945905&dopt=Abstract

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•

Dietary antioxidants and DNA damage in patients on long-term acid-suppression therapy: a randomized controlled study. Author(s): White KL, Chalmers DM, Martin IG, Everett SM, Neville PM, Naylor G, Sutcliffe AE, Dixon MF, Turner PC, Schorah CJ. Source: The British Journal of Nutrition. 2002 September; 88(3): 265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207836&dopt=Abstract

•

Experiences of a parent support group with the long-term consequences of esophageal atresia. Author(s): Schier F, Korn S, Michel E. Source: Journal of Pediatric Surgery. 2001 April; 36(4): 605-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11283887&dopt=Abstract

•

Long-term survival of a patient with widespread metastases from Barrett's adenocarcinoma. Author(s): Mason GR, Micetich K, Aranha GV. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2001 August; 27(5): 509-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504525&dopt=Abstract

•

Malignant progression in Barrett's esophagus: pathology and molecular biology. Author(s): Mueller J, Werner M, Siewert JR. Source: Recent Results Cancer Res. 2000; 155: 29-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10693236&dopt=Abstract

•

Molecular biology of esophageal cancer. Author(s): D'Amico TA, Harpole DH Jr. Source: Chest Surg Clin N Am. 2000 August; 10(3): 451-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10967750&dopt=Abstract

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Risk factors for Barrett's oesophagus: a life history approach to behavioural assessment in the distant past. Author(s): Ritenbaugh C, Sampliner R, Aickin M, Garewal H, Meyskens F. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 1995 December; 4(6): 459-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8580781&dopt=Abstract

•

Strategies for molecular intervention in esophageal cancers and their precursor lesions. Author(s): Schrump DS, Nguyen DM.

Alternative Medicine 91

Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 1999; 12(3): 181-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631909&dopt=Abstract

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

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

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•

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

•

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

•

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

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

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CHAPTER 4. DISSERTATIONS ON BARRETT’S ESOPHAGUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to Barrett’s esophagus. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “Barrett’s esophagus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Barrett’s esophagus, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Barrett’s Esophagus ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to Barrett’s esophagus. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Telomere Length and Chromosomal Instability in the Neoplastic Progression of Barrett's Esophagus by Finley, Jennifer Christine, PhD from University of Washington, 2003, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3102651

•

The Effects of Antireflux Surgery on Esophageal Function, Cellular Proliferation and Apoptosis for Barrett's Esophagus by Chen, Long-Qi, PhD from Universite De Montreal (Canada), 2003, 182 pages http://wwwlib.umi.com/dissertations/fullcit/NQ82721

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

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CHAPTER 5. ESOPHAGUS

CLINICAL

TRIALS

AND

BARRETT’S

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Barrett’s esophagus.

Recent Trials on Barrett’s Esophagus The following is a list of recent trials dedicated to Barrett’s esophagus.8 Further information on a trial is available at the Web site indicated. •

Familial Aggregation of Barrett's Esophagus Condition(s): Barrett's Esophagus; Esophageal Neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This research study is trying to determine whether Barrett's esophagus and associated esophageal cancers, specifically esophageal adenocarcinoma are inherited in certain families. Persons who are affected with Barrett's esophagus or esophageal cancer (adenocarcinoma type) are asked to complete a questionnaire that determines their habits and asks a detailed family history. Family members of patients seen at University Hospitals of Cleveland are also being recruited for screening tests of their esophagus. The investigators plan to eventually screen family members at all participating institutions. This research will eventually lead to the identification of inherited genetic changes that cause Barrett's esophagus and esophageal cancer. It will help the investigators develop better methods for preventing or identifying esophageal cancer at an early curable stage. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058877

8

These are listed at www.ClinicalTrials.gov.

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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Barrett’s esophagus” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON BARRETT’S ESOPHAGUS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Barrett’s esophagus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Barrett’s esophagus, we have not necessarily excluded non-medical patents in this bibliography.

Patent Applications on Barrett’s Esophagus As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Barrett’s esophagus:

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 10 This has been a common practice outside the United States prior to December 2000.

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•


Arrangement for the treatment of barrett's esophagus Inventor(s): Boll, James H.; (Jamaica Plain, MA), Cho, George; (Hopkinton, MA) Correspondence: Donald N. Halgren; 35 Central Street; Manchester; MA; 01944; US Patent Application Number: 20030191363 Date filed: April 8, 2002 Abstract: A method for the treatment of Barrett's Esophagus of a patient having endothelial esophageal complications. The treatment comprises connecting a wavelength specific light source to an elongated light guide having a distal end, the light guide arranged within a lumen of a steerable endoscope, guiding the endoscope into the esophagus of the patient, energyzing the light source, and manipulating the distal end of the light source onto a target on the endothelial complications inside of the patient's esophagus for the selective thermolysis of the target in the esophagus, thereby reverting the red secretory esophageal lining to a normal lining. Excerpt(s): The present invention relates to the apparatus and the method of using that apparatus for the treatment of Barrett's Esophagus, and more particularly the utilization of a light apparatus to accomplish that treatment. A condition known as Barrett's Esophagus, develops in some people who have chronic gastroesophageal reflux disease (GERD) or otherwise known as inflammation of the esophagus (esophagitis). The esophagus is a muscular, membranous tube, about 25 cm long, through which food passes from the pharynx at the rear of the mouth, into the stomach. 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 Barrett’s esophagus, 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 “Barrett’s esophagus” (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 Barrett’s esophagus. You can also use this procedure to view pending patent applications concerning Barrett’s esophagus. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON BARRETT’S ESOPHAGUS Overview This chapter provides bibliographic book references relating to Barrett’s esophagus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Barrett’s esophagus 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 “Barrett’s esophagus” (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 Barrett’s esophagus: •

Diseases of the Gastroesophageal Mucosa: The Acid-Related Disorders Source: Totowa, NJ: The Humana Press, Inc. 2001. 199 p. 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: Gastric acid-related diseases are among the most commonly encountered disorders in clinical practice. The last decade has witnessed profound changes in the clinical approach to this family of conditions, which includes gastroesophageal reflux disease (GERD), peptic ulcers of all etiologies (causes), and dyspepsia (heartburn). This text emphasizes the diagnosis and treatment of these conditions, with subtext on epidemiology and pathophysiology (where their understanding is important for management conditions). Eleven chapters cover the management of peptic ulcer disease;

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the epidemiology, demographics and pathophysiology of Helicobacter pylori-related diseases, including gastritis, ulcers, and cancer; the diagnosis and treatment of Helicobacter-pylori related diseases; the management of nonsteroidal antiinflammatory drug (NSAID) related ulcers; nonvariceal upper gastrointestinal bleeding; ZollingerEllison syndrome and other acid-hypersecretory states; dyspepsia and nonulcer dyspepsia; the epidemiology and pathophysiology of gastroesophageal reflux disease (GERD); the diagnosis and treatment of GERD; Barrett's esophagus and adenocarcinoma; and extraesophageal manifestations of GERD. Each chapter includes a list of references and a subject index concludes the text.

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

Barrett's Esophagus by H.W. Tilanus (Editor), et al; ISBN: 1402001029; http://www.amazon.com/exec/obidos/ASIN/1402001029/icongroupinterna

•

Barrett's Esophagus and Esophageal Adenocarcinoma by Prateek Sharma (Editor), et al; ISBN: 0632045094; http://www.amazon.com/exec/obidos/ASIN/0632045094/icongroupinterna

•

Barrett's Esophagus: Pathophysiology, Diagnosis and Management by Stuart Jon Spechler (Editor); ISBN: 0444009493; http://www.amazon.com/exec/obidos/ASIN/0444009493/icongroupinterna

•

The Official Patient's Sourcebook on Barrett's Esophagus: A Revised and Updated Directory for the Internet Age by Icon Health Publications; ISBN: 0597832749; http://www.amazon.com/exec/obidos/ASIN/0597832749/icongroupinterna

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

Books

•

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Gastroesophageal Reflux Disease Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 16-65. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: Gastroesophageal reflux occurs physiologically in all persons, when gastric (stomach) contents reflux (go back up) into the esophagus. However, due to acid neutralization by saliva and prompt esophageal clearance of the refluxed material, symptoms occur in only a minority of people. This chapter on gastroesophageal reflux disease (GERD) is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The authors of this chapter note that with inconsistency of definitions and methods of diagnosis, it is difficult to determine the current prevalence of GERD in the general population. The incidence of GERD is estimated to be 4.5 per 100,000, with a dramatic increase in persons over the age of 40. Complications of GERD include bleeding (less than 2 percent), ulceration (around 5 percent), and strictures (from 1.2 to 20 percent). Barrett's esophagus has been identified in 10 to 20 percent of GERD patients. The typical symptoms of GERD include heartburn, acid regurgitation, and dysphagia (swallowing difficulties). The authors consider the role of different diagnostic tests including symptom description, manometry and lower esophageal pressure measurement, radiology, scintigraphy, upper gastrointestinal endoscopy, Bernstein test (which measures esophageal acid sensitivity), 24 hour ambulatory pH monitoring, and acid suppression (as a diagnostic test). The goals of therapy are to provide adequate symptom relief in all patients and to prevent complications. Treatment options include antacids and lifestyle modifications, acid suppression therapy, H2 receptor antagonists, prokinetic drugs (i.e., cisapride and sucralfate), and treatment of GERD complications, including esophageal peptic stricture (narrowing). Maintenance therapy is required in most patients with GERD. The authors also discuss the treatment of endoscopy negative reflux disease, the use of surgery to treat GERD, the effect of GERD on quality of life, and Barrett's esophagus. 6 figures. 8 tables. 324 references.

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CHAPTER 8. PERIODICALS AND NEWS ON BARRETT’S ESOPHAGUS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Barrett’s esophagus.

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

Dusa announces new study of Levulan PDT for Barrett's esophagus Source: Reuters Industry Breifing Date: April 06, 2001

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•

Colonization with cagA-positive H. pylori may prevent Barrett's esophagus Source: Reuters Medical News Date: October 09, 2000

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Several factors predict risk of progression of Barrett's esophagus to cancer Source: Reuters Medical News Date: July 28, 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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Regression of Barrett's esophagus seen with elimination of acid reflux Source: Reuters Medical News Date: September 29, 1999

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Adenocarcinoma less common than expected in Barrett's esophagus Source: Reuters Medical News Date: August 23, 1999

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Barrett's esophagus treatment costs dominated by medications Source: Reuters Medical News Date: August 18, 1999

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Cardiac intestinal metaplasia different from Barrett's esophagus Source: Reuters Medical News Date: March 19, 1999

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Argon beam plasma coagulation restores squamous lining in Barrett's esophagus Source: Reuters Medical News Date: November 16, 1998

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Barrett's esophagus linked to congenital varicella-zoster infection Source: Reuters Medical News Date: August 17, 1998

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FDA approves Axcan's photofrin for Barrett's esophagus Source: Reuters Industry Breifing Date: August 04, 2003

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Oxidative stress plays a role in malignant transformation of Barrett's esophagus Source: Reuters Medical News Date: January 03, 2003

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Coagulation method can eradicate Barrett's esophagus, but recurrence is common Source: Reuters Industry Breifing Date: December 26, 2002

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Findings shed light on cell changes after surgery for Barrett's esophagus Source: Reuters Industry Breifing Date: December 25, 2002

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Axcan files Photofrin with FDA for Barrett's Esophagus dysplasia Source: Reuters Industry Breifing Date: May 30, 2002

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Axcan files Barrett's esophagus dysplasia drug for EU approval Source: Reuters Industry Breifing Date: April 11, 2002

Periodicals and News

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Screening boosts survival in Barrett's esophagus Source: Reuters Health eLine Date: April 01, 2002

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Cancer surveillance may improve survival for patients with Barrett's esophagus Source: Reuters Medical News Date: March 29, 2002

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COX-2 inhibitors may be useful treatment for Barrett's esophagus Source: Reuters Industry Breifing Date: March 20, 2002

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Peers influences adoption of new treatment for Barrett's esophagus Source: Reuters Industry Breifing Date: March 11, 2002

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GERD symptoms and hiatal hernia are risk factors for Barrett's esophagus Source: Reuters Medical News Date: January 29, 2002

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Controversy surrounds treatment of high-grade dysplasia in Barrett's esophagus Source: Reuters Medical News Date: July 23, 2001

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Barrett's Esophagus-Related Adenocarcinoma: Better Estimates Are Needed Source: Reuters Medical News Date: March 06, 1997

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Characteristics Of Reflux Disease Predict Barrett's Esophagus Source: Reuters Medical News Date: January 20, 1997

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Phototherapy An Effective Approach To Management Of Barrett's Esophagus Source: Reuters Medical News Date: October 24, 1996

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Successful Reversal of Barrett's Esophagus Reported Source: Reuters Medical News Date: March 28, 1996

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Barrett's Esophagus Not A Risk Factor For Colorectal Cancer Source: Reuters Medical News Date: November 28, 1995

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Barrett's Esophagus Highlighted at ACG Meeting Source: Reuters Medical News Date: October 16, 1995

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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.

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

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

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At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Barrett’s esophagus. 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).

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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 Barrett’s esophagus 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 “Barrett’s esophagus” (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 approval.” If the orphan product about which you are seeking information is approved for

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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 Barrett’s esophagus: •

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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APPENDICES

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

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

•

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

•

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

•

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

•

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

•

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

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

•

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

11

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

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•

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

•

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

•

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

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

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

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

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

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

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

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

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

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

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

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Barrett’s esophagus” (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 3103 21 623 2 2 3751

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “Barrett’s esophagus” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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

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

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

19 Adapted 20

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Barrett’s esophagus can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 Barrett’s esophagus. 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 Barrett’s esophagus. 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 “Barrett’s esophagus”:

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Within the health topic page dedicated to Barrett’s esophagus, 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 Upper Endoscopy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/upperendoscopy/index.htm Upper GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/uppergi/index.htm What Is Upper GI Endoscopy? Source: American Gastroenterological Association http://www.gastro.org/clinicalRes/brochures/uppergi.html

•

Treatment FDA Approves Photofrin for Treatment of Pre-Cancerous Lesions in Barretts Esophagus Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01246.html

•

Specific Conditions/Aspects Achalasia and Esophageal Motility Disorders Source: Society of Thoracic Surgeons http://www.sts.org/doc/4120 Barrett's Esophagus Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/barretts/index.htm

•

Children Esophageal Atresia and Tracheoesophageal Fistula Source: American Academy of Family Physicians http://familydoctor.org/345.xml

•

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

Patient Resources

•

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Prevention/Screening Cost-Effectiveness of Screening and Surveillance for Barrett Esophagus Source: American College of Physicians http://www.annals.org/cgi/content/full/138/3/I-41

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 Barrett’s esophagus. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Barrett Esophagus Source: Danbury, CT: National Organization for Rare Disorders, Inc. 2001. 5 p. Contact: Available from National Organization for Rare Disorders (NORD). P.O. Box 1968, Danbury, CT 06813-1968. (800) 999-6673 or (203) 744-0100. Fax (203) 798-2291. TDD (203) 797-9590. E-mail: [email protected]. Website: www.rarediseases.org. PRICE: $7.50. Summary: Barrett syndrome is a rare disorder caused by chronic inflammation and ulceration of the esophagus. Symptoms develop due to reflux of stomach acid into the esophagus and may include heartburn and recurring pain behind the sternum. Late symptoms may include a narrowing of the esophagus and difficulty swallowing. This fact sheet describes the symptoms, causes, affected population, and standard and investigational therapies. Disorders with similar symptoms, including achalasia, gastroesophageal reflux, and hiatal hernia are briefly discussed. The fact sheet lists 3 resources for more information. 14 references. The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Barrett’s esophagus. 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

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


•

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

•

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

•

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

•

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

•

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

•

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

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

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Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Barrett’s esophagus”. 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 “Barrett’s esophagus” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Barrett’s esophagus” (or a synonym) into the search box, and click “Submit Query.”

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

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

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

22

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

23

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Barrett’s Esophagus Barrett's esophagus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001143.htm GERD Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000265.htm Peptic ulcer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000206.htm

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Signs & Symptoms for Barrett’s Esophagus Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Difficulty swallowing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm

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Dysphagia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Melena Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003130.htm •

Diagnostics and Tests for Barrett’s Esophagus Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Endoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003338.htm Gastric acid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003883.htm

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Nutrition for Barrett’s Esophagus Caffeine 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

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Background Topics for Barrett’s Esophagus Asymptomatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002217.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

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

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

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

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BARRETT’S ESOPHAGUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] 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

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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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] 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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH]

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Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [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] 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] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes

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associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]

Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] 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] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the

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digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Reflux: Reflux of bile mainly into the upper digestive tract, but also into the pancreas. [NIH]

Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] 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] 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

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walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

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] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [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] Cardiology: The study of the heart, its physiology, and its functions. [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-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] Causal: Pertaining to a cause; directed against a cause. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH]

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Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] 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] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and

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photocoagulation. [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] Colonoscope: A thin, lighted tube used to examine the inside of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [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] Colposcope: A lighted magnifying instrument used for examination of the vagina and cervix. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements,

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megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Criterion: A standard by which something may be judged. [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] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH]

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Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or

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tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [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] Difluoromethylornithine: DFMO. An anticancer drug that has been shown to reduce the risk of cancer in animals. [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] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] 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] Dosimeter: In nuclear science and radiotherapy, a device used for the detection and measurement of radiation absorbed dose or any dose-related ionizing radiation received by the individual; a radiation meter intended to measure absorbed dose. [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] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenogastric Reflux: Reflux of duodenal contents into the stomach. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU]

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Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [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] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [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] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [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] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or

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biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] 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] 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] 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 Stricture: A narrowing of the esophagus often caused by acid flowing back from the stomach. This condition may require surgery. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excisional biopsy: A surgical procedure in which an entire lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH]

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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] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including

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cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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 Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] 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] Gastroscopy: Endoscopic examination, therapy, or surgery of the interior of the stomach. [NIH]

Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory

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techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] 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] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [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] 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] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] 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] Hairy cell leukemia: A type of chronic leukemia in which the abnormal white blood cells appear to be covered with tiny hairs when viewed under a microscope. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal

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condition of gametes in diploids. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematoxylin: A dye obtained from the heartwood of logwood (Haematoxylon campechianum Linn., Leguminosae) used as a stain in microscopy and in the manufacture of ink. [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] 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] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

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] Histology: The study of tissues and cells under a microscope. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform

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quality throughout. [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] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hyperostosis: Increase in the mass of bone per unit volume. [NIH] Hypertonic Solutions: Solutions that have a greater osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Image Cytometry: A technique encompassing morphometry, densitometry, neural networks, and expert systems that has numerous clinical and research applications and is particularly useful in anatomic pathology for the study of malignant lesions. The most common current application of image cytometry is for DNA analysis, followed by quantitation of immunohistochemical staining. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of

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neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [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] Intracellular: Inside a cell. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH]

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Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invertebrates: Animals that have no spinal column. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] 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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH]

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Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [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] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lumen: The cavity or channel within a tube or tubular organ. [EU] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] 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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic

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moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [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] Manometry: Tests that measure muscle pressure and movements in the GI tract. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] 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] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH]

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Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU]

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Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] 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 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]

Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopathy: Any disease of a muscle. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH]

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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] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neutralization: An act or process of neutralizing. [EU] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye

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and the medical and surgical treatment of its defects and diseases. [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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [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]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease.

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[NIH]

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

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions

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between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photofrin: A drug used in photodynamic therapy that is absorbed by tumor cells; when absorbed by cancer cells and exposed to light, it becomes active and kills the cancer cells. [NIH]

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] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [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 that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together

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can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [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] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Porfimer sodium: An anticancer drug that is also used in cancer prevention. It belongs to the family of drugs called photosensitizing agents. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH]

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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] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prokinetic Drugs: Medicines that cause muscles in the GI tract to move food. An example is cisapride (SIS-uh-pryd) (Propulsid). [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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] Publication Bias: The influence of study results on the chances of publication and the tendency of investigators, reviewers, and editors to submit or accept manuscripts for

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publication based on the direction or strength of the study findings. Publication bias has an impact on the interpretation of clinical trials and meta-analyses. Bias can be minimized by insistence by editors on high-quality research, thorough literature reviews, acknowledgement of conflicts of interest, modification of peer review practices, etc. [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]

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]

Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] 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] 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] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and

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causes a specific physiologic effect in the cell. [NIH] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] 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] Research Support: Financial support of research activities. [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] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

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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] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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

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brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [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] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] 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] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

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Sternum: Breast bone. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Systemic: Affecting the entire body. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH]

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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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermal ablation: A procedure using heat to remove tissue or a part of the body, or destroy its function. For example, to remove the lining of the uterus, a catheter is inserted through the cervix into the uterus, a balloon at the end of the catheter is inflated, and fluid inside the balloon is heated to destroy the lining of the uterus. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [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] 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] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH]

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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] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be 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] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH]

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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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vagotomy: The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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

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nearest millimeter. [NIH] Weight Gain: Increase in body weight over existing weight. [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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [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] 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] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH]

177

INDEX A Abdominal, 18, 137, 147, 162, 173 Abdominal fat, 18, 137 Abdominal Pain, 137, 173 Aberrant, 55, 137 Ablate, 30, 32, 33, 137, 148 Ablation, 9, 17, 20, 31, 32, 34, 42, 52, 66, 71, 77, 78, 137, 172 Acceptor, 137, 157, 162, 172 Acetylcholine, 137, 161 Adaptability, 137, 142, 143 Adaptation, 26, 137 Adenoma, 35, 137 Adipose Tissue, 137 Adjustment, 137 Adverse Effect, 137, 169 Aerobic, 8, 137, 159 Affinity, 137, 158, 170 Algorithms, 5, 20, 35, 138, 141 Alimentary, 47, 52, 59, 62, 69, 81, 138, 163 Alkaloid, 138, 142 Alleles, 138, 156, 157 Alpha-helix, 138, 156 Alternative medicine, 89, 91, 108, 138, 144 Aluminum, 138, 171 Amino Acid Sequence, 138, 139 Amino Acids, 138, 158, 163, 165, 166, 168, 169, 173 Aminolevulinic Acid, 16, 49, 53, 64, 66, 138 Amplification, 24, 61, 138, 151 Ampulla, 138, 148 Anaerobic, 8, 138 Anal, 18, 22, 66, 138, 149, 160 Analog, 138, 150 Analogous, 22, 138, 147, 173 Anastomosis, 6, 138 Aneuploidy, 13, 18, 20, 31, 39, 139 Angiogenesis, 29, 30, 139 Animal model, 6, 16, 26, 30, 139, 173 Anomalies, 139, 160 Anthropometry, 72, 139 Antibacterial, 139, 170 Antibiotic, 139, 170 Antibodies, 8, 139, 154, 164 Antibody, 19, 82, 138, 139, 144, 154, 155, 159, 167, 170 Antigen, 138, 139, 144, 155

Anti-inflammatory, 9, 18, 72, 139, 140, 142, 162 Anti-Inflammatory Agents, 139, 140, 142 Antioxidant, 139, 162 Anus, 138, 139, 141 Apoptosis, 12, 26, 34, 35, 36, 42, 43, 93, 139 Aqueous, 140, 146 Arachidonic Acid, 140, 166 Arginase, 26, 140 Arginine, 26, 140, 161, 162, 167, 173 Argon, 9, 43, 52, 61, 67, 68, 106, 140 Aromatic, 140, 158 Arterial, 140, 166 Arteries, 140, 141, 145, 159, 160 Aspiration, 81, 140, 150, 160 Aspirin, 9, 140 Assay, 9, 19, 35, 140 Asymptomatic, 21, 76, 136, 140 B Bacteria, 8, 139, 140, 141, 149, 151, 157, 159, 164, 170, 173, 174 Bacterial Physiology, 137, 140 Bacteriophage, 140, 173, 174 Base, 13, 38, 140, 146, 156, 171, 172 Benign, 137, 140, 151, 161, 167 Bilateral, 15, 140 Bile, 6, 9, 18, 19, 41, 45, 64, 78, 140, 141, 150, 151, 154, 157, 171 Bile Acids, 6, 140, 151 Bile Acids and Salts, 140 Bile Reflux, 9, 18, 41, 64, 141 Biochemical, 138, 141, 150 Bioluminescence, 141, 157 Biomarkers, 11, 14, 25, 46, 58, 72, 141 Biopsy, 5, 6, 8, 13, 22, 25, 27, 29, 31, 32, 38, 62, 66, 73, 136, 141, 149, 150, 160 Biopsy specimen, 29, 62, 141 Biosynthesis, 140, 141, 162, 169 Biotechnology, 39, 40, 108, 119, 141 Bivalent, 141, 158 Bladder, 14, 35, 141, 166, 174 Bloating, 141, 161 Blood Glucose, 141, 153 Blood pressure, 141, 159, 170 Blood vessel, 139, 141, 148, 164, 171, 172, 174 Blot, 35, 141 Body Fluids, 141, 148, 170, 173

178


Body Mass Index, 72, 141, 162 Bowel, 138, 141, 147, 155, 173 Bowel Movement, 141, 147 Bradykinin, 141, 161 Branch, 54, 133, 142, 146, 163, 170, 172 C Calcium, 142, 144, 148, 169 Capsaicin, 54, 86, 142 Carcinogenesis, 10, 12, 14, 26, 35, 43, 54, 142, 143 Carcinogenic, 12, 142, 155, 166 Carcinogens, 142, 160, 161 Carcinoma, 16, 26, 31, 32, 35, 40, 41, 42, 46, 47, 75, 86, 89, 142 Cardia, 47, 65, 142 Cardiac, 48, 55, 82, 106, 142, 148, 151, 160 Cardiology, 22, 142 Case report, 4, 46, 47, 57, 60, 81, 82, 142 Case-Control Studies, 19, 142, 149 Causal, 26, 142, 149 Celecoxib, 9, 142 Cell Cycle, 63, 142, 146 Cell Death, 139, 142, 160 Cell Differentiation, 142, 169 Cell Division, 12, 140, 142, 143, 146, 159, 164 Cell Lineage, 20, 142 Cell proliferation, 20, 35, 36, 42, 63, 78, 87, 143, 169 Cell Respiration, 143, 159, 168 Cell Size, 143, 150 Cell Survival, 27, 143 Cervical, 65, 143 Cervix, 30, 34, 143, 144, 172 Chemoprevention, 28, 30, 39, 45, 50, 86, 143 Chemopreventive, 14, 36, 86, 143 Chiropractic, 89, 143 Cholesterol, 140, 143 Chromatin, 139, 143 Chromosomal, 10, 12, 13, 23, 93, 138, 139, 143, 164, 171 Chromosome, 13, 139, 143, 151, 152, 156, 157, 159, 171, 173 Chronic, 4, 8, 16, 17, 18, 100, 125, 143, 147, 149, 152, 155, 157, 171, 173 Chronic leukemia, 143, 152 CIS, 17, 86, 143 Clinical Medicine, 9, 143, 165 Clinical trial, 4, 5, 17, 34, 95, 96, 119, 143, 145, 160, 166, 167 Cloning, 141, 143

Coagulation, 9, 33, 43, 52, 61, 67, 68, 106, 142, 143 Cofactor, 144, 166 Cohort Studies, 144, 149 Colitis, 16, 23, 144, 173 Colonoscope, 16, 144 Colonoscopy, 15, 78, 144 Colorectal, 15, 16, 22, 33, 107, 144 Colorectal Cancer, 15, 22, 33, 107, 144 Colposcope, 30, 144 Complement, 144 Complementary and alternative medicine, 89, 91, 144 Complementary medicine, 89, 144 Complete response, 32, 145 Computational Biology, 119, 145 Conduction, 14, 145 Connective Tissue, 35, 145, 157 Connective Tissue Cells, 145 Continuum, 81, 145 Contraindications, ii, 145 Control group, 5, 145 Controlled study, 90, 145 Cornea, 145, 175 Coronary, 22, 145, 159, 160 Coronary Thrombosis, 145, 159, 160 Corpus, 49, 145 Corticosteroids, 9, 145 Cranial, 145, 174 Criterion, 82, 145 Cross-Sectional Studies, 145, 149 Crowding, 16, 35, 145 Cultured cells, 29, 146 Curative, 65, 146, 172 Cutaneous, 15, 146 Cyanide, 146, 159 Cyanosis, 146, 149 Cyclic, 146, 152, 161, 165 Cyclin, 9, 36, 146 Cytogenetics, 14, 146 Cytomegalovirus, 146, 151 Cytomegalovirus Infections, 146, 151 Cytoplasm, 139, 146, 152, 158, 168 Cytotoxic, 142, 146, 167, 169 D Data Collection, 14, 146 Databases, Bibliographic, 119, 146 Decarboxylation, 146, 162, 167 Degenerative, 146, 153 Deletion, 12, 24, 26, 139, 146, 157 Density, 8, 30, 38, 141, 146, 150, 161, 170 Depolarization, 146, 169

Index 179

Diabetes Mellitus, 146, 153 Diagnostic Imaging, 29, 146 Diagnostic procedure, 99, 108, 147 Diaphragm, 147, 153 Difluoromethylornithine, 58, 147 Digestion, 48, 138, 140, 141, 147, 155, 157, 163, 171 Digestive system, 96, 147, 151, 160 Digestive tract, 141, 147, 170 Digoxigenin, 35, 147 Dilatation, 147, 166, 174 Diploid, 139, 147, 159, 164, 165, 173 Direct, iii, 25, 26, 31, 36, 143, 147, 168 Disease Progression, 12, 24, 74, 147 Distal, 25, 26, 75, 100, 147, 148, 151, 156, 166 Dosimeter, 17, 147 Dosimetry, 20, 32, 64, 147 Drug Design, 27, 112, 113, 147 Drug Interactions, 112, 147 Duodenogastric Reflux, 77, 147 Duodenum, 20, 140, 147, 148, 151, 162, 171 Dyspepsia, 101, 147, 161 Dysphagia, 103, 136, 147 Dyspnea, 148, 149 E Efficacy, 16, 17, 32, 34, 52, 147, 148 Electrocoagulation, 52, 143, 148 Electrode, 33, 148 Electrolytes, 140, 148 Electrons, 139, 140, 148, 156, 158, 162, 167 Elementary Particles, 148, 158, 166 Embryo, 142, 148 Enamel, 148, 156 Endemic, 148, 170 Endocrine Glands, 148 Endometrial, 30, 148 Endometrium, 30, 148 Endoscope, 6, 15, 21, 30, 34, 38, 100, 148 Endothelium, 148, 161 Endothelium-derived, 148, 161 Enteropeptidase, 148, 173 Environmental Exposure, 9, 14, 148, 161 Environmental Health, 118, 120, 149 Enzyme, 26, 140, 147, 148, 149, 152, 163, 169, 172, 174 Epidemic, 17, 149, 170 Epidemiologic Studies, 15, 149 Epidemiological, 21, 33, 149 Epidermis, 149, 156 Epithelial, 7, 9, 26, 34, 35, 49, 77, 137, 149, 152, 153

Epithelial Cells, 49, 149, 153 Esophageal Atresia, 90, 124, 149, 172 Esophageal Stricture, 32, 57, 149 Esophagectomy, 30, 32, 62, 67, 72, 149 Esophagitis, 23, 26, 27, 36, 48, 64, 86, 100, 149, 151, 171 Estrogen, 33, 149 Estrogen receptor, 33, 149 Ethnic Groups, 15, 149 Eukaryotic Cells, 149, 155 Excisional, 30, 149 Excisional biopsy, 30, 149 Excitation, 15, 35, 150 Expert Systems, 150, 154 Extracellular, 145, 150, 170 Extracellular Matrix, 145, 150 F Family Planning, 119, 150 Fat, 9, 18, 19, 86, 136, 137, 140, 141, 150, 157, 162 Fatty acids, 150, 166 Fetus, 150, 174 Fine-needle aspiration, 81, 150, 160 Fistula, 63, 124, 149, 150, 151, 172 Flow Cytometry, 83, 87, 150 Fluorescence, 6, 15, 16, 27, 29, 32, 35, 49, 53, 56, 80, 150 Fluorescent Dyes, 150 Fold, 19, 22, 26, 30, 150 Fractionation, 17, 150 G Gallbladder, 137, 147, 150, 151 Gamma Rays, 150, 160, 167 Ganciclovir, 39, 150 Ganglion, 151, 175 Gas, 140, 151, 154, 160, 161, 174 Gastrectomy, 47, 151 Gastric, 6, 8, 14, 37, 39, 57, 59, 82, 101, 103, 136, 151, 153, 163 Gastric Juices, 151, 163 Gastric Mucosa, 59, 151, 163 Gastritis, 49, 102, 151, 171 Gastroduodenal, 26, 86, 151 Gastroesophageal Reflux Disease, 3, 4, 5, 8, 19, 21, 23, 30, 37, 55, 60, 67, 70, 100, 101, 103, 151 Gastrointestinal tract, 5, 6, 15, 20, 32, 103, 151, 173 Gastroscopy, 15, 151 Gels, 11, 151 Gene Amplification, 61, 151

180


Gene Expression, 10, 11, 21, 24, 26, 27, 28, 39, 43, 59, 152 Genetic Markers, 10, 14, 152 Genetic testing, 10, 152 Genetics, 6, 7, 14, 24, 146, 152 Genotype, 14, 152, 164 Gland, 152, 157, 162, 166, 169, 171 Glucose, 141, 146, 152, 153 Glutathione Peroxidase, 152, 169 Glycine, 138, 140, 152, 169 Goblet Cells, 38, 152 Governing Board, 152, 165 Grading, 16, 31, 38, 152 Graft, 152, 154 Granulocytes, 152, 169, 175 Growth, 12, 26, 139, 140, 142, 143, 152, 158, 160, 161, 162, 164, 174 Guanylate Cyclase, 152, 161 H Hairy cell leukemia, 15, 152 Haploid, 152, 164, 165 Health Services, iv, 4, 23, 120, 153 Heartburn, 5, 37, 78, 101, 103, 125, 136, 153 Hematoxylin, 31, 153 Heme, 138, 153, 160, 165 Hemochromatosis, 19, 153 Hemoglobin, 35, 146, 153, 165 Hemoglobin A, 153, 165 Hemorrhage, 148, 153, 171 Hepatic, 11, 153 Hepatitis, 33, 153 Hepatocytes, 153 Hepatology, 33, 103, 153 Hereditary, 15, 153, 163 Heredity, 151, 152, 153 Hernia, 40, 61, 106, 107, 125, 153 Heterogeneity, 23, 138, 153 Hiatal Hernia, 40, 106, 107, 125, 153 Histology, 31, 46, 62, 82, 153, 162 Homogeneous, 21, 145, 153 Hormonal, 15, 154 Hormone, 145, 154, 158, 169 Host, 8, 9, 18, 37, 50, 140, 154, 174 Humoral, 8, 154 Humour, 154 Hybrid, 154 Hybridization, 13, 24, 28, 35, 154, 155, 161 Hydrogen, 137, 140, 152, 154, 157, 159, 161, 162, 166 Hydrolysis, 140, 147, 154, 164, 165, 166, 173 Hyperostosis, 89, 154

Hypertonic Solutions, 43, 154 I Id, 88, 91, 124, 126, 132, 134, 154 Idiopathic, 89, 154 Ileum, 154, 174 Image Cytometry, 32, 154 Immune response, 8, 139, 154, 174 Immune system, 154, 174, 175 Immunoglobulin, 139, 154, 159 Immunohistochemistry, 27, 28, 35, 39, 154 Impairment, 154, 158 In situ, 28, 29, 35, 49, 64, 154 In Situ Hybridization, 28, 35, 155 In vitro, 24, 36, 54, 155, 172 In vivo, 5, 9, 17, 24, 28, 29, 30, 35, 36, 64, 70, 155 Incision, 155, 156 Incompetence, 151, 155 Indicative, 102, 155, 163, 174 Infarction, 22, 145, 155, 159, 160 Infection, 17, 19, 27, 34, 37, 40, 60, 106, 146, 155, 157, 171, 175 Infiltration, 155, 175 Inflammation, 8, 100, 125, 139, 140, 144, 149, 151, 153, 155, 171, 173 Initiation, 12, 28, 155, 172 Inlay, 155, 168 Inorganic, 155, 157, 160 Insecticides, 155, 163 Insight, 12, 155 Intermittent, 155, 157 Internal Medicine, 3, 11, 36, 55, 151, 155 Interstitial, 154, 155 Intestinal, 8, 10, 25, 27, 28, 38, 39, 40, 47, 51, 53, 54, 65, 66, 71, 72, 75, 80, 82, 106, 148, 155 Intestine, 140, 141, 144, 147, 154, 155, 156, 168, 170, 173 Intracellular, 155, 158, 161, 169 Intraepithelial, 47, 53, 65, 155 Intrinsic, 9, 26, 35, 138, 156 Invasive, 22, 30, 32, 34, 42, 156, 157 Invertebrates, 156, 157 Ionizing, 147, 149, 156, 167 Ions, 140, 148, 154, 156 K Kb, 118, 156 Keratin, 39, 156 Kidney Cortex, 156, 158 L Large Intestine, 144, 147, 155, 156, 168, 170 Laser therapy, 5, 156

Index 181

Latent, 156, 165 Lesion, 12, 17, 19, 24, 26, 28, 86, 156, 157, 173 Lethal, 9, 11, 17, 18, 25, 146, 156, 160 Leukemia, 15, 143, 152, 156 Leukocytes, 152, 156, 163 Leukoplakia, 30, 86, 156 Library Services, 132, 156 Life Expectancy, 51, 156 Ligament, 156, 166 Linkage, 15, 22, 23, 152, 156 Linkage Disequilibrium, 15, 156 Lipid, 157, 162 Lipid Peroxidation, 157, 162 Liver, 12, 33, 41, 103, 137, 140, 146, 147, 150, 151, 153, 157, 158, 173 Liver cancer, 33, 157 Localization, 28, 154, 157 Localized, 15, 32, 155, 157, 164, 173 Long-Term Care, 21, 157 Loop, 71, 153, 157 Loss of Heterozygosity, 21, 157 Lower Esophageal Sphincter, 151, 157 Lumen, 27, 100, 149, 157 Luminescence, 5, 157 Lymph, 143, 148, 154, 157 Lymph node, 143, 157 Lymphatic, 148, 155, 157, 170 Lymphoid, 15, 139, 145, 157 Lysine, 157, 173 Lytic, 157, 174 M Magnetic Resonance Imaging, 157, 158 Magnetic Resonance Spectroscopy, 74, 157 Malignancy, 8, 9, 12, 16, 19, 26, 32, 53, 56, 158 Malignant tumor, 6, 158 Manometry, 103, 124, 158 Mediate, 9, 13, 36, 158 Medical Records, 158, 168 MEDLINE, 119, 158 Medulloblastoma, 29, 158 Melanocytes, 158 Melanoma, 15, 158 Membrane, 27, 144, 146, 149, 150, 158, 160, 162, 164, 165, 166, 169, 173 Membrane Proteins, 158, 166 Menopause, 158, 165 Mental Disorders, 97, 158 Mercury, 150, 158 Meta-Analysis, 50, 158

Metallothionein, 43, 158 Methylene Blue, 40, 51, 82, 159 MI, 47, 51, 70, 71, 75, 83, 136, 159 Microbe, 159, 172 Microbiology, 137, 159 Microscopy, 27, 46, 153, 159 Midaxillary line, 159, 174 Millimeter, 159, 175 Mitochondria, 35, 159 Mitochondrial Swelling, 159, 160 Mitosis, 139, 159 Mitotic, 10, 12, 159 Modeling, 12, 15, 21, 22, 147, 159 Modification, 159, 167 Molecular, 6, 11, 14, 19, 21, 24, 26, 27, 28, 31, 33, 36, 39, 71, 78, 90, 119, 121, 138, 141, 145, 146, 147, 158, 159 Molecule, 139, 140, 144, 146, 148, 150, 151, 154, 159, 161, 162, 164, 167, 169, 172 Monitor, 20, 29, 34, 159, 161 Monoclonal, 82, 159, 167 Monosomy, 139, 159 Morphology, 28, 29, 34, 46, 159 Motility, 54, 86, 124, 159 Mucins, 152, 160, 169 Mucosa, 5, 6, 7, 8, 20, 26, 30, 36, 38, 48, 59, 60, 101, 151, 160, 171 Mucositis, 160, 172 Mucus, 27, 54, 160, 173 Multicenter Studies, 21, 160 Multicenter study, 76, 160 Multivariate Analysis, 31, 160 Mustard Gas, 160 Mutagen, 15, 160 Myocardial infarction, 22, 145, 159, 160 Myocardium, 159, 160 Myoglobin, 160, 165 Myopathy, 55, 160 N Nausea, 160, 161 NCI, 1, 15, 96, 117, 143, 160 Necrosis, 34, 139, 155, 159, 160 Need, 3, 6, 10, 32, 33, 34, 51, 83, 101, 102, 112, 113, 127, 137, 160 Needle biopsy, 150, 160 Neoplasia, 8, 9, 22, 24, 47, 53, 65, 86, 160, 161 Neoplasm, 21, 95, 161 Neoplastic, 9, 12, 13, 18, 20, 24, 29, 36, 50, 63, 71, 72, 74, 79, 93, 157, 161 Nerve, 143, 151, 161, 165, 171, 174, 175 Networks, 24, 43, 154, 161

182


Neural, 24, 43, 154, 161 Neutralization, 103, 161 Nitric Oxide, 11, 26, 161 Nitrogen, 138, 140, 161 Nonulcer Dyspepsia, 102, 161 Nuclear, 35, 38, 49, 147, 148, 149, 150, 151, 160, 161 Nuclei, 16, 38, 148, 157, 158, 159, 161, 166 Nucleic acid, 154, 155, 161, 170 Nucleic Acid Hybridization, 154, 161 Nucleus, 139, 143, 146, 148, 149, 150, 161, 166 O Ointments, 161, 162 Oncogene, 59, 63, 71, 161 Oncology, 29, 45, 58, 62, 72, 77, 80, 86, 90, 161 Opacity, 146, 161 Ophthalmology, 22, 161 Organ Culture, 162, 172 Ornithine, 73, 81, 162, 167 Ornithine Decarboxylase, 81, 162 Osmotic, 154, 159, 162 Otolaryngology, 38, 162 Overexpress, 35, 162 Overweight, 10, 18, 87, 162 Oxidation, 137, 139, 152, 157, 162 Oxidative Stress, 86, 162 P P53 gene, 31, 162 Palliative, 162, 172 Pancreas, 137, 141, 147, 151, 153, 162, 173 Pancreatic, 14, 151, 162 Pancreatic cancer, 14, 162 Pancreatic Juice, 151, 162 Paraffin, 27, 162 Patch, 57, 65, 156, 162 Pathogenesis, 7, 19, 27, 28, 39, 80, 81, 162 Pathologic, 8, 47, 139, 141, 145, 163 Pathologic Processes, 139, 163 Pathophysiology, 17, 101, 102, 163 Patient Education, 125, 130, 132, 136, 163 Patient Satisfaction, 75, 163 Peer Review, 85, 163, 167 Pelvic, 163, 166 Pepsin, 163 Pepsin A, 163 Peptic, 36, 101, 103, 135, 163, 171 Peptic Ulcer, 101, 163 Peptide, 71, 148, 156, 163, 165, 166 Peroxidase, 59, 152, 157, 163, 169 Peroxide, 152, 157, 163

Pesticides, 15, 155, 163 Petroleum, 162, 163 Pharmacokinetics, 147, 163 Pharmacologic, 163, 172 Pharynx, 100, 151, 163 Phenotype, 14, 39, 71, 75, 163 Phospholipases, 164, 169 Phospholipids, 150, 164 Photocoagulation, 144, 164 Photodynamic therapy, 16, 32, 42, 48, 64, 66, 74, 75, 78, 164 Photofrin, 106, 113, 124, 164 Photosensitizer, 16, 20, 164 Photosensitizing Agents, 164, 165 Physiologic, 141, 147, 164, 168 Physiology, 41, 54, 137, 140, 142, 151, 164 Pigment, 158, 160, 164 Pilot study, 15, 23, 66, 164 Plants, 138, 152, 159, 164, 172 Plasma, 9, 43, 52, 61, 67, 68, 106, 139, 153, 154, 164, 169 Plasma cells, 139, 164 Plasmid, 151, 164 Platelet Activation, 164, 169 Platelet Aggregation, 161, 164 Platelets, 161, 164, 165 Pleated, 156, 165 Ploidy, 9, 31, 165 Poisoning, 158, 159, 160, 165 Polypeptide, 138, 154, 160, 163, 165 Polyposis, 144, 165 Population Control, 27, 165 Porfimer sodium, 32, 165 Porphyrins, 35, 165 Posterior, 138, 159, 162, 165 Postsynaptic, 165, 169 Potentiation, 165, 169 Practice Guidelines, 120, 165 Precancerous, 15, 34, 49, 143, 165 Preclinical, 34, 165 Precursor, 8, 9, 12, 13, 19, 23, 24, 25, 32, 33, 65, 90, 140, 165, 170 Predisposition, 27, 165 Premalignant, 5, 19, 23, 24, 26, 30, 33, 35, 81, 86, 165 Premenopausal, 15, 165 Prevalence, 8, 10, 18, 21, 23, 24, 27, 31, 33, 36, 37, 43, 44, 50, 76, 103, 166 Primitive neuroectodermal tumors, 158, 166 Probe, 5, 15, 30, 32, 38, 43, 83, 166 Progressive, 12, 13, 142, 152, 160, 164, 166

Index 183

Prokinetic Drugs, 103, 166 Promoter, 13, 21, 33, 39, 63, 74, 166 Proportional, 18, 151, 166 Prospective study, 68, 166 Prostaglandins, 26, 140, 166 Prostate, 14, 141, 166, 173 Protein S, 8, 141, 166, 168 Proteins, 11, 35, 138, 139, 141, 143, 144, 154, 156, 158, 159, 161, 163, 164, 166, 169, 172 Protocol, 5, 6, 22, 32, 66, 166 Proton Pump, 64, 72, 73, 166 Protons, 154, 156, 158, 166, 167 Proximal, 26, 57, 147, 156, 166 Public Policy, 119, 166 Publication Bias, 65, 166 Publishing, 39, 103, 167 Pulse, 159, 167 Putrescine, 162, 167, 170 Pyridoxal, 162, 167 Q Quality of Life, 18, 23, 60, 66, 103, 167 R Race, 18, 167 Radiation, 147, 148, 149, 150, 156, 164, 167, 175 Radiation therapy, 150, 167 Radioactive, 154, 161, 167 Radiology, 103, 167 Radiotherapy, 147, 167 Randomized, 9, 17, 68, 90, 148, 167 Randomized clinical trial, 17, 167 Reactivation, 13, 167 Receptor, 7, 35, 103, 137, 139, 149, 167, 169 Recombination, 152, 168 Rectum, 139, 141, 144, 147, 151, 156, 166, 168 Recurrence, 68, 106, 143, 168 Refer, 1, 144, 157, 168 Refraction, 168, 170 Refractory, 148, 168 Regeneration, 36, 168 Regimen, 148, 168 Regurgitation, 103, 151, 153, 168 Remission, 168 Research Support, 33, 168 Resected, 5, 30, 38, 74, 168 Resection, 32, 45, 53, 67, 69, 168 Respiration, 143, 159, 168 Restoration, 5, 35, 167, 168 Retinoid, 17, 35, 168 Retrospective, 60, 65, 168

Retrospective study, 60, 168 Ribosome, 168, 173 Risk factor, 11, 15, 16, 18, 19, 23, 27, 36, 38, 78, 90, 107, 149, 166, 168 Risk patient, 14, 168 Rodenticides, 163, 168 S Saliva, 103, 169 Salivary, 146, 147, 162, 169 Salivary glands, 146, 147, 169 Salivation, 149, 169 Scleroproteins, 156, 169 Screening, 3, 4, 5, 17, 21, 22, 25, 30, 37, 53, 63, 78, 79, 95, 107, 125, 143, 169 Secretion, 154, 160, 169 Secretory, 100, 169 Selenium, 9, 18, 79, 83, 87, 169 Semen, 166, 169 Sequencing, 31, 169 Serine, 169, 173 Serum, 8, 9, 11, 18, 19, 79, 83, 87, 144, 169 Side effect, 17, 111, 113, 137, 169, 172 Signal Transduction, 36, 169 Skeletal, 89, 169 Skeleton, 169 Skull, 169, 172 Small intestine, 147, 154, 155, 170, 173 Social Environment, 167, 170 Sodium, 32, 148, 165, 170 Solid tumor, 139, 170 Somatic, 154, 159, 170, 171 Sound wave, 145, 170 Specialist, 126, 170 Species, 8, 142, 154, 159, 167, 170, 171, 174, 175 Specificity, 31, 138, 170 Spectrometer, 38, 170 Spectrum, 15, 170 Sperm, 143, 170 Spermidine, 162, 170 Sporadic, 14, 170 Squamous, 7, 20, 25, 26, 28, 30, 34, 36, 38, 106, 170 Squamous Epithelium, 7, 20, 25, 26, 28, 30, 36, 38, 170 Stabilization, 27, 30, 170 Staging, 32, 170 Sternum, 125, 171 Steroids, 78, 145, 171 Stimulus, 148, 150, 171 Stress, 18, 26, 86, 106, 160, 162, 165, 171 Stricture, 32, 57, 78, 103, 149, 171

184


Stroke, 97, 118, 171 Subacute, 155, 171 Subclinical, 155, 171 Subcutaneous, 171, 174 Subspecies, 170, 171 Sucralfate, 103, 171 Supplementation, 6, 171 Support group, 90, 171 Suppression, 41, 50, 51, 68, 90, 103, 171 Symphysis, 166, 171 Symptomatic, 21, 23, 171 Synaptic, 169, 171 Systemic, 50, 141, 155, 167, 171 T Telomerase, 11, 13, 54, 171 Telomere, 13, 93, 171 Temporal, 12, 29, 172 Therapeutics, 89, 112, 172 Thermal, 9, 172 Thermal ablation, 9, 172 Thorax, 137, 172 Thrombosis, 145, 159, 160, 166, 171, 172 Thymidine, 39, 172 Thymidine Kinase, 39, 172 Tissue Culture, 20, 172 Tomography, 22, 25, 29, 30, 49, 50, 64, 73, 158, 172 Tooth Preparation, 137, 172 Topical, 66, 162, 172 Toxic, iv, 146, 149, 163, 167, 169, 172 Toxicity, 16, 147, 158, 171, 172 Toxicology, 120, 172 Toxins, 139, 155, 172 Trachea, 163, 172 Tracheoesophageal Fistula, 124, 149, 172 Transcriptase, 171, 172 Transcription Factors, 36, 172 Transduction, 36, 169, 173 Transfection, 141, 173 Transgenes, 39, 173 Translation, 24, 173 Translational, 16, 24, 33, 173 Trauma, 149, 160, 173 Treatment Failure, 33, 173 Trisomy, 139, 173 Trypsin, 7, 148, 173 Tumor marker, 141, 173

Tumor model, 29, 173 Tumor suppressor gene, 157, 162, 173 U Ulcer, 101, 135, 161, 163, 171, 173 Ulceration, 86, 103, 125, 173 Ulcerative colitis, 16, 22, 173 Ultrasonography, 32, 173 Unconscious, 154, 173 Urea, 140, 162, 173 Urethra, 166, 174 Urinary, 35, 173, 174 Urinate, 174 Urine, 141, 174 Uterus, 30, 143, 145, 148, 172, 174 V Vaccine, 166, 174 Vagina, 143, 144, 174 Vagotomy, 42, 174 Varicella, 106, 174 Vascular, 30, 148, 155, 161, 174 Vasodilators, 161, 174 VE, 23, 65, 174 Vein, 161, 174 Venous, 166, 174 Veterinary Medicine, 119, 174 Virulence, 21, 172, 174 Virulent, 19, 174 Virus, 33, 140, 173, 174, 175 Visceral, 55, 174 Vitro, 24, 36, 54, 155, 172, 174 Vivo, 6, 9, 15, 17, 20, 24, 28, 29, 30, 35, 36, 64, 70, 155, 174 Void, 36, 174 W Waist circumference, 18, 174 Weight Gain, 83, 87, 175 White blood cell, 139, 152, 156, 157, 160, 164, 175 Windpipe, 163, 175 Womb, 174, 175 X Xenograft, 139, 173, 175 X-ray, 150, 160, 161, 167, 175 Y Yeasts, 164, 175 Z Zoster, 106, 175

Index 185

186


Index 187

188


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