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

GALLSTONES 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 ©2003 by ICON Group International, Inc. Copyright ©2003 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., 1960Gallstones: 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: 0-597-83920-4 1. Gallstones-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 gallstones. 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 GALLSTONES ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Gallstones.................................................................................... 17 E-Journals: PubMed Central ....................................................................................................... 30 The National Library of Medicine: PubMed ................................................................................ 31 CHAPTER 2. NUTRITION AND GALLSTONES ................................................................................... 51 Overview...................................................................................................................................... 51 Finding Nutrition Studies on Gallstones .................................................................................... 51 Federal Resources on Nutrition ................................................................................................... 59 Additional Web Resources ........................................................................................................... 59 CHAPTER 3. ALTERNATIVE MEDICINE AND GALLSTONES ............................................................. 61 Overview...................................................................................................................................... 61 National Center for Complementary and Alternative Medicine.................................................. 61 Additional Web Resources ........................................................................................................... 68 General References ....................................................................................................................... 74 CHAPTER 4. CLINICAL TRIALS AND GALLSTONES ......................................................................... 75 Overview...................................................................................................................................... 75 Recent Trials on Gallstones ......................................................................................................... 75 Keeping Current on Clinical Trials ............................................................................................. 75 CHAPTER 5. PATENTS ON GALLSTONES ......................................................................................... 77 Overview...................................................................................................................................... 77 Patents on Gallstones................................................................................................................... 77 Patent Applications on Gallstones............................................................................................... 95 Keeping Current ........................................................................................................................ 101 CHAPTER 6. BOOKS ON GALLSTONES ........................................................................................... 103 Overview.................................................................................................................................... 103 Book Summaries: Federal Agencies............................................................................................ 103 Book Summaries: Online Booksellers......................................................................................... 104 The National Library of Medicine Book Index ........................................................................... 106 Chapters on Gallstones .............................................................................................................. 107 CHAPTER 7. MULTIMEDIA ON GALLSTONES ................................................................................ 113 Overview.................................................................................................................................... 113 Video Recordings ....................................................................................................................... 113 Bibliography: Multimedia on Gallstones ................................................................................... 114 CHAPTER 8. PERIODICALS AND NEWS ON GALLSTONES ............................................................. 117 Overview.................................................................................................................................... 117 News Services and Press Releases.............................................................................................. 117 Newsletter Articles .................................................................................................................... 121 Academic Periodicals covering Gallstones ................................................................................. 122 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 123 Overview.................................................................................................................................... 123 U.S. Pharmacopeia..................................................................................................................... 123 Commercial Databases ............................................................................................................... 124 Researching Orphan Drugs ....................................................................................................... 124 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 129 Overview.................................................................................................................................... 129 NIH Guidelines.......................................................................................................................... 129 NIH Databases........................................................................................................................... 131 Other Commercial Databases..................................................................................................... 134

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The Genome Project and Gallstones........................................................................................... 134 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Finding Associations.................................................................................................................. 147 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 149 Overview.................................................................................................................................... 149 Preparation................................................................................................................................. 149 Finding a Local Medical Library................................................................................................ 149 Medical Libraries in the U.S. and Canada ................................................................................. 149 ONLINE GLOSSARIES................................................................................................................ 155 Online Dictionary Directories ................................................................................................... 157 GALLSTONES DICTIONARY.................................................................................................... 159 INDEX .............................................................................................................................................. 217

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

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

Nonsurgical Management of Gallstone Disease Source: Gastroenterology Clinics of North America. 28(1): 133-144. March 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Cholelithiasis (gallstones) is a common disease in the U.S., associated with significant morbidity. This article reviews the nonsurgical management of gallstone disease. Surgical treatment with cholecystectomy has been increasing with a significant cost to the health care system and is not without risk. The authors maintain that cholecystectomies are often performed unnecessarily in gallstone patients with nonspecific symptoms. Although cholecystectomy is the mainstay of gallstone treatment, nonsurgical treatment alternatives, such as bile acid therapy, topical

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dissolution, and extracorporeal shock wave lithotripsy (if available) may be used in selected patients. In some cases, in particular in the elderly and in other patients at increased risk from surgery, nonsurgical management offers lower morbidity and mortality than does operative treatment. The authors conclude that the decision for surgical versus nonsurgical management should be based on both objective selection criteria and patient choice. 94 references. (AA-M). •

Prospective Study of Coffee Consumption and the Risk of Symptomatic Gallstone Disease in Men Source: JAMA. Journal of American Medical Association. 281(22): 2106-2112. June 9, 1999. Summary: Coffee has several metabolic effects that could reduce the risk of gallstone formation. This article reports on a study undertaken to examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. The authors used data from the Health Professionals Follow Up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 (as part of the 131 item food frequency questionnaire given to United States male health professionals with followup through 1996). The participants included a total of 46,008 men, aged 40 to 75 years in 1986, without history of gallstone disease. The main outcome measures were newly symptomatic gallstone disease or a cholecystectomy (gallbladder removal). During 404,166 person years of followup, 1,081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consumer regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 and for those who drank 4 or more cups per day the RR was 0.55. All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake. In contrast, decaffeinated coffee was not associated with a decreased risk. The authors conclude that, in this cohort of U.S. men, coffee consumption may have helped to prevent symptomatic gallstone disease. 4 tables. 49 references.

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Rapid Dissolution of Gallstones by Methyl Tert-Butyl Ether Source: Journal of Lithotripsy and Stone Disease. 3(1): 62-65. January 1991. Summary: Dissolution of gallbladder or bile-duct stones has received increasing interest in the past decade. This article reviews the rapid dissolution of gallstones by methyl tertbutyl ether (MTBE). MTBE is an ether that remains liquid at body temperature and has dissolved multiple human gallstones implanted in dog gallbladders, within 4 to 6 hours and without serious side effects. This article reports on initial studies of MTBE in humans. The authors describe two patients in whom MTBE was used to dissolve cholesterol gallstones in the gallbladder and bile duct within hours. 6 figures. 12 references.

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Treating Gallstones: New Weapons in an Old War Source: Hopkins Medical News. 14(1): 11-15. Summer 1990. Summary: Each year in this country, surgeons perform more than 500,000 operations to remove gallbladders inflamed with stones. This article discusses alternatives to traditional gallstone surgery, the laparoscopic cholecystectomy and extracorporeal shockwave lithotripsy (ESWL). Through the story of one patient, the author describes

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the procedure, equipment used, and postoperative care required for the laparoscopic cholecystectomy. In addition, the technique of ESWL is described, with an emphasis on the patient benefits and drawbacks. Other endoscopic techniques are briefly described. Two sidebars investigate the causes of gallstones and the treatment of a disease called sclerosing cholangitis. •

Shock-Wave Lithotripsy in Gallstones and Bile Duct Stones: Long-Term Evaluation of Extracorporeal Shock-Wave Lithotripsy for Cholesterol Gallstones Source: Journal of Gastroenterology and Hepatology. 16(1): 93-99. January 2001. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Extracorporeal (outside the body) shock wave lithotripsy (ESWL) is a treatment for gallstones that preserves the gallbladder. Problems after ESWL treatment can include stone recurrence and the development of biliary symptoms. This article reports on a study of 262 patients with cholesterol type gallstones (the best indication for ESWL treatment) who underwent ESWL and 42 control patients with cholesterol type gallstones who received no treatment. The authors evaluated the factors associated with recurrence of gallstones after stone clearance and the development of biliary symptoms after ESWL treatment. The 3, 5, and 7 year cumulative probabilities of gallstone recurrent were 20.6, 27.1, and 33.1 percent, respectively, with the recurrence probability significantly lower in patients with good gallbladder contractility. In patients with recurrence, treatment with ursodeoxycholic acid (UDCA, given orally) was effective. In 69 patients with residual gallstones, the 3, 5, and 7 year cumulative risks of biliary symptoms were 17.3, 24.9, and 30.5 percent, respectively. With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a smaller than 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL. The risk of biliary symptoms was significantly lower in ESWL treated patients with residual stones who had a less than 3 mm fragment size after treatment, compared with control patients. The authors conclude that UDCA was effective in clearing stones in patients with gallstone recurrence. In patients with residual stones, the fragmentation of stones to less than 3 mm and UDCA administration effectively reduced the risk of subsequent biliary symptoms. 3 figures. 4 tables. 18 references.

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Advances in Gallstone Research: A Productive Symbiosis of Basic Science and Clinical Investigation Source: Seminars in Liver Disease. 10(3): [p. 1-3]. 1990. (NOTE: Needs pagination!). Summary: Few areas in medical science have benefited from a wider spectrum of investigation and progress than gallstones. This brief article, an introduction to a series of nine articles on gallstone research, discusses the symbiosis of basic science and clinical investigation that surrounds cholelithiasis. The author discusses the progress in gallstone research; the risk factors, prevalence, and natural course of gallstones; and the dimensions of gallstone disease as a major public health problem. Treatment methods, including extracorporeal shock-wave lithotripsy and oral bile acid dissolution therapy, are introduced. The author concludes that the search for new medical therapies for gallstones is likely to continue successfully as the basic understanding of the pathophysiology of cholelithiasis advances and more is learned about the optimal use of oral bile acid dissolution therapy, lithotripsy, topical cholelithiasis, and surgery.

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Ethnic Variation in Gallstone Disease Source: Practical Gastroenterology. 26 (6): 33-34, 36, 39-40, 42-43, 47-48. June 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Gallstone disease (GSD) is a major cause of morbidity (illness) worldwide. This article considers the epidemiologic data that are now available from a large number of European and American studies demonstrating a marked variation in overall gallstone prevalence among different ethnic groups. These studies have revealed a much higher prevalence of GSD in Native Americans (especially Pima Indians), Chileans, and Mexican Americans, while Japanese and non Hispanic black populations have some of the lowest prevalence of GSD. For example, in women older than 65, the prevalence of GSD among Pima Indians is 89.5 percent, 44.1 percent among Mexican Americans, 16.4 percent among Caucasians, and only 9.5 percent among Japanese. Although the reasons behind this ethnic variation are not well understood, it is important that health care providers be aware that certain ethnic groups are at higher risk for gallstone disease so that appropriate evaluation and timely treatment can be rendered. 4 tables. 36 references.

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Relation of Physical Activity to Risk for Symptomatic Gallstone Disease in Men Source: Annals of Internal Medicine. 128(6): 417-425. March 15, 1998. Summary: Gallstone disease is a major source of morbidity in the United States Gallstones are twice as common in women as in men, but severe biliary events leading to surgery occur with equal frequency in both sexes. This article reports on a study undertaken to determine whether physical activity decreases the risk for symptomatic gallstone disease in men. This prospective cohort study of U.S. male health professionals followed 45,813 men (aged 40 to 75 years) from 1986 to 1994. Questionnaires mailed every 2 years asked about physical activity, incidence of gallstone disease, age, body weight, dietary and alcohol intake, smoking habits, use of medications, and occurrence of diagnosed medical conditions other than gallstone disease. A total of 828 men reported having newly symptomatic gallstones (diagnosed by ultrasonography or radiography) or undergoing cholecystectomy for recent symptoms. After adjustment for multiple confounders, increased physical activity was inversely related to risk for symptomatic gallstone disease. By contrast, sedentary behavior was positively related to risk for symptomatic gallstone disease. Men who watched television more than 40 hours a week had a higher risk for symptomatic gallstones than men who watched less than 6 hours per week. The article concludes that physical activity may play an important role in preventing symptomatic gallstone disease as well as in controlling body weight. The results of this study indicate that 34 percent of cases of symptomatic gallstone disease in men could be prevented by increasing exercise to 30 minutes of endurance-type training five times a week. 5 tables. 62 references. (AA-M).

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Non-Surgical Treatment for Gallstone Pancreatitis Source: Current Topics in Gastroenterology. March 1992. p. 4. Summary: Gallstone pancreatitis is a painful and potentially serious condition caused by gallstones passing from the gallbladder and causing inflammation of the pancreas. This article reports on the use of a non-surgical treatment for gallstone pancreatitis: endoscopic retrograde cholangiopancreatography (ERCP), with sphincterotomy. The article discusses patient selection, indications for the procedure, the techniques used,

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and the results obtained in a group of 15 patients who were treated with this technique. The researchers conclude that ERCP with sphincterotomy is a safe alternative to gallbladder surgery in high risk patients with gallstone pancreatitis. •

Cholelithiasis: New Options for Diagnosis and Treatment of its Complications Source: Senior Patient. 3(1): 42, 44-46. January-February 1991. Summary: Gallstones (cholelithiasis) often produce no symptoms, and their discovery may simply be a matter of chance. In addition, elderly patients often have coexisting age-related illnesses that make diagnosis of cholelithiasis and its resulting complications difficult. This article explores new options for the diagnosis of cholelithiasis and for treatment of its complications. Noninvasive diagnostic techniques overviewed include ultrasonography, abdominal x-ray, computed tomography, cholescintigraphy, oral cholecystography, and intravenous cholangiography. Invasive diagnostic procedures described include endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography. Treatments discussed include stone-dissolving agents, lithotripsy, and laparoscopic surgery. A sidebar discusses risk factors for gallstone disease. 9 references.

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Gallstones, from Gallbladder to Gut: Management Options for Diverse Complications Source: Postgraduate Medicine. 108(3): 143-146, 149-153. September 1, 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Gallstones may be incidental and asymptomatic or painful and accompanied by life threatening obstruction or infection. A thorough knowledge of potential complications is therefore critical, especially because some asymptomatic stones require prompt treatment. In this article, the authors offer guidelines for recognizing and treating the various manifestations of gallstone disease (cholelithiasis). Once the gallstones become symptomatic, surgical removal of the gallbladder (cholecystectomy) is usually recommended. Endoscopic retrograde cholangiopancreatography (ERCO) with sphincterotomy and stone extraction is performed if bile duct stones are evident on imaging studies or suspected on the basis of the clinical picture or liver enzyme abnormalities. In patients with cholangitis (a consequence of bacterial infection superimposed on an obstructed biliary system), the mainstay of therapy is biliary drainage, which should be performed as early as possible, even before determining and treating the cause of obstruction. In selected patients with gallstone pancreatitis, use of early ERCP, sphincterotomy, and stone extraction results in lower morbidity (illness) and mortality (death). Nonsurgical treatment is appropriate for patients with recurrent biliary colic or chronic cholecystitis (gallbladder infection), but not for those with acute cholecystitis. Recurrence rates are high with nonsurgical treatment. 3 figures. 29 references.

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Direct Approach to Gallstones: Percutaneous Cholecystoscopy and Gallbladder Cannulation Source: Practical Gastroenterology. 15(4): 13-15, 24. April 1991. Summary: In addition to the endoscopic intervention in patients undergoing laparoscopic cholecystectomy, endoscopists have had some experience in a direct approach to gallstones. This article discusses two such approaches that have been used:

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direct gallbladder cannulation at the time of endoscopic retrograde cholangiopancreatography (ECRP) with subsequent stone dissolution using a nasogallbladder drain, and direct cholecystectomy with stone fragmentation, extraction, or dissolution therapy via a percutaneous tract. Both modalities have seen limited clinical application. The author concludes that neither will have a significant future unless a cost-effective agent to prevent gallstone recurrence is developed, or chemical cholecystectomy proves both safe and effective. 4 figures. 1 table. 16 references. (AA-M). •

Surgical Treatment of Gallstones in the Geriatric Patient Source: Geriatric Medicine Today. 9(10): 41-50, 59. March 1990. Summary: In considering biliary surgery for the elderly, dramatic changes and new diagnostic and therapeutic advances justify reevaluation of surgical policies. So contends the author of this article that discusses the surgical treatment of gallstones in the geriatric patient. The author considers preoperative evaluation, preparation for surgery, and the anticipated results of surgery for biliary tract disease. Cholecystectomy for cholelithiasis is the most commonly performed major abdominal operation in the geriatric age group. The author concludes that current evidence strongly favors early and definitive surgery, in order to accomplish reasonable morbidity and mortality rates. 3 tables. 17 references.

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Treatment of Gallstones Source: Annals of Internal Medicine. 119(7 Part 1): 606-619. October 1, 1993. Summary: In this article, the author reviews the risks and benefits of therapy for asymptomatic and symptomatic persons with gallstones who are considering therapy to prevent future episodes of biliary pain or complications including acute cholecystitis, pancreatitis, or gallbladder cancer. The author reviews the English-language literature about the natural history of gallstones and the operative mortality rates for open cholecystectomy and laparoscopic cholecystectomy. Mathematical simulation modeling was used to derive estimates of lifetime risks for gallstone-related mortality and for life expectancy, for prophylactic cholecystectomy and expectant management, for men and women of different ages. Results showed that, for persons with asymptomatic gallstones, natural history is so benign that treatment is generally not recommended. The authors conclude that prophylactic cholecystectomy should be recommended for most persons with symptomatic gallstones unless the person wants to try a period of watchful waiting to see if pain recurs. Nonsurgical therapy may be suitable for persons with high operative risk. 1 figure. 11 tables. 92 references. (AA- M).

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Lithotripsy: A New Approach for Gallstones Source: Today's O.R. Nurse. 12(3): 42-44. March 1990. Summary: Technology and the advent of new drug therapy have advanced the choices for treatment of gallstones. This technical article discusses external shockwave lithotripsy as one effective, safe method for the treatment of biliary stones. The bulk of the article presents 10 figures that illustrate the gallbladder; the lithotripter; the set-up of the treatment room; and before, during, and after sonograms of a typical gallstone lithotripsy session. In addition, the authors note the patient criteria, the processes followed, and the results at one lithotripsy facility. The authors conclude that the advances in technology, ultrasound imaging, and operator skills can only enhance the benefits that are offered to the patient with gallstones. External shockwave lithotripsy

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can be beneficial to carefully selected patients and may soon be considered routine treatment for this population. 6 references. •

Gallstone Disease in Mestizo Hispanics (editorial) Source: Gastroenterology. 115(4): 937-946. October 1998. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The etiology of cholesterol gallstones is multifactorial, with genetic and environmental interactions. This editorial comments on another article in the same journal that reports on a study of aborigine cholesterol lithogenic (gallstone creating) genes in Chileans, a population with a high prevalence of gallstones. The researchers concluded that cholesterol lithogenic genes appear widely spread among Chilean Indians and Hispanics. These genes could determine the early formation of gallstones and explain the high prevalence of gallbladder diseases among some South American populations. The author of this commentary article considers the concepts of genetic admixture, noting that some U.S. Hispanic subgroups, most notably Mexican Americans, are known to have a mestizo (mixed) genetic heritage. The author questions whether the high degree of Amerindian admixture among the mestizo Hispanics may have limited the researchers ability to delineate differences in prevalence among age and sex subgroups. The author also reports on a few other related studies and concludes by calling for further research that will help develop a practical means to prevent the formation of stones. 26 references.

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Epidemiology of Gallstones: Prevalence of Gallstone Disease in Iran Source: Journal of Gastroenterology and Hepatology. 16(5): 564-567. May 2001. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: The prevalence of gallstone disease varies depending on the geographic region involved. Few studies, in Asia but not from Iran, about the frequency of gallstone disease have been published. This article reports on a study of the prevalence of gallstone disease in Iran. The study included 477 nomads from southern Iran, 513 industrial laborers older than 34 years, and 421 laborers from a pharmaceutical company above 30 years of age, and 471 elderly persons from three nursing homes near Tehran underwent abdominal sonography. There was a total of 1,373 men and 509 women. Gallstone disease was present in 89 subjects; 10.1 percent of them had undergone cholecystectomy (removal of the gallbladder). While the prevalence in the men and women in the age group 31 to 40 years was very low (0.3 percent in men and 1.8 percent in women), it increases sharply in men older than 60 years and women older than 50 years to more than 10 fold (12.5 and 24.6 percent in males and females aged 71 to 80 years, respectively). The author concludes that, in Iran, gallstone disease is very uncommon in middle aged people, but increases sharply in older people. However, this does not reach the high prevalence seen in Western countries. The intake of a high fiber containing diet, and low numbers of overweight people, smoking habits, and hyperlipidemia (elevated concentrations of fats in the blood) are probably the cause for this low prevalence. 2 tables. 44 references.

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Gallstones in Elderly Patients: Impact of Laparoscopic Cholecystectomy Source: Canadian Journal of Gastroenterology. 14(11): 929-932. December 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: The use of laparoscopic cholecystectomy (LC, removal of the gallbladder) in elderly patients may pose problems because of their poor general condition, especially of cardiopulmonary (heart and lung) function. Moreover, these patients present with acute cholecystitis (inflammation of the gallbladder) and associated common bile duct stones more often than their younger counterparts. In this article, the authors report on their experience from 1990 to 1999 when they performed 943 LCs; 31 (3.2 percent) were attempted on elderly patients, 11 (35 percent) of which were on an emergency basis because of acute cholecystitis, cholangitis (bile duct inflammation) or acute biliary pancreatitis. Ten percent of LCs needed to be converted to an open cholecystectomy, most often because of an increase in the partial pressure of carbon dioxide in the blood produced by excessive operative time. A gasless procedure (LC usually uses gas to increase the abdominal cavity for access and visualization purposes) was used in the last three years of the study on eight cases; the overall rate of conversion from LC to open cholecystectomy in this group was 0 percent. Associated gallbladder and common bile duct stones were found in five (16 percent) patients. The success rate was 100 percent, overall morbidity was 29 percent and there was no mortality. The authors conclude that their results show that LC is a feasible and safe procedure for use in elderly patients. Gasless LC should be preferred in patients classified as American Society of Anesthesiologists' class III. 4 figures. 21 references.

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Principles and Theory of Gallstone Lithotripsy Source: Endoscopy Review. 7(6): 28-29, 33-35. July-August 1990. Summary: This article addresses techniques for the noninvasive treatment of gallstones by lithotripsy. In particular, the article defines shock waves, how they are generated and focused, and how gallstone fragments are cleared from the gallbladder. Shock waves or acoustic waves are generated by various lithotripters: spark gap, electromagnetic, and piezoelectric. The theoretical principle of each technique is explained as is focusing, which varies according to the method used. Fragmentation of the stone is hypothesized as being the result of cavitation forces on the stone's surface; this differs from earlier theories which held that shock waves interacted with the stone because the stone's acoustic impedance differed from bile. Fragmentation quality of various type stones are discussed: radiolucent cholesterol, calcified versus noncalcified, pigment versus cholesterol, and others. Dissolution of fragments is also addressed, particularly why complete clearance rates differ among patients and what role bile salts play in improving clearance. A glossary of terms is provided.

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Pros and Cons of Surgical and Non-Surgical Therapy for Gallstones Source: Endoscopy Review. 7(6): 36, 38. July-August 1990. Summary: This article addresses the advantages and disadvantages of cholecystectomy, as well as nonsurgical therapy including oral medication and lithotripsy. Cholecystectomy not only eliminates symptoms, but eliminates any possibility of recurrent stones forming. Its disadvantages include mortality, estimated at one in 1,000 for persons under 50 years, and one in 1,500 for those over 50 years. Nonsurgical techniques are recommended for those over age 60. Other disadvantages include such

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complications as thrombophlebitis, pneumonia, atelectasis, or transient ileus. Another complication is postcholecystectomy syndrome, in which the patient returns complaining of the same symptoms as before the gallbladder and stones were removed. Nonsurgical therapy eliminates incisional pain, hospitalization, and home recovery time. Lithotripsy requires ursodiol therapy and follow-up care, which amount to additional costs. Based on economics, it is concluded that cholecystectomy may be more cost-effective over a longer period of time. This potential benefit, however, must be balanced against the potential decrease of mortality and morbidity with lithotripsy versus surgery, as well as savings in time lost from work. •

Gallstone Symptoms: Myth and Reality Source: Postgraduate Medicine. 90(5): 119-122, 124, 126. October 1991. Summary: This article attempts to separate myth and reality in regards to gallstone symptoms. The author discusses why the classic description of biliary colic is inaccurate and why the traditional belief that gallstones cause flatulent dyspepsia persists in spite of convincing evidence to the contrary. The author summarizes data from recent controlled trials, cross-sectional population studies, and large prospective case series and reassesses the accuracy of the traditional description of gallstone symptoms. The author also defines the symptoms' relationship to the syndromes of flatulent dyspepsia and biliary colic. 2 tables. 30 references. (AA-M).

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Commentary: Rapid Dissolution of Gallstones in Humans Using Methyl Tert-Butyl Ether Source: Journal of Lithotripsy and Stone Disease. 3(1): 58-61. January 1991. Summary: This article comments on the first report of the clinical use of methyl tertbutyl ether (MTBE) to dissolve gallbladder and bile duct gallstones (simultaneously published with this commentary). The author presents a brief history of the use of dissolution therapy, the introduction of ether solvents, the use of an automatic infusionaspiration pump, and a comparison of dissolution therapy to laparoscopic cholecystectomy. An annotated bibliography of 6 related items is appended. 19 references.

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Current Options in Gallstone Management: What to Do When Symptoms are Mild or Absent Source: Postgraduate Medicine. 95(5): 115-118, 121, 125, 128. April 1994. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This article considers the current options in gallstone management, focusing on the course of action when symptoms are mild or absent. The article provides information about the types of gallstones and their causes; the clinical manifestations of gallstones; natural history of gallstones; treatment options, including oral dissolution therapy, gallstone lithotripsy, contact dissolution therapy, and surgical therapy; and managing asymptomatic patients, patients with moderate symptoms, and patients with mild symptoms. The author stresses that most patients with gallstones are asymptomatic and, for them, expectant management is now recommended by many authorities. 33 references.

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Physical and Metabolic Factors in Gallstone Pathogenesis Source: Gastroenterology Clinics of North America. 28(1): 75-97. March 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article discusses metabolic factors underlying the secretion of supersaturated bile, and physical factors allowing the solubilization and precipitation of the biliary lipids and calcium salts that constitute gallstones. Gallstones are divided into three major types: cholesterol, black pigment, and brown pigment, depending on their composition, and hence, on their pathogenesis. Gallstones form as the culmination of a complex series of events that begin when insoluble lipids and inorganic salts secreted by the liver are not solubilized normally by the detergent properties of bile salts. This occurs when metabolic events produce bile containing excess amounts of either cholesterol or bilirubin, both of which are relatively insoluble in aqueous solution. In addition, physical factors must allow rapid nucleation within the resident time of bile in the biliary tree. For cholesterol gallstones, metabolic alterations in hepatic (liver) cholesterol secretion combine with changes in gallbladder motility and intestinal bacterial degradation of bile salts to destabilize cholesterol carriers in bile and produce cholesterol crystals. For black pigment gallstones, changes in heme metabolism or bilirubin absorption lead to increased bilirubin concentrations and precipitation of calcium bilirubinate. In contrast, mechanical obstruction of the biliary tract is the major factor leading to bacterial degradation and precipitation of biliary lipids in brown pigment stones. 7 figures. 136 references. (AA-M).

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Role of Surgery in the Management of Gallstones Source: Seminars in Liver Disease. 10(3): 222-231. 1990. Summary: This article discusses the role of surgery in the management of gallstones. The author presents a review of current surgical indications for operative management of biliary stones, as well as the associated morbidity and mortality, and compares these results to the newer nonsurgical treatment modalities. This article is not intended to describe surgical technique in particular but offers treatment options for gallstone disease in the 1990s including surgery. Specific topics discussed include the assessment of risk for surgical therapy, complications of gallstones, postcholecystectomy syndrome, gallstone pancreatitis, cholangitis, and common duct stones. 13 tables. 101 references.

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CT Imaging of Gallstones: What Does It Really Add? Source: Applied Radiology. 19(10): 22-25. October 1990. Summary: This article discusses the usefulness of computed tomography (CAT) scans for imaging gallstones. Because treatment with extracorporeal shock wave lithotripsy (ESWL), oral bile acid therapy, and percutaneous dissolution therapy are generally reserved for stones that are predominantly cholesterol, it is useful to predict gallstone composition. However, the degree of precision needed in assessing gallstone composition for therapeutic triage is unknown. To date, most interest has focused on the use of CAT for distinguishing cholesterol from pigment stones. The authors conclude that despite some early enthusiasm, the problem has proven exceptionally complex. 5 tables. 17 references.

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Nonsurgical Treatment of Cholelithiasis: An Analysis of Clinical Opportunity Source: International Journal of Technology Assessment in Health Care. 6(4): 643-654. 1990. Summary: This article examines the potential impact of on patient care and resourc e utilization of recently developed nonsurgical treatments for gallstones. Using epidemiological and efficacy data from the literature and current patient selection criteria, the authors evaluate ursodeoxycholic acid (UDCA), extracorporeal shock-wave lithotripsy, and direct instillation of methylterbutyl ether in terms of short-term clinical results, health policy, and economic implications. 2 figures. 3 tables. 37 references. (AA).

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Gallstone Disease: Update on Diagnostic and Therapeutic Options Source: Consultant. 37(8): 2049-2052, 2057-2058. August 1997. Contact: Available from Consultant. Cliggott Publishing Company, 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article guides readers to the recommended diagnostic and therapeutic strategies for patients with gallstone disease. The author describes the indications, benefits, and drawbacks of open and laparoscopic cholecystectomy. The author also addresses the diagnosis and management of bile duct stones, acute cholecystitis, and gallstone pancreatitis. A brief discussion of therapeutic options, including oral dissolution, follows. Ultrasonography of the right upper quadrant is the best diagnostic test for patients with symptomatic gallstones. Laparoscopic cholecystectomy has replaced open cholecystectomy as the standard therapy for such patients. Its advantages include less postoperative pain, shorter length of hospitalization, and earlier return to normal activity; the most serious disadvantage is possible injury to the bile ducts during surgery. Persistently elevated bilirubin and alkaline phosphatase values indicate bile duct obstruction; endoscopic retrograde cholangiography can confirm the diagnosis. If bile duct stones are present, endoscopic sphincterotomy and stone extraction are performed. Cholescintigraphy is used to confirm the diagnosis of acute cholecystitis. Patients with this disorder should be hospitalized and receive a broad-spectrum antibiotic and intravenous fluids; laparoscopic cholecystectomy should be performed as soon as the patient's condition is optimized. Oral dissolution has low efficacy and is indicated only for patients at high risk for surgical complications or for those who refuse surgery. 2 figures. 1 table. 16 references. (AA-M).

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Gallstones: Consider the Options Source: Patient Care. 24(17): 28-34, 39-42, 47. October 30, 1990. Summary: This article guides the physician in helping patients and their health care teams choose wisely among the many options for treating gallstones. Topics include oral dissolution therapy, the technique of laparoscopic cholecystectomy, some pros and cons of cholecystectomy, extracorporeal shock wave lithotripsy, and percutaneous, contact, and endoscopic therapies. The author concludes that laparoscopic cholecystectomy, while still only a tiny proportion of all cholecystectomies performed, will soon be the procedure of choice for both patient and surgeon. A patient care flowchart for treating gallstones is included. 2 figures. 24 references.

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Guidelines for the Treatment of Gallstones Source: Annals of Internal Medicine. 119(7): 620-622. October 1, 1993.

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Summary: This article presents a series of guidelines for the treatment of gallstones. The authors note that proper decision-making for gallstone disease requires the recognition of three categories of disease: asymptomatic disease; symptomatic disease; and complications of gallstone disease, such as acute cholecystitis and gallbladder cancer. This guideline focuses on the first two categories only. Topics covered include therapy choices; background, symptoms, and diagnosis; gallbladder cancer; recommendations for preventing future problems arising from gallbladder disease; recommendations for treating asymptomatic gallstones; and recommendations for treating symptomatic gallstones. The article refers readers to numbered sections in an accompanying review article in the same journal issue. •

Gallstones and Diabetes: A Case-Control Study in a Free-Living Population Sample Source: Hepatology. 25(4): 787-790. April 1997. Summary: This article reports on a case-control study to determine the prevalence of diabetes mellitus in a group of subjects with gallstones or who have undergone cholecystectomy (cases). The authors compared these subjects with a control group of subjects without gallstones, selected during an epidemiological study. The subjects were matched for sex, age, and body mass index; there were 336 cases and 336 controls, aged 30 to 69 years. All subjects with fasting glycemic levels of less than 140 mg per dL and without a documented history of diabetes were submitted to a simplified oral glucose tolerance test (OGTT) and then classified according to the National Diabetes Data Group criteria. The prevalence of diabetes in the subjects affected by gallstone disease was significantly higher than that in controls (11.6 percent versus 4.8 percent). Diabetes was more frequent in subjects with gallstone disease than in the control group, even according to sex (18.3 percent versus 9.9 percent for men; 9.3 percent versus 2.6 percent for women). The authors conclude that an altered glucose metabolism may increase the risk of developing cholelithiasis in certain subjects. 3 tables. 36 references. (AA-M).

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Gallbladder Stone Recurrence After Medical Treatment: Do Gallstones Return True to Type? Source: Digestive Diseases and Sciences. 40(12): 2568-2575. December 1995. Summary: This article reports on a study of gallbladder stone recurrence after medical treatment in 21 patients with recurrent stones. The new stones were detected 5 to 74 months after patients' stones were eradicated using dissolution therapy (n = 15) or percutaneous cholecystolithotomy (n = 6). The authors compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores (measured by computed tomography), and the dissolvability of the recurrent stones with oral bile acids and/or extracorporeal shock-wave lithotripsy. Before treatment, 5 patients had single stones; 16 patients had multiple stones. On recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. The authors concluded that gallbladder stones do not recur true to type in up to two-thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio-and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids. 3 figures. 1 table. 65 references. (AA-M).

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Risk of Symptomatic Gallstones in Women with Severe Obesity Source: American Journal of Clinical Nutrition. 55(3): 652-658. March 1992. Summary: This article reports on a study that investigated the risk of symptomatic gallstones in women with severe obesity. Among 90,302 women aged 34-59 at baseline

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followed from 1980 to 1988, 2,122 cases of newly diagnosed symptomatic gallstones occurred. From 1980 to 1986, 488 cases of newly diagnosed unremoved gallstones were documented. The authors note a striking increase in gallstone disease risk with obesity. Recent weight loss was associated with a modestly increased risk after adjustment for body mass index (BMI) before weight loss. Current smoking was an independent risk factor for gallstones. 5 tables. 33 references. (AA-M). •

Asymptomatic Gallstones Revisited: Is There a Role for Laparoscopic Cholecystectomy? Source: Archives of Family Medicine. 2(9): 959-968. September 1993. Summary: This article reports on a study undertaken to compare the mortality effects of prophylactic laparoscopic cholecystectomy with that of expectant management (therapy delayed until gallstone symptoms or complications develop) in persons with asymptomatic gallstones. The study design consisted of decision analytic models of the two clinical strategies, using input data from a review of the published medical literature pertaining to the epidemiology, natural history, and treatment outcomes related to gallstone disease. Results show that the prophylactic laparoscopic cholecystectomy strategy led to fewer gallstone-related deaths than the expectant management strategy, but all of the deaths in the former group occurred earlier in life. Sensitivity analysis demonstrated the superiority of expectant management over a wide range of input assumptions. The authors conclude that prophylactic laparoscopic cholecystectomy should not be routinely recommended for individuals with asymptomatic gallstones. 6 figures. 1 table. 99 references. (AA-M).

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Management of Ductal Gallstones Source: Contemporary Surgery. Volume 37. August 1990. 8 p. Summary: This article reports on a symposium that focused on ductal gallstones and the comparison of various treatment modalities. Two subsets of patients are discussed: patients in whom stones are present in the common duct or common hepatic ducts who have not been operated on specifically for the ductal stones, and patients in whom the stones are defined after cholecystectomy and/or exploration of the common duct. Modalities covered include dissolution and extraction, either by endoscopic retrograde cholangiopancreatography (ERCP) or transhepatically; lithotripsy; and surgery, either endoscopic surgery or operative intervention. 6 references.

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Pathogenesis and Treatment of Gallstones Source: Current Opinion in Gastroenterology. 12(5): 471-476. September 1996. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 700, Philadelphia, PA 19106. (215) 574-2266. Fax (215) 574-2292. Summary: This article reviews recent advances in the pathogenesis and treatment of gallstones. A large number of studies over the past year have dealt with laparoscopic cholecystectomy, particularly the optimal approach to determine whether common bile duct stones are present. There continues to be considerable debate in this regard, although more experience is being gained with intraoperative and postoperative management of these stones. Endoscopic ultrasonography has been studied for this indication. Fewer studies dealing with medical dissolution of gallstones appeared during the past year. Hepatolithiasis has been the topic of a number of studies as awareness of this entity has increased. Finally, refinement of endoscopic techniques for

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removal of common bile duct stones continues, mainly dealing with large, difficult-toremove stones. 1 figure. 2 tables. 51 references (11 annotated). (AA-M). •

Management of Gallstones and Their Complications Source: American Family Physician. 61(6): 1673-1680. March 15, 2000. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article reviews the management of gallstones (cholelithiasis) and their complications. The accurate differentiation of gallstone induced biliary colic (pain) from other abdominal disease processes is the most crucial step in the successful management of gallstone disease. Despite the availability of many imaging techniques to demonstrate the presence of gallstones, clinical judgement ultimately determines the association of symptoms with cholelithiasis and its complications. The authors contend that adult patients with silent or incidental gallstones should be observed and managed expectantly, with few exceptions. In symptomatic patients, the intervention varies with the type of gallstone induced complication. Diagnostic tests reviewed include laboratory tests, ultrasonography, endoscopic retrograde cholangiopancreatography, bile microscopy, computed tomography (CT) and magnetic resonance imaging (MRI), and hepatobiliary scintigraphy. Ultrasound provides more than 95 percent sensitivity and specificity for the diagnosis of gallstones greater than 2 mm in diameter. Ultrasonography of the gallbladder should follow a fast of at least 8 hours because gallstones are visualized better in a distended, bile filled gallbladder. Nonoperative therapies for symptomatic gallstones include oral bile acid dissolution, contact solvents, and extracorporeal shock wave lithotripsy. A patient care algorithm offers management strategy for gallstones. 1 figure. 5 tables. 26 references.

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Gallstones: Alternatives to Surgery Source: RN. Registered Nurse. 53(4): 44-51. April 1990. Summary: This article reviews the non-surgical alternatives available for treating gallstones and the nursing role in each of them. Topics covered include how gallstones form and what their common symptoms are; extracorporeal shock wave lithotripsy; endoscopic stone removal or endoscopic sphincterotomy; contact cholesterol solvents, including, monooctanoin and methyl tertiary butyl ether; and the use of oral bile acids, including chenodiol and ursodiol, for long-term therapy. The post-test for receiving continuing education credits is appended to the article. 4 figures. 1 table. 5 references.

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Recognizing and Managing Cholelithiasis Source: Nursing90. November 1990. p. 32J. Summary: This brief article presents a quick overview for nurses on recognizing and managing cholelithiasis or gallstones. The author covers the signs and symptoms to expect and recommended interventions and treatment. The author also includes the use of a brief case example for illustration of the topics discussed.

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Endoscopic Approach to Cholelithiasis: Overview Source: Practical Gastroenterology. 15(4): 10. April 1991. Summary: This brief article presents an introduction to a three-article series on the endoscopic approach to cholelithiasis. All three mechanical techniques used to treat

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gallstones, i.e., extracorporeal shock wave lithotripsy, lasers, and various agitationsuction devices, require percutaneous or laparoscopic access to the gallbladder and stone fragment extraction or washout. This article also addresses the cost issue, stone recurrence problems, and some of the numerous unanswered questions that plague the field of laparoscopic cholecystectomy. •

Gallstone Formation: Local Factors Source: Gastroenterology Clinics of North America. 28(1): 99-115. March 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This review article discusses factors promoting or inhibiting crystal nucleation and the role of the gallbladder in gallstone formation. Supersaturation of bile is necessary for gallstone formation. However, patients who have undergone a cholecystectomy (gallbladder removal) do not form gallstones. This indicates a role of local factors in gallstone formation. In the absence of a gallbladder, hepatic (liver) bile passes into the duodenum within minutes to hours. With an intact gallbladder, however, bile can be stored in the gallbladder for hours, days, or even weeks. This storage time is essential to allow cholesterol crystals to nucleate, calcium salts to precipitate, and stones to grow. Gallbladder stasis, mucin secretion, the presence of pronucleating and antinucleating biliary proteins, and some medications have been shown to alter gallstone formation. New data have also caused the role of bacterial infection in gallstone pathogenesis to be reexamined. In addition, genetic factors have recently been identified that lead to a change in hepatic bile secretion and may predispose people to gallstone formation. 130 references. (AA-M).

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Gallstone Pancreatitis: Choosing and Timing Treatment Source: Postgraduate Medicine. 89(2): 123-129. February 1, 1991. Summary: Why the passage of small gallstones sometimes causes pancreatitis is still unclear, but the condition leads to life-threatening multisystem dysfunction in some people. This article notes that surgical removal of stones or the gallbladder is often necessary to prevent complications and recurrence. The timing of surgery is dictated by serum enzyme levels and liver function test results as well as by the patient's condition. Whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved. The authors illustrate diagnosis of the disorder with two representative case reports and also address treatment issues. 2 figures. 3 tables. 24 references.

Federally Funded Research on Gallstones The U.S. Government supports a variety of research studies relating to gallstones. 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. 2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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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 gallstones. 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 gallstones. The following is typical of the type of information found when searching the CRISP database for gallstones: •

Project Title: ALIMENTARY TRACT LIPIDS IN HEALTH AND DISEASE Principal Investigator & Institution: Carey, Martin C.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 31-MAR-2004 Summary: Bile formation and secretion control homeostatic mechanisms for eliminating cholesterol and tetrapyrrole molecules form the organism as well as absorption of dietary fat. Bile dysfunction causes several common diseases, including gallstones and cholestasis. This proposal employs biophysical rationale and physical-chemical methodology to further molecular understanding of the physical biochemistry of bile, its formation, secretion and functions. The PI and colleagues will design and study appropriate model systems and correlate the results with pathophysiological phenomena pertaining to the function and dysfunction of native systems. They will use I)novel flurocholesterol methodology, cryoelectron microscopy and electron energy-loss spectroscopy to elucidate physical-chemical pathways whereby cholesterol molecules are transferred from blood to liver cell and bile, ii) characterize interactions of bile salt molecules with sphingomyelin in micellar solutions and at interfaces related to cholesterol secretion, absorption and apoptosis, iii) determine the physical-chemical origin and pathophysiology of lipoprotein X in bile secretory failure, iv) define how phosphatidylcholine, cholesterol and calcium influence the physical- chemical state of natural conjugated bilrubins in model (bilrubin ditaurate) and native biles employing analytical ultracentrifugation and spectrophotometric techniques, v) measure the metastable and equilibrium solubilities of unconjugated bilirubin in modelbiles utilizing potentiometric titration and dissolution and correlate the information pathophysiologically with pigment-stone biles, vi) discover whether humans with ~black~ pigment gallstones have dysfunctional mutations of the ileal bile acid transporter gene. These objectives are designed to advance our understanding of physical chemistry of bile as ell as normal and abnormal movements of cholesterol and billirubin to and from the liver and alimentary tract. The systematic project should lead to new targets and strategies for prevention of pigment and cholesterol gallstone diseases as well as lipid transport abnormalities sin cholestasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BILE SALTS, MEMBRANES, AND CYTOTOXICITY Principal Investigator & Institution: Heuman, Douglas; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2001 Summary: Bile salts adsorb to membranes, at high concentrations causing membrane disruption. Adsorption of bile salts to intracellular membranes may determine many of their physiological effects, and bile salt induced membrane injury may be important in pathogenesis of cholestatic liver disease and gallstones. We have studied the adsorption

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of bile salts to lecithin-cholesterol vesicles and have developed and validated a quantitative model which predicts the distribution of bile salt taurine conjugates in mixed bile salt solutions between lecithin-cholesterol bilayers and the aqueous phase. In the studies proposed, this model will be generalized to a broad array of bile acids and other organic anions, membrane lipids, and solution conditions. Using large unilamellar vesicles of varying lipid composition, we will examine the relationship between membrane binding of bile salts, mixed micellar dissolution of membrane lipids (observed with quasielastic light scattering) and altered membrane permeability (release of trapped soluble markers assessed by ultrafiltration) to determine if the mixed micellar threshold concentration and the permeation threshold at which membrane leakage begins are predictable consequences of the membrane-bound ionized bile salt/lecithin ratio. Pure protein kinase C isoenzymes (alpha, betaII, delta, epsilon) prepared in a baculovirus system will be employed to test the hypothesis that bile salts activate protein kinase C isoenzymes by binding to membranes and serving as a "bridge" between the enzymes and membrane lipids. The model of bile salt-lecithin interactions will be extended beyond the limits of the two phase (monomer-membrane) region into micellar regions of the phase diagram by combining techniques of gel filtration and ultrafiltration, in order to permit modelling of detergent effects of mixed bile salt solutions. Using synthetic vesicles, isolated canalicular plasma membranes, and living cells (erythrocytes, cultured neoplastic gallbladder epithelia) we will test the hypothesis that lecithin in bile normally protects high cholesterol plasma membranes from bile salt injury by depressing the non-lecithin- associated bile salt concentration to non-toxic levels, and that this protective effect declines predictably as the cholesterol content of biliary vesicles increases. Finally the hepatoprotective role of biliary lipids and biliary bile salt-lipid interactions will be studied in two in vivo models of bile salt-induced liver injury: acute infusion of bile salts in the choline deficient bile fistula rat and chronic feeding of bile salts in hamsters fed lithogenic diets. The ultimate goal of these studies is to provide a conceptual framework for understanding the toxic and protective properties of bile salts and the role of bile salt toxicity in human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHOLESTEROL HOMEOSTASIS IN THE INBRED MOUSE Principal Investigator & Institution: Wang, David Q.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The intestine is an unique organ providing dietary and re-absorbed biliary cholesterol to the body. Excess cholesterol can result in cholesterol gallstone disease. Cholelithiasis is prevalent in cultures consuming a Western diet with high cholesterol, and can be induced in mouse models by a high cholesterol and cholic acid diet. Therefore, understanding cholesterol absorption is of great importance to both prevention and treatment of cholesterol gallstones. It has been known that genetic factors apparently play a critical role in the development of cholesterol gallstones in inbred mice. It has been found that differences in gallstone susceptibility between C57L and AKR strains are determined by at least two Lith (gallstone) genes, as well as that the sister of P-glycoprotein (Spgp), a canalicular bile salt transporter is a candidate gene for the Lith1. A recent observation that there is a remarkable positive correlation in eleven strains of inbred mice between percent cholesterol absorption and prevalence of cholesterol gallstones at 8 weeks of feeding the lithogenic diet strongly suggests that the extent of cholesterol absorption from the intestine may be a genetically determined step for cholesterol gallstone formation. Furthermore, it has been observed that there are

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gender differences in susceptibility to cholesterol gallstones, favoring males to females by 2:1. The applicant proposes five specific aims to explore genetic and physiological mechanisms of cholesterol homeostasis as well as molecular mechanisms of cholesterol absorption, and pathophysiological mechanisms of the formation of lithogenic bile and cholesterol cholelithiasis. Aim 1: To investigate genetic variations in cholesterol absorption efficiency and their role in cholesterol gallstone formation among 12 strains of inbred mice. Aim 2: To define differences in molecular mechanisms for cholesterol absorption and chylomicron formation between mice with high and low cholesterol absorption. Aim 3: To study postprandial chylomicron metabolism and its role in the lithogenesis of bile. Aim 4: Using genetically gallstone-susceptible and the SR-B1 att (knockout) mice, to elucidate the role of SR-B 1 (HDL) receptor in biliary cholesterol secretion and cholesterol gallstone formation. Aim 5: To characterize hormonal basis for gender differences in the gallstone phenotypes. These studies should provide important contributions to our basic understanding of cholesterol homeostasis as well as pathogenesis of cholesterol gallstone formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF GALLBLADDER SLUDGE & STONES IN PREGNANCY Principal Investigator & Institution: Lee, Sum P.; Professor and Chief; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2002 Summary: (Adapted from Investigator's Abstract) Without exception, cholesterol gallstone is more common among women than men in every population studied. This consistent and conspicuous gender difference starts during puberty, continues throughout the childbearing years, but fades alter menopause. Biliary sludge, a newly described ultrasonographic diagnosis, is a mixture of cholesterol monohydrate crystals and other precipitates within the gallbladder, and it is regarded as a precursor form of gallstones. Sludge is frequently found in pregnant women, although the risk factors for the development of gallbladder sludge and stones during pregnancy have not been clearly defined. The investigators propose a prospective investigation of gallstones and biliary sludge that develop during pregnancy to accomplish several specific aims. First, they will determine the incidence rate of biliary sludge and gallstones during pregnancy and compare this rate to a nonpregnant control sample. Second, they will look for factors predictive of the development of biliary sludge gallstones during pregnancy, including obesity, age, hyperinsulinemia, hyperlipidemia and serum estradiol and progesterone levels. Lastly, they will examine predictors of persistent gallstones and biliary sludge disease in the postpartum period by following women until one year after delivery. They aim to include as many as 7,280 women in this study. They will be recruited from the prenatal and genealogy clinics of Madigan Army Hospital. Development of gallstones and biliary sludge will be defined by ultrasonographic examination of the gallbladder contents performed at pre-specified intervals during gestation and postpartum, and at an equivalent time in the nonpregnant control group. A variety of analytic methods will be used to achieve these specific aims of this study. Gallstone and biliary sludge are common in women and represent major causes of morbidity. The investigators state that this study will add new and important insight into the risk factors leading to these outcomes and affecting their natural history. They further note that this information, in turn, may lead to effective strategies for treatment and prevention of these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC DETERMINANTS OF CHOLESTEROL GALLSTONES IN MICE Principal Investigator & Institution: Paigen, Beverly J.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 31-MAY-2006 Summary: (Provided by applicant): The goal of this proposal is to identify the genes responsible for cholesterol gallstone formation and their function. Identification of these genes in the inbred mouse may define the pathophysiological mechanisms contributing to disease and may identify key proteins as targets for rational drug design. Aim 1 proposes to use transgenic or knockout technology to prove the identity of three strong candidate genes discovered during the last proposal; Abcb11 for Lith1, Abcc2 for Lith2, and carboxypeptidase E (Cpe), a mutation that results in both obesity and increased gallstone susceptibility. Aim 2 proposes to test promising candidate genes in the remaining QTL regions discovered during the last grant period by comparing the gallstone-resistant and susceptible strains for sequence and expression differences. To find additional genes associated with susceptibility to gallstone formation, aim 3 proposes to carry out a series of crosses between gallstone susceptible and resistant strains. Analysis will include both main QTL and interacting or epistatic QTL using our recently developed statistical methodology. Identifying the full range of QTLs that lead to gallstone disease in the mouse will position the field of cholesterol gallstone research to take advantage of the large genomic sequencing efforts currently underway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC LOCI INFLUENCING HUMAN GALLBLADDER DISEASE Principal Investigator & Institution: Nakeeb, Attila; Surgery; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Attila Nakeeb, M.D. completed his residency training in General Surgery at the Johns Hopkins Hospital (1991-1999) and spent two years as a research fellow (1993-1995) in the laboratory of Dr. Henry A. Pitt investigating biliary malignancies and gallstone pathogenesis. He is currently an Assistant Professor of Surgery at the Medical College of Wisconsin (MCW) and continues to have a strong interest in biliary diseases. Dr. Nakeeb is seeking this Mentored Patient-Oriented Research Career Development Award (K-23) to study the genetic loci influencing human gallbladder disease. The long-term goal of this research focus is to understand the role of genetic pathogenic mechanisms underlying gallbladder dysfunction, which in turn can lead to new strategies to prevent gallstone formation. A career development plan consisting of didactic coursework, participation in national seminars and institutional research meetings, close and frequent interaction with mentors, and completion of the research plan is proposed to allow the mastering of competencies and research skills necessary to become a successful clinical investigator. The environment at MCW is ideally suited to study the genetics of human gallbladder disease. A cohort of 2209 individuals from 509 nuclear families has undergone basic phenotyping for obesity as well as DNA genotyping. A subset of these families are participating in refined obesity phenotyping at MCW, and are available for the determination of gallbladder disease specific phenotypes. The specific aims of this proposal are as follows: 1) To characterize potential endophenotypes related to the risk of developing gallbladder disease including presence of gallstones, size and number of stones, gallbladder wall thickness, and gallbladder response to a fat meal 2) To conduct univariate and

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Gallstones

multivariate quantitative genetic analyses on the phenotypes of gallbladder disease, and 3) To analyze a genome wide scan to identify quantitative trait loci with measurable effects on the expression of gallbladder disease risk factors. The completion of this research plan and the training and knowledge acquired from the mentors should allow Dr. Nakeeb to develop into an independent clinical scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AMERICANS

GENETICS

OF

GALLBLADDER

DISEASE

IN

MEXICAN

Principal Investigator & Institution: Duggirala, Ravindranath; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 15-MAR-2002 Summary: (Adapted from investigator's abstract) Gallbladder disease (GBD) is one of the major causes of morbidity and mortality in the United States. In populations such as the Mexican Americans, the prevalence of GBD is high, and it often clusters with diseases such as non-insulin dependent diabetes mellitus (NIDDM) and obesity. The etiology of GBD is unclear, but it is believed to be multifactorial in origin involving abnormalities of the hepatobiliary system such as supersaturation of bile with cholesterol, changes in cholesterol nucleation, and hypomotility of the gallbladder. Despite the epidemiological evidence for its association with risk factors such as age, sex (higher in women), obesity, native American ancestry, NIDDM, and cardiovascular disease risk factors, evidence for genetic determination of GBD is very limited. The purpose of this project is to conduct a genetic epidemiologic investigation involving molecular genetic data, GBD phenotypes, and statistical genetic techniques to examine the genetic basis for variation in GBD phenotypes in a set of 32 low-income Mexican American families that is currently under investigation in relation to the genetic determination of NIDDM (San Antonio Family Diabetes Study: SAFADS). The overall objectives of this study are to measure genetic effects on GBD phenotypes, and to identify and localized GBD susceptibility genes. The specific aims are 1) to define GBD phenotypes such as gallstone disease (presence of gallstones), gallstone number (solitary versus multiple), gallstone diameter, and gallbladder wall thickness using ultrasonography; 2) to perform genetic analysis in order to estimate heritabilities for GBD phenotypes, to detect initial evidence of linkage to GBD susceptibility loci, to refine the initial screening using multipoint linkage analysis, and to detect linkage or association using non-parametric methods. Ultrasound GBD phenotypic data will be collected from 720 individuals distributes across 32 families. The initial genome screening will be based on a subset of SAFADS families involving 444 subjects for whom the 10-15 centiMorgan (cM) genome map based on more than 360 markers is already available. After detecting potential signals for linkage, a high resolution 5 cM gene map to be obtained from a full set of SAFADS families(720 individuals) will be used to precisely localize susceptibility loci influencing GBD phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHOLESTEROL

HEPATOCELLULAR

MEMBRANE

TRAFFICKING

OF

Principal Investigator & Institution: Cohen, David C.; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 15-MAY-1990; Project End 31-MAR-2007

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Summary: (provided by applicant): Reverse cholesterol transport is the metabolic pathway for movement of cholesterol from peripheral tissues to liver for secretion into bile. Consistent with their central role in reverse cholesterol transport, high density lipoproteins (HDL) are the principal source of biliary cholesterol. Nevertheless, hepatocellular mechanisms for transport and biliary secretion of HDL-derived cholesterol remain poorly understood. Scavenger receptor class B type I (SR-BI) is highly expressed in liver and mediates uptake of HDL lipids as well as cellular cholesterol efflux. Caveolae are cholesterol-and sphingolipid-rich membrane microdomains, which also participate in influx and efflux of cellular cholesterol. Both caveolin-1, the structural protein of caveolae, and SR-BI are expressed on the sinusoidal and canalicular domains of hepatocyte plasma membranes. Using primary cultures of hepatocytes derived from caveolin-1 transgenic mice and mice with targeted disruption of genes encoding caveolin-1 or SR-BI, we will explore contributions of caveolin-1 and SR-BI to hepatocellular uptake of HDL cholesterol, as well as to efflux of free cholesterol from the plasma membrane. Observations in tissue culture will be correlated with measurements of HDL clearance and biliary lipid rates in vivo. Based upon preliminary experiments, which demonstrate colocalization of fluorescence-labeled HDL with SR-BI and caveolin1 in early endocytic vesicles, we will also examine a role for caveolae in trafficking of HDL through the hepatocyte. Real time fluorescence microscopy of HuH-7 hepatoma cells, which have been transfected with a green fluorescent protein-caveolin-1 fusion protein, will be employed to characterize uptake of HDL, processing within the endosomal compartment and trafficking to the canalicular membrane. Using an in vitro vesicle motility assay, we will explore a role for microtubules in transport and sorting of vesicles containing HDL, SR-BI and caveolin-1. Hepatocellular secretion of phosphatidylcholines into blood and bile is critical for HDL metabolism and bile formation, respectively. Phosphatidylcholine transfer protein (PC-TP) is a cytosolic lipid transfer protein of unknown function that is highly expressed in liver. Using PC-TP knockout mice, we will explore a role for this protein in reverse cholesterol transport. These studies should provide new insights into hepatic HDL metabolism and biliary lipid secretion, and may lead to early interventions in prevention and management of atherosclerosis, as well as cholesterol gallstones. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFICATION OF GENES ACTIVATED BY BILE ACIDS Principal Investigator & Institution: Edwards, Peter A.; Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Chenodeoxycholic acid (CDCA), a primary bile acid, has recently been shown to activate the farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. Recent data suggest that activated FXR controls both bile acid biosynthesis and plasma lipid levels. As such, FXR may affect the development of gallstones and/or atherosclerosis. However at the current time, very little is known about the target genes and metabolic pathways that are affected by activated FXR. In the first specific aim, we propose to use Suppression Subtractive Hybridization and DNA microarrays to identify genes that are regulated by CDCAactivated FXR. These studies will utilize HepG2 and Caco2 cells that stably overexpress high levels of FXR in order to more easily identify FXR-target genes. We will use normal, FXR-/- or VP16-FXR transgenic mice, treated with FXR ligands, to demonstrate (i) that these same genes are induced in vivo and (ii) that activation of FXR results in a decrease in plasma lipids. In the second specific aim, we will identify FXREs and other

24

Gallstones

critical cis elements in the promoters of a few selected genes that have been identified in aim 1, so as to confirm that these genes are direct targets of FXR/CDCA. In the third aim, we will generate mice that overexpress rat VP16-FXR in their livers (see aim 1). Finally, in specific aim 4, we will isolate cell lines derived from HepG2 and Caco2 cells that express either FXR1, FXR2, or FXR3. The induction of target genes, identified in aim 1, by each FXR isoform will be determined in order to test the hypothesis that specific genes/metabolic pathways are activated by each FXR isoforms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYOGENIC DISORDERS OF THE GALLBLADDER Principal Investigator & Institution: Behar, Jose; Professor of Medicine; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2001; Project Start 01-SEP-1980; Project End 30-JUN-2005 Summary: Acute cholecystitis (AC) affects 88% of patients with symptomatic gallbladder (GB) stones over a 18 year period and has a significant morbidity and mortality in elderly patients. in spite of its high prevalence, its pathogenesis has yet to be elucidated. Our preliminary studies suggest the hypothesis that human AC develops in a permissive GB environment characterized by GB stasis and impaired muscle cytoprotection that allows biliary aggressive factors to initiate the inflammatory process. This proposal therefore will study the myogenic abnormalities responsible for creating this GB environment and examine hydrophobic bile salts and reactive oxygen species (ROS) as possible aggressive factors. Specifically, it will investigate: 1) the role of bile stasis induced by lithogenic bile and excessive cholesterol (Ch) incorporation by muscle cells that seems to worsen during the inflammatory process; 2) the mechanisms of cytoprotection utilized by GB muscle cells. It will focus on the role of PGE2 in the upregulation of scavengers of free radicals and whether its receptors and pathways remain functional after exposure to soluble mediators of inflammation. It will examine the mechanisms of receptor protection and resistance to agonist induced desensitization a well as the detrimental influence of excessive membrane Ch on cytoprotective functions mediated by PGE2 receptors. Defective PGE2 receptors could make these cells more susceptible to damage by lower concentrations o aggressive factors; 3) whether hydrophobic bile salts and ROS initiate the inflammatory process and cause the muscle defects demonstrated in human and experimental AC. It will examine whether bile stasis enhances the diffusion of bile salts through the GB wall. It will also investigate the mechanisms whereby they affect muscle cells by examining whether they are mediated by ROS and whether they induce cytoprotective responses in normal and defective muscle cells; and, 4) whether hydrophobic bile salts prevent the deleterious effects of hydrophobic bile salts in vitro and whether they are effective in the prophylactic treatment of experimental AC in GB's with normal and lithogenic bile. These studies will be conducted in dissociated muscle cells from human GB's with gallstones with or without AC and from experimental AC induced by ligation of the common bile duct in animals with normal and lithogenic bile. The results of these studies may provide evidence and a rationale in support for using hydrophobic bile acids in the prophylactic treatment of this complication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURAL CONTROL OF THE GALLBLADDER Principal Investigator & Institution: Mawe, Gary M.; Professor; Anatomy and Neurobiology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405

Studies

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Timing: Fiscal Year 2001; Project Start 01-JUL-1988; Project End 28-FEB-2002 Summary: The objectives of this research program are to establish the mechanisms by which gallbladder ganglion neurons and smooth muscle cells function to promote proper filing and emptying the of the organ, and how these functions are altered in disease. Approximately 20 million people in the USA have gallstones or have had a cholecystectomy; the associated annual direct costs are comparable to the entire NIH budget. The proposed projects are designed to test hypothesis related to the cellular and subcellular mechanisms associated with disease-related hypomotility of the gallbladder, and to identify the neurotransmitters that mediate gallbladder neuromuscular transmission. The first specific aim is to determine the cellular mechanisms by which elevated cholesterol in the bile decreases gallbladder contractility. These experiments include evaluation of cholesterol's effects on ligand activation of receptors, signal transduction, channel function, and intracellular calcium mobilization. This aim will involve laser scanning confocal calcium imaging, patch clamp and intracellular recording from gallbladder neurons to test the hypotheses that cholesterol alters the ionic properties of smooth muscle and the responsiveness of gallbladder neurons and muscle cells to investigate whether opiates and somatostatin elicit biliary stasis by suppressing neuromuscular transmission in ganglia and/or at the smooth muscle. We will test the hypothesis that these compounds decrease gallbladder motility by acting presynaptically to decrease the release of excitatory transmitters in ganglia and at the neuromuscular function. The third specific aim is to identify mediators of neuromuscular transmission in the gallbladder. We use intracellular recording form muscle cells, and measurement of muscle tension, while stimulating nerves of the gallbladder to test the hypothesis that neuromuscular output from gallbladder ganglia is entirely excitatory, consisting of cholinergic and tachykinin release from local neurons onto the muscle. The proposed project will examine gallbladder function the tissue to subcellular levels, from neurons to smooth muscle, and from ensemble to single channel activity. Any array of techniques will be used, including intracellular recording, global and subcellular calcium imaging, radioimmunoassay, immunohistochemistry, and whole cell and single channel patch clamping. In this way, we hope to provide an unique, integrated view of gallbladder neuromuscular function in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OBESITY, LEPTIN AND GALLSTONE PATHOGENESIS Principal Investigator & Institution: Pitt, Henry A.; Surgery; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 15-JUL-1992; Project End 31-MAR-2006 Summary: (Verbatim from Applicant's Abstract): Approximately 30,000,000 Americans have gallstones, and the vast majority are overweight. This laboratory's long-term objective is to understand the pathogenesis of cholesterol gallstone formation. Gallstone pathogenesis is related to alterations in 1) hepatic lipid metabolism, 2) cholesterol crystal nucleation, and/or 3) biliary motility. Gallstones occur most commonly in obese, middle-aged, multiparous women. Recent studies have clarified the role of gender, iron deficiency, and female hormones in gallstone pathogenesis. Similarly, the role of leptin and malformation of its receptor in the pathogenesis of obesity has been elucidated in the last few years. However, the connections between obesity, leptin and gallstone formation remain obscure. Recent data from this laboratory is congenitally obese ob/ob mice suggest that they have alterations in biliary lipids, enhanced cholesterol crystal formation and increased gallbladder volume. Leptin receptors also have been demonstrated in the liver and biliary tree of both mice and

26

Gallstones

humans. Therefore, the hypothesis of this proposal is that leptin or malfunction of its receptor contribute to the increased incidence of gallstone formation in obesity by altering hepatic lipid metabolism, cholesterol crystal nucleation and biliary motility. Two related specific aims will be 1) to determine whether obesity, leptin, or leptin receptor malfunction alters a) hepatic lipid metabolism, b) cholesterol crystal nucleation, and/or c) biliary motility and 2) determine whether genetic alteration in leptin and its receptor on gallstone formation are additive. Preliminary studies in female, leptin deficient ob/ob mice suggest that these animals are prone to cholesterol gallstone formation. A series of studies in ob/ob, ob+/- (heterozygote), db/db (leptin receptor malfunction, and AY (Agouti yellow) mice as well genetically crossed ob/ob and db/db mice are proposed to dissect which pathogenic mechanisms link obesity, leptin and gallstones. Similarly, bile serum and tissue from lean and obese humans undergoing cholecystectomy will be systematically studied to establish clinical relevance. These studies should lead to unique strategies for gallstone prevention, which is the ultimate goal of this research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROMOTION OF PDT INDUCED PHOTOTOXICITY BY BILE ACIDS Principal Investigator & Institution: Kessel, David H.; Professor; Pharmacology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: (provided by applicant): Our studies on mechanisms of cell death after photodynamic therapy (PDT) have suggested a novel procedure for enhancing phototoxic efficacy. We had previously shown that photodynamic damage to mitochondria catalyzes release of cytochrome c into the cytosol, triggering an apoptotic response. This can bypass defective steps in the apoptotic program elicited by conventional chemotherapy. Several recent reports have indicated that the bile acid ursodeoxycholic acid (UDCA) could protect the mitochondrial membrane of hepatoma cells from the pro-apoptotic effects of several agents including ethanol, deoxycholic acid, hydrogen peroxide and cadmium ion. We expected that UDCA would also protect mitochondria, an important PDT target, from the induction of an apoptotic response after PDT. We found instead the opposite effect: a significant promotion of cytochrome c release, caspase-3 activation and apoptotic cell death. This was demonstrated in both murine leukemia and hepatoma lclc7 cells. In the former cell line, we also demonstrated that UDCA could promote the apoptotic response to photosensitizing agents that catalyze selective photodamage to the anti-apoptotic protein Bcl-2, but do not affect the pro-apoptotic protein Bax. In a pilot study, we found the lifespan of mice bearing the RIF tumor was enhanced when UDCA was administered before irradiation, using the tin etiopurpurin SnET2 as the photosensitizing agent. These results are of potentially great clinical significance since UDCA is widely used for the treatment of gallstones and liver diseases, and its pharmacology and safety have been well established. To provide information on the pertinent mechanisms, we plan to [1] characterize the effects of UDCA on the cytotoxic responses to a spectrum of photosensitizing agents, [2] assess the structure-activity relationships in a series of UDCA analogs including the glycineand taurine-conjugates that are formed in vivo, [3] examine the efficacy of UDCA for PDT enhancement in a variety of tumor cell lines, [4] measure PDT-promotion by UDCA and selected analogs in animal tumor models. Our hypothesis is that UDCA partitions into mitochondrial membranes and both lowers the threshold of photodamage, while offering protection from the chaotropic effects of more hydrophobic bile acids. Aim [4] will be carried out in a sub-contract with the PDT

Studies

27

facility at University of Louisville where there is the required expertise in animal PDT studies. If the results of preliminary studies are borne out by further investigation, UDCA could offer a safe and effective means for promoting clinical PDT efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEIN LIPID INTERACTIONS IN GALLSTONE PATHOGENESIS Principal Investigator & Institution: Afdhal, Nezam H.; Associate Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 15-JUL-1993; Project End 31-MAY-2003 Summary: Cholesterol gallstone disease is one of the commonest digestive diseases in the United States and results in 700,000 cholecystectomies annually with a direct health care cost in excess of $3 billion. Gallbladder mucin plays a central role in gallstone formation and this proposal will examine the mechanism by which mucin interacts with biliary lipids to promote gallstones. The specific Aims are to 1) Characterize the interaction of specific sites of the mucin molecule with lipid vesicles to improve our understanding of how mucin promotes crystallization of cholesterol monohydrate; 2) Characterize how mucin effects the morphology and rate of crystal growth in solution and in gels so that growth inhibitors can eventually be developed; 3) Examine the central role of mucin as the matrix protein in the biomineralization of both calcium and cholesterol. These Aim's will be achieved by utilizing multiple biophysical techniques to examine model systems where mucin and its modified structural forms will interact with biliary lipids similar to those seen in gallstone bile. Fluorescent assays, dynamic light scattering and magic angle spinning magnetic resonance will examine how mucin promotes vesicle fusion and sub- microscopic nucleation. Light and electron microscopy will examine the way in which mucin can promote both the pattern and rate of crystal growth. These studies may lead to strategies for the prevention and non-surgical therapy of this very common disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF ABCG5 AND ABCG8 IN STEROL METABOLISM Principal Investigator & Institution: Hobbs, Helen H.; Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The dysregulation of sterol metabolism is a critical factor in the development of two major human diseases: coronary atherosclerosis, the leading cause of death in the Western societies, and cholesterol gallstones, one of the leading indicators for surgery in the United States. The basic pathways of sterol transport in the body have been well defined: sterols enter the body via endogenous synthesis and intestinal absorption and are excreted via the liver into the bile, either as the free sterol or after conversion to bile acids. The two major organ systems involved in these processes, the liver and intestine, provide critical barriers to the accumulation of sterols in the body, but the molecular constituents and mechanisms of action of these barriers are poorly understood. A major unresolved issue that remains to be addressed is whether specific cell membrane transporters facilitate the translocation of cholesterol across the intestinal and bile canalicular membranes. An important clue to the molecular mechanisms that defend against sterol accumulation has recently emerged from studies of sitosterolemia, a genetic disorder associated with increased sterol absorption and decreased sterol excretion. Recently, we showed that sitosterolemia is due to mutations in two ATP-binding cassette (ABC) proteins, ABCG5 and ABCG8. The profound

28

Gallstones

alteration in sterol homeostasis observed in sitosterolemic patients indicates that ABCG5 and ABCG8 serve to limit sterol absorption in the intestine and promote sterol excretion in the bile, but almost nothing is known about the basic function and characteristics of these two proteins. The overall goal of this grant proposal is to elucidate the basic mechanisms by which ABCG5 and ABCG8 limit sterol absorption in the intestine and facilitate sterol excretion in hepatocytes. The studies proposed are designed to address three critical questions: First, where are ABCG5 and ABCG8 located in the cell? Second, what is the functional form of ABCG5 and ABCG8? Third, what substrate(s) do ABCG5 and ABCG8 transport? To address these questions, we propose a comprehensive series of biochemical studies that will allow a direct and quantitative investigation of the ABCG5/8 transport system. The subcellular location of ABCG5 and ABCG8 will be determined by microscopy and cell fractionation. The functional form of ABCG5 and ABCG8 will be determined by co-immunoprecipitation studies to identify the primary dimerization partners, and then by purification of the native proteins to identify other components of the transport complex. Finally, a functional transport complex will be reconstituted in proteoliposomes to define the substrate and basic enzymatic properties of the transporter. These studies will provide a comprehensive understanding of the molecular mechanisms of this important transport system that protects against hypercholesterolemia and coronary atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF GALLBLADDER ION TRANSPORT IN GALLSTONE FORMATION Principal Investigator & Institution: Moser, a J.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant) The candidate is an academic gastrointestinal surgeon whose career objective is to become an independently funded clinician scientist. After graduating at the top of his class from college and medical school, the candidate trained in surgery at UCLA. He undertook a Research Fellowship during residency that provided preliminary experience in membrane biology and instilled a strong desire to become a clinician scientist and an innovator in the treatment of gallstones. To develop his research career, the candidate needs significantly more time for scientific pursuits as well as the mentorship of an experienced membrane biologist. His career development plan includes both didactic and practical studies of gallbladder ion transport with the supervision of two highly successful and innovative scientists at the University of Pittsburgh. The environment provided by the Laboratory of Epithelial Cell Biology is outstanding and has already trained numerous accomplished clinician scientists. The sponsors have dedicated their laboratory resources, equipment, and time to insure the candidate's success. The research plan focuses on one therapeutically promising aspect of gallstone pathogenesis: increased salt and water absorption by the gallbladder prior to gallstone formation. Increased electrolyte absorption excessively concentrates gallbladder bile and promotes the crystallization of cholesterol. The potential clinical relevance of increased gallbladder salt and water transport is dramatized by data showing that amiloride prevents the formation of gallstones in cholesterol-fed prairie dogs. Contrary to the paradigm for gallbladder transport described in stone-resistant animals, we now demonstrate electrogenic ion transport in human and prairie dog gallbladder. Alterations in electrogenic ion transport precede the formation of gallstones and cause absorption to increase, and the mechanism is unknown. We propose studies with three Specific Aims to test our hypothesis that electrogenic ion

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transport confers susceptibility to the formation of gallstones; Aim 1: Determine the mechanism for electrogenic ion transport in prairie dog gallbladder. Although prairie dogs are used extensively as a model of human disease, the basic mechanism for gallbladder ion transport in normal prairie dogs has not been established. Aim 2: Characterize alterations in gallbladder ion transport prior to the formation of gallstones. Using cholesterol-fed animals, we will test our hypothesis that alterations in channelmediated ion transport stimulate electrolyte absorption and promote gallstones. Aim 3: Determine the mechanism for human gallbladder ion transport in health and disease. Given the high incidence of gallstones in patients with abnormal gallbladder ion transport, these studies will test our hypothesis that increased gallbladder electrolyte absorption is also a cause of gallstones in man. These studies are ideal for teaching the Principal Investigator critical new skills required for a successful research career as a clinician scientist in an era of increasingly sophisticated membrane biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECOND MESSENGERS, GALLBLADDER ABSORPTION AND GALLSTONES Principal Investigator & Institution: Abedin, Mohammad Z.; Surgery; Mcp Hahnemann University Broad & Vine Sts Philadelphia, Pa 19102 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: (Adapted from investigator's abstract) The development of cholesterol gallstones involves alterations in the relationship of the amount of cholesterol, phospholipid and bile salts present in bile resulting in bile becoming supersaturated with cholesterol. Cholesterol crystal formation then occurs and aggregation of crystals results in macro stone formation. During the crystalline and early stages of gallstone formation increased absorption of sodium and water occurs which is believed to contribute to the formation of stones by potentially increasing the concentration of crystals and nucleating factors. The proposed research is directed at determining the mechanisms by which supersaturated bile increase gallbladder absorption. The absorption of water is dependent on the transport of sodium which is dependent on the function of various Na+/H+ exchangers. The activity of the Na/HE is regulated by a number of factors which possibly include cyclic nucleotides and calcium. The proposed research intends to determine if lithogenic bile increases gallbladder absorption and the activity of the second messenger system and if these alterations are necessary for gallstone formation. The research will determine the mechanisms of sodium absorption, if it is regulated by the cyclic AMP/ Ca++ second messenger system and if these alterations accompany cholesterol gallstone formation in the cholesterol fed prairie dog. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF NITRIC OXIDE IN CHOLESTEROL HOMEOSTASIS Principal Investigator & Institution: Ihrig, Melanie M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Cholesterol homeostasis is maintained by balancing intestinal absorption, endogenous biosynthesis, hepatic uptake and biliary secretion of cholesterol and bile acids. Recently, there has been a renewed interest in the role of intestinal cholesterol absorption in cholesterol homeostasis. A number of studies have assessed the effect of reduced small bowel transit time on cholesterol absorption, and each found a significant correlation between transit time, cholesterol absorption and

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Gallstones

serum cholesterol concentration. We have demonstrated that mice with a targeted mutation in the inducible nitric oxide synthase (iNOS) gene have elevated serum cholesterol levels. Each of three unique isoforms of NOS is expressed in different cell types and under different conditions throughout the gastrointestinal tract. There is considerable evidence that nitric oxide (NO) produced in the gastrointestinal tract influences enteric myoelectrical activity, coordinates peristalsis and ultimately affects intestinal transit time. Nitric oxide acts as an inhibitory neurotransmitter, and as a vasodilator in the intestinal tract. Additionally, enteric pathogens, and the experimental administration of lipopolysaccharide (LPS), elicit excessive production of NO through transcriptional upregulation of iNOS. Thus, NO concentrations in the intestinal tract wax and wane depending on the immediate circumstances. A plausible explanation for the increased serum cholesterol levels observed in the iNOS-deficient mice, then, is delayed small bowel transit time, brought on by perturbation of the regulation and coordination of intestinal motility. Aberrant cholesterol homeostasis is a risk factor for both atherosclerosis and cholesterol gallstone formation. In addition to hypercholesterolemia, we observed aortic atheromas in the iNOS-deficient mice. Prolonged intestinal transit time augments formation of cholesterol gallstones, and if prolonged intestinal transit time is the underlying cause of hypercholesterolemia in iNOS-deficient mice, the manifestation of atherosclerosis and cholelithiasis may well be linked. The proposed studies will explore these possibilities in iNOS-deficient mice under various experimental conditions. 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 “gallstones” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for gallstones in the PubMed Central database: •

A comparative study of gallstones from children and adults using FTIR spectroscopy and fluorescence microscopy. by Kleiner O, Ramesh J, Huleihel M, Cohen B, Kantarovich K, Levi C, Polyak B, Marks RS, Mordehai J, Cohen Z, Mordechai S.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65695

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Biofilm Formation and Interaction with the Surfaces of Gallstones by Salmonella spp. by Prouty AM, Schwesinger WH, Gunn JS.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127943

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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Bouveret's syndrome complicated by distal gallstone ileus after laser lithotropsy using Holmium: YAG laser. by Alsolaiman MM, Reitz C, Nawras AT, Rodgers JB, Maliakkal BJ.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117132

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Lith1, a Major Gene Affecting Cholesterol Gallstone Formation Among Inbred Strains of Mice. by Khanuja B, Cheah Y, Hunt M, Nishina PM, Wang DQ, Chen HW, Billheimer JT, Carey MC, Paigen B.; 1995 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41219

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

A comparative study of gallstones from children and adults using FTIR spectroscopy and fluorescence microscopy. Author(s): Kleiner O, Ramesh J, Huleihel M, Cohen B, Kantarovich K, Levi C, Polyak B, Marks RS, Mordehai J, Cohen Z, Mordechai S. Source: Bmc Gastroenterology [electronic Resource]. 2002; 2(1): 3. Epub 2002 February 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872150&dopt=Abstract

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A rational approach to cholelithiasis in bariatric surgery: its application to the laparoscopically placed adjustable gastric band. Author(s): O'Brien PE, Dixon JB. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 August; 138(8): 908-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912752&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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Abdominal wall abscess secondary to spilled gallstones: late complication of laparoscopic cholecystectomy and preventive measures. Author(s): Yao CC, Wong HH, Yang CC, Lin CS. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2001 February; 11(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444325&dopt=Abstract

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Age-related changes in the chemical composition of gallstones. Author(s): Kurtin WE, Schwesinger WH, Diehl AK. Source: International Journal of Surgical Investigation. 2000; 2(4): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678532&dopt=Abstract

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Application of focused-microwave wet digestion to the determination of trace metals in human gallstones by ICP/AES. Author(s): Sahuquillo A, Rubio R, Ribo JM, Ros E, Vela M. Source: Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (Gms). 2000 June; 14(2): 96-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10941721&dopt=Abstract

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Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer and prevents the formation of cholesterol gallstones in inbred mice. Author(s): Gilat T, Leikin-Frenkel A, Goldiner L, Laufer H, Halpern Z, Konikoff FM. Source: Lipids. 2001 October; 36(10): 1135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768158&dopt=Abstract

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Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Author(s): Serra I, Yamamoto M, Calvo A, Cavada G, Baez S, Endoh K, Watanabe H, Tajima K. Source: International Journal of Cancer. Journal International Du Cancer. 2002 December 1; 102(4): 407-11. Erratum In: Int J Cancer. 2003 May 10; 104(6): 798. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402311&dopt=Abstract

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Association of obesity and type II diabetes mellitus as a risk factor for gallstones. Author(s): Pacchioni M, Nicoletti C, Caminiti M, Calori G, Curci V, Camisasca R, Pontiroli AE. Source: Digestive Diseases and Sciences. 2000 October; 45(10): 2002-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117574&dopt=Abstract

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Asymptomatic gallstones and duration of cyclosporine use in kidney transplant recipients. Author(s): Alberu J, Gatica M, Cachafeiro-Vilar M, Robles-Diaz G, Bezaury P, PazPinedo F, Vargas-Vorackova F. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2001 September-October; 53(5): 396-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795104&dopt=Abstract

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Asymptomatic gallstones in the laparoscopic era. Author(s): Meshikhes AW. Source: Journal of the Royal College of Surgeons of Edinburgh. 2002 December; 47(6): 742-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510966&dopt=Abstract

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Atypical gastrointestinal symptoms are not associated with gallstones in patients with spinal cord injury. Author(s): Moonka R, Stiens SA, Stelzner M. Source: Archives of Physical Medicine and Rehabilitation. 2000 August; 81(8): 1085-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943760&dopt=Abstract

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Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones. Author(s): Gustafsson U, Sahlin S, Einarsson C. Source: European Journal of Clinical Investigation. 2000 December; 30(12): 1099-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122325&dopt=Abstract

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Biofilm formation and interaction with the surfaces of gallstones by Salmonella spp. Author(s): Prouty AM, Schwesinger WH, Gunn JS. Source: Infection and Immunity. 2002 May; 70(5): 2640-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953406&dopt=Abstract

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By the way, doctor. I recently had an ultrasound to look for gallstones. No gallstones. But they found an abdominal aortic aneurysm instead. The doctors said it's pretty small--only 3.8 centimeters. But I'm worried that it might get larger and break open. Is there anything I can do to prevent it from getting bigger? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2003 February; 28(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604457&dopt=Abstract

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Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones. Author(s): Tazuma S, Kajiyama G. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2001 April; 386(3): 224-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382326&dopt=Abstract

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Case records of the VA Maryland Healthcare System/University of Maryland Medicine. A 75-year-old man with right upper quadrant pain and gallstones. Author(s): Oursler KA, Saladino AJ. Source: The American Journal of the Medical Sciences. 2002 March; 323(3): 146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908859&dopt=Abstract

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Cholecystitis, gallstones and free radical reactions in human gallbladder. Author(s): Sipos P, Krisztina H, Blazovics A, Feher J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 January-February; 7(1): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208499&dopt=Abstract

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Cholesterol gallstones: from epidemiology to prevention. Author(s): Acalovschi M. Source: Postgraduate Medical Journal. 2001 April; 77(906): 221-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264482&dopt=Abstract

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Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones. Author(s): Dhiman RK, Reddi R, Sharma A, Singh R, Kohli KK, Gupta S, Suri S, Chawla Y. Source: Journal of Gastroenterology and Hepatology. 2001 July; 16(7): 816-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446892&dopt=Abstract

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Classification and nomenclature of gallstones revisited. Author(s): Kim IS, Myung SJ, Lee SS, Lee SK, Kim MH. Source: Yonsei Medical Journal. 2003 August 30; 44(4): 561-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950109&dopt=Abstract

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Clinics in diagnostic imaging (62). Gallstones with acute cholecystitis. Author(s): Muttarak M, Na Chiangmai W. Source: Singapore Med J. 2001 June; 42(6): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547969&dopt=Abstract

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Complications due to gallstones lost during laparoscopic cholecystectomy. Author(s): Brockmann JG, Kocher T, Senninger NJ, Schurmann GM. Source: Surgical Endoscopy. 2002 August; 16(8): 1226-32. Epub 2002 May 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984670&dopt=Abstract

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Composition and immunofluorescence studies of biliary “sludge” in patients with cholesterol or mixed gallstones. Author(s): de la Porte PL, Lafont H, Domingo N, Meyer G, Muller I, Zundt B, Jungst D. Source: Journal of Hepatology. 2000 September; 33(3): 352-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11019989&dopt=Abstract

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Composition of gallstones and sequential events in biliary lithogenesis--is it different in south India compared to north? Author(s): Amin AM, Ananthakrishnan N, Nambinarayanan TK. Source: J Assoc Physicians India. 2000 September; 48(9): 885-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198787&dopt=Abstract

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Concomitant laparoscopic splenectomy and cholecystectomy as an effective and minimally invasive treatment of pyruvate kinase deficiency with gallstones. Author(s): Watanabe Y, Miyauchi K, Horiuchi A, Kikkawa H, Kusunose H, Kotani T, Kawachi K. Source: Surgical Endoscopy. 2002 October; 16(10): 1495. Epub 2002 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089633&dopt=Abstract

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Concomitant laparoscopic splenectomy and cholecystectomy for management of hereditary spherocytosis associated with gallstones. Author(s): Yamagishi S, Watanabe T. Source: Journal of Clinical Gastroenterology. 2000 June; 30(4): 447. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875481&dopt=Abstract

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Development of black gallstones after the nonsurgical management of splenic injury: report of a case. Author(s): Hase T, Kodama M, Hanazawa K, Kurumi Y, Domasu S, Fujita M, Nakamura K, Morita K, Nakamura K. Source: Surgery Today. 1997; 27(10): 958-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870584&dopt=Abstract

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DNA ploidy and S-phase fraction in carcinoma of the gallbladder related to histopathology, number of gallstones and survival. Author(s): Gustafsson U, Einarsson C, Eriksson LC, Gadaleanu V, Sahlin S, Tribukait B. Source: Analytical Cellular Pathology : the Journal of the European Society for Analytical Cellular Pathology. 2001; 23(3-4): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12082295&dopt=Abstract

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Does prophylactic endoscopic sphincterotomy prevent recurrent biliary problems in patients with gallstones and a normal cholangiogram? Author(s): Johnston SD, Lim P, Collins JS, Watson RG, Tham TC. Source: Ir J Med Sci. 2002 October-December; 171(4): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647907&dopt=Abstract

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Does spinal manipulation really cure gallstones? Alternative medicine and the general surgeon. Author(s): Zannis VJ. Source: American Journal of Surgery. 2000 December; 180(6): 389-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182384&dopt=Abstract

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Dropped gallstones post laparoscopic cholecystectomy mimicking peritoneal seeding: CT and ultrasound features. Author(s): Atri M, Bonifacio A, Ryan M, Pilleul FL, Hanbidge A, Clark J, Murphy J. Source: Journal of Computer Assisted Tomography. 2002 November-December; 26(6): 1000-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488750&dopt=Abstract

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Dying of gallstones. Author(s): Weinger MB, Dunn EJ, Cohn F. Source: The Hastings Center Report. 2003 January-February; 33(1): 14; Discussion 15-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613382&dopt=Abstract

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Effect of cholecystectomy for gallstones on the surface of the papilla of Vater and the diameter of the common bile duct. Author(s): Skalicky M, Dajcman D, Hojs R. Source: European Journal of Gastroenterology & Hepatology. 2002 April; 14(4): 399-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943953&dopt=Abstract

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Effect of dietary consumption, advanced age and overweight on the physical characteristics of cholesterol gallstones and biliary lipid composition in west Algerian women. Author(s): Lamri-Senhadji MY, Mekki K, El Kebir B, Bachir-Bouiadjra N, Bouchenak M, Belleville J. Source: Annals of Nutrition & Metabolism. 2002; 46(3-4): 139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169857&dopt=Abstract

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Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones. Author(s): Smith JL, Roach PD, Wittenberg LN, Riottot M, Pillay SP, Nestel PJ, Nathanson LK. Source: Journal of Gastroenterology and Hepatology. 2000 August; 15(8): 871-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022827&dopt=Abstract

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Endoscopic diagnosis and management of complications following surgery for gallstones. Author(s): Yamaner S, Bilsel Y, Bulut T, Bugra D, Buyukuncu Y, Akyuz A, Sokucu N. Source: Surgical Endoscopy. 2002 December; 16(12): 1685-90. Epub 2002 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140632&dopt=Abstract

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Endoscopic sonography in the diagnosis of gallbladder wall lesions in patients with gallstones. Author(s): Muguruma N, Okamura S, Ichikawa S, Tsujigami K, Suzuki M, Tadatsu M, Kusaka Y, Okita Y, Yano M, Ito S. Source: Journal of Clinical Ultrasound : Jcu. 2001 September; 29(7): 395-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579402&dopt=Abstract

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Enterohepatic cycling of bilirubin as a cause of 'black' pigment gallstones in adult life. Author(s): Vitek L, Carey MC. Source: European Journal of Clinical Investigation. 2003 September; 33(9): 799-810. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925040&dopt=Abstract

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Epidemiological correlation between chromium content in gallstones and cholesterol in blood. Author(s): Shigeta A, Ratanamaneechat S, Srisukho S, Tanaka M, Moriyama Y, Suwanagool S, Miki M. Source: J Med Assoc Thai. 2002 February; 85(2): 183-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081118&dopt=Abstract

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Evaluation of garlic oil as a contact dissolution agent for gallstones: comparison with monooctanoin. Author(s): Nijhawan S, Agarwal V, Sharma D, Rai RR. Source: Trop Gastroenterol. 2000 October-December; 21(4): 177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194578&dopt=Abstract

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Extracorporeal shock wave lithotripsy of gallstones with oral dissolution. Results in course of ten years in Czech Republic in correlation to indication criteria. Author(s): Benes J, Chmel J, Blazek O, Marecek Z. Source: Sb Lek. 2001; 102(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830914&dopt=Abstract

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Extraction of retained gallstones from an abscess cavity: a percutaneous endoscopic technique. Author(s): Kelkar AP, Kocher HM, Makar AA, Patel AG. Source: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. 2001 April; 11(2): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11330379&dopt=Abstract

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Factors influencing the prevalence of gallstones in liver disease: the beneficial and harmful influences of alcohol. Author(s): Buchner AM, Sonnenberg A. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 905-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003426&dopt=Abstract

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Gallbladder carcinoma associated with gallstones. Author(s): Gurleyik G, Gurleyik E, Ozturk A, Unalmiser S. Source: Acta Chir Belg. 2002 June; 102(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136543&dopt=Abstract

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Gallstones and biliary disease. Author(s): Kalloo AN, Kantsevoy SV. Source: Primary Care. 2001 September; 28(3): 591-606, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483446&dopt=Abstract

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Gallstones and cholecystectomy in modern Britain. Author(s): Bateson MC. Source: Postgraduate Medical Journal. 2000 November; 76(901): 700-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060144&dopt=Abstract

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Gallstones and ethnicity in the Americas. Author(s): Everhart JE. Source: J Assoc Acad Minor Phys. 2001 July; 12(3): 137-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858192&dopt=Abstract

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Gallstones and gall bladder carcinoma. Author(s): Vitetta L, Sali A, Little P, Mrazek L. Source: The Australian and New Zealand Journal of Surgery. 2000 September; 70(9): 66773. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976897&dopt=Abstract

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Gallstones and laparoscopic cholecystectomy in hepatitis C patients. Author(s): O'Sullivan MJ, Evoy D, O'Donnell C, Rajpal PK, Cannon B, Kenny-Walsh L, Whelton MJ, Redmond HP, Kirwan WO. Source: Ir Med J. 2001 April; 94(4): 114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440047&dopt=Abstract

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Gallstones in elderly patients: impact of laparoscopic cholecystectomy. Author(s): Montori A, Boscaini M, Gasparrini M, Miscusi G, Masoni L, Onorato M, Montori J. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 December; 14(11): 929-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11125183&dopt=Abstract

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Gallstones in males. Author(s): Dunn JP. Source: N Z Med J. 2000 April 28; 113(1108): 152-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10872440&dopt=Abstract

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Gallstones in obesity and weight loss. Author(s): Erlinger S. Source: European Journal of Gastroenterology & Hepatology. 2000 December; 12(12): 1347-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192327&dopt=Abstract

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Gallstones in portal hypertension: is the liver or the portal hypertension responsible? Author(s): Abraham P, Desai DC, Joshi AG. Source: J Assoc Physicians India. 2002 April; 50: 515-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164400&dopt=Abstract

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Gallstones in spinal cord injury (SCI): a late medical complication? Author(s): Rotter KP, Larrain CG. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 2003 February; 41(2): 105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595873&dopt=Abstract

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Gallstones in the elderly. Author(s): Pauletzki J. Source: European Journal of Gastroenterology & Hepatology. 1999 May; 11(5): 473-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755247&dopt=Abstract

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Gallstones, cholecystectomy, and the risk for developing pancreatic cancer. Author(s): Schernhammer ES, Michaud DS, Leitzmann MF, Giovannucci E, Colditz GA, Fuchs CS. Source: British Journal of Cancer. 2002 April 8; 86(7): 1081-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953853&dopt=Abstract

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Gallstones, from gallbladder to gut. Management options for diverse complications. Author(s): Agrawal S, Jonnalagadda S. Source: Postgraduate Medicine. 2000 September 1; 108(3): 143-6, 149-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004941&dopt=Abstract

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Gallstones, gallbladder disease, and pancreatitis: cross-sectional and 2-year data from the Swedish Obese Subjects (SOS) and SOS reference studies. Author(s): Torgerson JS, Lindroos AK, Naslund I, Peltonen M. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1032-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809825&dopt=Abstract

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Gallstones, the choledochoduodenal junction and initiation of acute pancreatitis: are two stones the culprits rather than one stone? Author(s): Arendt T, Monig H, Stuber E, Katsoulis S, Folsch UR. Source: Medical Hypotheses. 2000 April; 54(4): 570-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10859640&dopt=Abstract

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Gallstones. Modern management. Author(s): Fletcher DR. Source: Aust Fam Physician. 2001 May; 30(5): 441-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11432016&dopt=Abstract

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Gallstones: genetics versus environment. Author(s): Nakeeb A, Comuzzie AG, Martin L, Sonnenberg GE, Swartz-Basile D, Kissebah AH, Pitt HA. Source: Annals of Surgery. 2002 June; 235(6): 842-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12035041&dopt=Abstract

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Gallstones: prevalence, diagnosis and treatment. Author(s): Bar-Meir S. Source: Isr Med Assoc J. 2001 February; 3(2): 111-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344819&dopt=Abstract

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Gallstones--an increasing problem: a study of hospital admissions in England between 1989/1990 and 1999/2000. Author(s): Kang JY, Ellis C, Majeed A, Hoare J, Tinto A, Williamson RC, Tibbs CJ, Maxwell JD. Source: Alimentary Pharmacology & Therapeutics. 2003 February 15; 17(4): 561-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622765&dopt=Abstract

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Genetic determinants of jaundice and gallstones in haemoglobin E beta thalassaemia. Author(s): Premawardhena A, Fisher CA, Fathiu F, de Silva S, Perera W, Peto TE, Olivieri NF, Weatherall DJ. Source: Lancet. 2001 June 16; 357(9272): 1945-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425418&dopt=Abstract

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HDL receptor SR-BI and cholesterol gallstones. Author(s): Rigotti A, Zanlungo S, Miquel JF, Wang DQ. Source: Hepatology (Baltimore, Md.). 2002 January; 35(1): 240-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786985&dopt=Abstract

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Hepatic Schistosomiasis japonica in a patient with gallstones and bile duct stones--a case report. Author(s): Lin JN, Yen CM, Liu CS, Tsai MS, Kuo KK. Source: Kaohsiung J Med Sci. 2001 August; 17(8): 437-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11715844&dopt=Abstract

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Histologic findings of gallbladder mucosa in 87 patients with morbid obesity without gallstones compared to 87 control subjects. Author(s): Csendes A, Burdiles P, Smok G, Csendes P, Burgos A, Recio M. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 May-June; 7(4): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763414&dopt=Abstract

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Histopathological changes in gallbladder mucosa in cholelithiasis: correlation with chemical composition of gallstones. Author(s): Baig SJ, Biswas S, Das S, Basu K, Chattopadhyay G. Source: Trop Gastroenterol. 2002 January-March; 23(1): 25-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170916&dopt=Abstract

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Holmium: YAG laser lithotripsy for gallstones. A preliminary report. Author(s): Teichman JM, Schwesinger WH, Lackner J, Cossman RM. Source: Surgical Endoscopy. 2001 September; 15(9): 1034-7. Epub 2001 July 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605114&dopt=Abstract

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Human biliary beta-glucuronidase activity before and after relief of bile duct obstruction: is it the major role in the formation of pigment gallstones? Author(s): Chen CY, Shiesh SC, Tsao HC, Lin XZ. Source: Journal of Gastroenterology and Hepatology. 2000 September; 15(9): 1071-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059940&dopt=Abstract

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Identification of Helicobacter pylori DNA in human cholesterol gallstones. Author(s): Monstein HJ, Jonsson Y, Zdolsek J, Svanvik J. Source: Scandinavian Journal of Gastroenterology. 2002 January; 37(1): 112-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843027&dopt=Abstract

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Identification of oxysterols in human bile and pigment gallstones. Author(s): Haigh WG, Lee SP. Source: Gastroenterology. 2001 July; 121(1): 118-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438500&dopt=Abstract

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Images in medicine. “Dropped” gallstones. Author(s): Geist M. Source: Medicine and Health, Rhode Island. 2002 March; 85(3): 103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917743&dopt=Abstract

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Images of interest. Hepatobiliary and pancreatic: an old woman with gallstones. Author(s): Okuda K, Tsuchiya Y, Sugiura N. Source: Journal of Gastroenterology and Hepatology. 2001 February; 16(2): 225; Discussion 228-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207906&dopt=Abstract

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In vitro dissolution of cholesterol and brown pigmented gallstones: a comparison of MTBE, DMSO and BA-EDTA. Author(s): Cheng JS, Lai KH, Lo GH, Ng WW, Tam TN, Huang SM. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 September; 63(9): 667-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037641&dopt=Abstract

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Incarcerated indirect inguinal hernia: a complication of spilled gallstones. Author(s): Bebawi M, Wassef S, Ramcharan A, Bapat K. Source: Jsls. 2000 July-September; 4(3): 267-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987409&dopt=Abstract

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Incidence of gallstones in chronic renal failure patients undergoing hemodialysis: experience of a center in Turkey. Author(s): Altiparmak MR, Pamuk ON, Pamuk GE, Celik AF, Apaydin S, Cebi D, Mihmanli I, Erek E. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 813-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738461&dopt=Abstract

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Increased frequency of gallstones in cirrhotic and non-cirrhotic portal hypertension. Author(s): Sarin SK, Guptan RC, Malhotra S. Source: J Assoc Physicians India. 2002 April; 50: 518-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164401&dopt=Abstract

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Influence of cholecystitis state on pharmacological response to cholecystokinin of isolated human gallbladder with gallstones. Author(s): Martinez-Cuesta MA, Moreno L, Morillas J, Ponce J, Esplugues JV. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 898-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772786&dopt=Abstract

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Influence of laparoscopic cholecystectomy on the prevalence of operations for gallstones in Norway. Author(s): Pedersen G, Hoem D, Andren-Sandberg A. Source: The European Journal of Surgery = Acta Chirurgica. 2002; 168(8-9): 464-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549686&dopt=Abstract

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Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey. Author(s): Cimino L, Oriani G, D'Arienzo A, Manguso F, Loguercio C, Ascione A, Caporaso N, Del Vecchio Blanco C, Budillon G. Source: Dig Liver Dis. 2001 April; 33(3): 240-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407669&dopt=Abstract

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Internet based expert system for the management of gallstones, renal, ureteric and bladder calculi. Author(s): Sridhar S, Kumaravel N. Source: Biomed Sci Instrum. 2003; 39: 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724865&dopt=Abstract

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Intestinal motility and bacterial overgrowth in patients with gallstones. Author(s): Mendez-Sanchez N, Uribe M. Source: Gastroenterology. 2001 April; 120(5): 1310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288749&dopt=Abstract

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Is the loss of gallstones during laparoscopic cholecystectomy an underestimated complication? Author(s): Gerlinzani S, Tos M, Gornati R, Molteni B, Poliziani D, Taschieri AM. Source: Surgical Endoscopy. 2000 April; 14(4): 373-4. Epub 2000 February 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854525&dopt=Abstract

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Laparoscopic cholecystectomy for symptomatic gallstones in diabetic patients. Author(s): Bedirli A, Sozuer EM, Yuksel O, Yilmaz Z. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2001 October; 11(5): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642663&dopt=Abstract

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Laparoscopic cholecystectomy for symptoms of biliary colic in the absence of gallstones. Author(s): Brosseuk D, Demetrick J. Source: American Journal of Surgery. 2003 July; 186(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842737&dopt=Abstract

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Laparoscopic cholecystectomy to treat patients with asymptomatic gallstones. Author(s): Coelho JC, Vizzoto AO, Salvalaggio PR, Tolazzi AR. Source: Digestive Surgery. 2000; 17(4): 344-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053940&dopt=Abstract

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Long-term evaluation of extracorporeal shock-wave lithotripsy for cholesterol gallstones. Author(s): Tsumita R, Sugiura N, Abe A, Ebara M, Saisho H, Tsuchiya Y. Source: Journal of Gastroenterology and Hepatology. 2001 January; 16(1): 93-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11206322&dopt=Abstract

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Management of patients with gallstones and ductal calculi. Author(s): Cuschieri A. Source: Lancet. 2002 September 7; 360(9335): 739-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241828&dopt=Abstract

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Managing gallstones. Author(s): Bateson MC. Source: The Practitioner. 2001 August; 245(1625): 659-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524937&dopt=Abstract

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Massive hemoptysis from a lung abscess due to retained gallstones. Author(s): Werber YB, Wright CD. Source: The Annals of Thoracic Surgery. 2001 July; 72(1): 278-9; Discussion 280. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465203&dopt=Abstract

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Modern concepts in the management of biliary stones (gallstones). Author(s): Bhattacharyya M. Source: J Indian Med Assoc. 2001 June; 99(6): 325-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678621&dopt=Abstract

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Morphological and demographic associations of biliary symptoms in subjects with gallstones: findings from a population-based survey in Rosario, Argentina. Author(s): Brasca A, Berli D, Pezzotto SM, Gianguzza MP, Villavicencio R, Fray O, Poletto L. Source: Dig Liver Dis. 2002 August; 34(8): 577-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502214&dopt=Abstract

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MR cholangiography in symptomatic gallstones: diagnostic accuracy according to clinical risk group. Author(s): Kim JH, Kim MJ, Park SI, Chung JJ, Song SY, Kim KS, Yoo HS, Lee JT, Kim KW. Source: Radiology. 2002 August; 224(2): 410-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147836&dopt=Abstract

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Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones. Author(s): Jungst D, Niemeyer A, Muller I, Zundt B, Meyer G, Wilhelmi M, del Pozo R. Source: World Journal of Gastroenterology : Wjg. 2001 April; 7(2): 203-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11819761&dopt=Abstract

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No association between gallstones and gastroesophageal reflux disease. Author(s): Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Source: The American Journal of Gastroenterology. 2001 October; 96(10): 2858-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693317&dopt=Abstract

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Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma. Author(s): Serra I, Diehl AK. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 March-April; 6(2): 272-3; Author Reply 273. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992815&dopt=Abstract

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Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: a prospective study of 592 cases. Author(s): Csendes A, Becerra M, Rojas J, Medina E. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2000 September-October; 4(5): 481-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077323&dopt=Abstract

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Pathogenesis of pigment gallstones in Western societies: the central role of bacteria. Author(s): Stewart L, Oesterle AL, Erdan I, Griffiss JM, Way LW. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 November-December; 6(6): 891-903; Discussion 903-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504229&dopt=Abstract

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Percutaneous removal of spilled gallstones in a subhepatic abscess. Author(s): Albrecht RM, Eghtestad B, Gibel L, Locken J, Champlin A. Source: The American Surgeon. 2002 February; 68(2): 193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842969&dopt=Abstract

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Pericholecystic adhesions in single v multiple gallstones and their consequences for laparoscopic cholecystectomy. Author(s): Verma GR, Bose SM, Wig JD. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2001 October; 11(5): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642662&dopt=Abstract

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Physical activity, biliary lipids, and gallstones in obese subjects. Author(s): Chuang CZ, Martin LF, LeGardeur BY, Lopez A. Source: The American Journal of Gastroenterology. 2001 June; 96(6): 1860-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419840&dopt=Abstract

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Postoperative fistula of the abdominal wall after laparascopic cholecystectomy due to lost gallstones. Author(s): Weiler H, Grandel A. Source: European Journal of Ultrasound : Official Journal of the European Federation of Societies for Ultrasound in Medicine and Biology. 2002 June; 15(1-2): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044854&dopt=Abstract

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Practical recommendations for the prediction and management of common bile duct stones in patients with gallstones. Author(s): Kama NA, Atli M, Doganay M, Kologlu M, Reis E, Dolapci M. Source: Surgical Endoscopy. 2001 September; 15(9): 942-5. Epub 2001 June 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443474&dopt=Abstract

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Predicting the composition of gallstones by infrared spectroscopy. Author(s): Gokulakrishnan S, Murugesan R, Mathew S, Prasanthi R, Ashok AC, Ramesh H, Sivakumar G, Surendran R, Jayanthi V. Source: Trop Gastroenterol. 2001 April-June; 22(2): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552492&dopt=Abstract

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Recurrent abscess at site of laparoscopic cholecystectomy port due to spilled gallstones. Author(s): Narreddy SR, Guleria S, Agarwal S, Svr CM, Mandal S. Source: Indian J Gastroenterol. 2001 July-August; 20(4): 161. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497181&dopt=Abstract

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Recurrent staphylococcal bacteraemia and subhepatic abscess associated with gallstones spilled during laparoscopic cholecystectomy two years earlier. Author(s): Van Mierlo PJ, De Boer SY, Van Dissel JT, Arend SM. Source: The Netherlands Journal of Medicine. 2002 May; 60(4): 177-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164397&dopt=Abstract

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Remote complications of spilled gallstones during laparoscopic cholecystectomy: causes, prevention, and management. Author(s): Hawasli A, Schroder D, Rizzo J, Thusay M, Takach TJ, Thao U, Goncharova I. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2002 April; 12(2): 123-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019573&dopt=Abstract

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Reply: Gallstones, cholecystectomy, and the risk for developing pancreatic cancer. Author(s): Bosetti C, Negri E, Franceschi S, La Vecchia C. Source: British Journal of Cancer. 2003 January 13; 88(1): 159-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556976&dopt=Abstract

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Review article: agents affecting gall-bladder motility--role in treatment and prevention of gallstones. Author(s): van Erpecum KJ, Venneman NG, Portincasa P, Vanberge-Henegouwen GP. Source: Alimentary Pharmacology & Therapeutics. 2000 May; 14 Suppl 2: 66-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903008&dopt=Abstract

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Review: pathogenesis of gallstones. Author(s): Dowling RH. Source: Alimentary Pharmacology & Therapeutics. 2000 May; 14 Suppl 2: 39-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903002&dopt=Abstract

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Risk factors and pathogenesis of cholesterol gallstones: state of the art. Author(s): Amigo L, Zanlungo S, Mendoza H, Miquel JF, Nervi F. Source: Eur Rev Med Pharmacol Sci. 1999 November-December; 3(6): 241-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261734&dopt=Abstract

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Risk factors for hyperbilirubinemia and gallstones in Chinese patients with b thalassemia syndrome. Author(s): Au WY, Cheung WC, Chan GC, Ha SY, Khong PL, Ma ES. Source: Haematologica. 2003 February; 88(2): 220-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604413&dopt=Abstract

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Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study. Author(s): Acalovschi M, Blendea D, Feier C, Letia AI, Ratiu N, Dumitrascu DL, Veres A. Source: The American Journal of Gastroenterology. 2003 August; 98(8): 1856-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907344&dopt=Abstract

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Single and multiple cholesterol gallstones and the influence of bacteria. Author(s): Vitetta L, Best SP, Sali A. Source: Medical Hypotheses. 2000 December; 55(6): 502-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090298&dopt=Abstract

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Sonographic evaluation of gallbladder volume and ejection fraction in obese women without gallstones. Author(s): Sari R, Balci MK, Coban E, Karayalcin U. Source: Journal of Clinical Ultrasound : Jcu. 2003 September; 31(7): 352-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923879&dopt=Abstract

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Spilled gallstones after laparoscopic cholecystectomy. Author(s): Papasavas PK, Caushaj PF, Gagne DJ. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2002 October; 12(5): 383-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470414&dopt=Abstract

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Spontaneous hepatic hemorrhage secondary to retained intraperitoneal gallstones. Author(s): Jost CJ, Smith JL, Smith RS. Source: The American Surgeon. 2000 November; 66(11): 1059-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090019&dopt=Abstract

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Structural analysis of gallstones with thin-section petrographic microscopy: a study of 100 gallstones from Taiwanese patients. Author(s): Liu JS, Huang CS, Lien HH. Source: The Journal of Laboratory and Clinical Medicine. 2002 December; 140(6): 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486405&dopt=Abstract

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Surgical treatment of gallstones: changes in a defined population during a 20-year period. Author(s): Persson GE, Ros AG, Thulin AJ. Source: The European Journal of Surgery = Acta Chirurgica. 2002; 168(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022365&dopt=Abstract

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Symptomatic gallstones in patients with spinal cord injury. Author(s): Tola VB, Chamberlain S, Kostyk SK, Soybel DI. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2000 November-December; 4(6): 642-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307101&dopt=Abstract

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The Amerindian epidemics of cholesterol gallstones: the North and South connection. Author(s): Nervi F, Miquel JF, Marshall G. Source: Hepatology (Baltimore, Md.). 2003 April; 37(4): 947-8; Author Reply 948-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668992&dopt=Abstract

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The color of gallstones: yellow, brown or black. Present features of Korean gallstone disease. Author(s): Shim CS. Source: Gastrointestinal Endoscopy. 2000 July; 52(1): 144-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882987&dopt=Abstract

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The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study. Author(s): Portincasa P, Altomare DF, Moschetta A, Baldassarre G, Di Ciaula A, Venneman NG, Rinaldi M, Vendemiale G, Memeo V, vanBerge-Henegouwen GP, Palasciano G. Source: The American Journal of Gastroenterology. 2000 December; 95(12): 3444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151875&dopt=Abstract

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The fate of gallstones: traditional practice questioned. Author(s): Tamhankar AP, Nigam K, Houghton PW. Source: Annals of the Royal College of Surgeons of England. 2003 March; 85(2): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648339&dopt=Abstract

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Treatment of gallstones by extracorporeal shock wave lithotripsy. Author(s): Ertan A. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 831-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003415&dopt=Abstract

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Unretrieved gallstones presenting as a Streptococcus bovis liver abscess. Author(s): Steerman PH, Steerman SN. Source: Jsls. 2000 July-September; 4(3): 263-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987408&dopt=Abstract

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Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group. Author(s): Petroni ML, Jazrawi RP, Pazzi P, Lanzini A, Zuin M, Pigozzi MG, Fracchia M, Galatola G, Alvisi V, Heaton KW, Podda M, Northfield TC. Source: Alimentary Pharmacology & Therapeutics. 2001 January; 15(1): 123-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136285&dopt=Abstract

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Value of prone positioning in the ultrasonographic diagnosis of gallstones: prospective study. Author(s): Hough DM, Glazebrook KN, Paulson EK, Bowie JD, Foster WL. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2000 September; 19(9): 633-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10972560&dopt=Abstract

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What is the risk of biliary pancreatitis in patients with gallstones? Author(s): Lowenfels AB, Lankisch PG, Maisonneuve P. Source: Gastroenterology. 2000 September; 119(3): 879-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023362&dopt=Abstract

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

Finding Nutrition Studies on Gallstones 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 “gallstones” (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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Gallstones

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

A case-control study of gallstones: a major risk factor for biliary tract cancer. Author(s): Division of Epidemiology, Aichi Cancer Center Research Institute, Kanokoden, Nagoya. Source: Kato, I Kato, K Akai, S Tominaga, S Jpn-J-Cancer-Res. 1990 Jun-July; 81(6-7): 57883 0910-5050

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A radical view of gallstone aetiogenesis. Author(s): Department of Medicine, Royal Infirmary, Manchester, UK. Source: Braganza, J M Worthington, H Med-Hypotheses. 1995 November; 45(5): 510-6 0306-9877

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A useful cholesterol solvent for medical dissolution of gallstones. Author(s): Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. Source: Igimi, H Watanabe, D Yamamoto, F Asakawa, S Toraishi, K Shimura, H Gastroenterol-Jpn. 1992 August; 27(4): 536-45 0435-1339

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Administration of a terpene mixture inhibits cholesterol nucleation in bile from patients with cholesterol gallstones. Source: von Bergmann, K Beck, A Engel, C Leiss, O Klin-Wochenschr. 1987 May 15; 65(10): 458-62 0023-2173

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Altered cholesterol metabolism in patients with cholesterol gallstones: responses to reduced dietary cholesterol. Source: Kern, F Trans-Am-Clin-Climatol-Assoc. 1992; 104235-40 0065-7778

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Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer and prevents the formation of cholesterol gallstones in inbred mice. Author(s): Department of Gastroenterology, Sourasky Tel Aviv Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Israel. [email protected] Source: Gilat, T Leikin Frenkel, A Goldiner, L Laufer, H Halpern, Z Konikoff, F M Lipids. 2001 October; 36(10): 1135-40 0024-4201

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Ascorbic acid and cholesterol gallstones. Author(s): General Internal Medicine Section (111A1), San Francisco VA Medical Center, CA 94121. Source: Simon, J A Med-Hypotheses. 1993 February; 40(2): 81-4 0306-9877

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Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Author(s): School of Public Health, University of Chile, Santiago, Chile. [email protected] Source: Serra, I Yamamoto, M Calvo, A Cavada, G Baez, S Endoh, K Watanabe, H Tajima, K Int-J-Cancer. 2002 December 1; 102(4): 407-11 0020-7136

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Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for the dissolution of calcified gallstones. Author(s): Department of Surgery, Chugoku Rosai Hospital, Hiroshima, Japan. Source: Takahashi, M Konishi, T Maeda, Y Fukuzawa, M Nishida, T Ohya, T Katayama, K Kakehi, N Sakakura, H Takagi, A Maeda, M Ohama, H Biol-Pharm-Bull. 1998 June; 21(6): 551-7 0918-6158

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By the way, doctor. Last month I had a night of severe abdominal pain. My doctor ordered an ultrasound test, and it showed gallstones. She is recommending surgery to remove my gallbladder, but I'd rather not have an operation because of this one

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episode. Is it dangerous to hold off on surgery? Is there any diet to follow or medicine I can take to prevent another attack? I am 53 years old and healthy. Source: Goldfinger, S E Harv-Health-Lett. 1999 August; 24(10): 3 1052-1577 •

Caffeine prevents cholesterol gallstone formation. Author(s): Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Md. Source: Lillemoe, K D Magnuson, T H High, R C Peoples, G E Pitt, H A Surgery. 1989 August; 106(2): 400-6; discussion 406-7 0039-6060

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Cholelithiasis in owl monkeys: seven cases. Source: Baer, J.F. Weller, R.E. Dagle, G.E. Malaga, C.A. Lee, S.P. Lab-Anim-Sci. Cordova, Tenn. : American Association for Laboratory Animal Science. November 1990. volume 40 (6) page 629-633. 0023-6764

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Cholesterol-lowering and gallstone-preventing action of chitosans with different degrees of deacetylation in hamsters fed-cholesterol-rich diets. Source: Trautwein, E.A. Jurgensen, U. Erbersdobler, H.F. Nutr-res. New York, N.Y. : Elsevier Science Inc. June 1997. volume 17 (6) page 1053-1065. 0271-5317

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Clinical manifestations of gallstone disease: evidence from the multicenter Italian study on cholelithiasis (MICOL). Author(s): Department of Medicine and Ageing, University of Chieti “G. d'Annunzio”, Italy. [email protected] Source: Festi, D Sottili, S Colecchia, A Attili, A Mazzella, G Roda, E Romano, F Hepatology. 1999 October; 30(4): 839-46 0270-9139

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Comparative morphology of the gallbladder and biliary tract in vertebrates: variation in structure, homology in function and gallstones. Author(s): Department of Biological Sciences, Kent State University, Ohio 44242, USA. Source: Oldham Ott, C K Gilloteaux, J Microsc-Res-Tech. 1997 September 15; 38(6): 57197 1059-910X

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Comparative studies on iodine levels in gallstones and bile of Japanese and Thais (Chiang Mai and Bangkok). Author(s): Center for Digestive Diseases, Second Hospital, Nippon Medical School, Kawasaki, Japan. Source: Naito, E Pausawasdi, A Miki, M Tanaka, M J-Med-Assoc-Thai. 1999 April; 82(4): 374-82 0125-2208

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Comparison of effects of cholecystokinin and erythromycin on bile chemistry and gallstone formation in aged guinea pigs. Author(s): Department of Internal Medicine, Gulhane Medical Faculty, Hacettepe University, Ankara, Turkey. [email protected] Source: Mas, Mehmet Refik Ateskan, Umit Doruk, Huseyin Kocabalkan, Fikri Comert, Bilgin Mas, Nuket Ahmed, Hafez Indian-J-Gastroenterol. 2002 Jan-February; 21(1): 4-6 0254-8860

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Diet and gallstones in women of a rural town of Sicily. Source: Montalto, G. Carroccio, A. Soresi, M. Cartabellotta, A. Lorello, D. Cavera, G. Averna, M.R. Barbagallo, C.M. Anastasi, G. Bascone, F. J-nutr-environ-med. Abingdon, U.K. : Carfax Publishing Company. June 1997. volume 7 (2) page 101-106. 1359-0847

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Diet, physical activity, and gallstones--a population-based, case-control study in southern Italy. Author(s): Laboratorio di Epidemiologia e Biostatistica, Istituto di Ricovero e Cura a Carattere Scientifico S De Bellis, Ospedale Specializzato in Gastroenterologia, Castellana, Bari, Italy. Source: Misciagna, G Centonze, S Leoci, C Guerra, V Cisternino, A M Ceo, R Trevisan, M Am-J-Clin-Nutr. 1999 January; 69(1): 120-6 0002-9165

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Dietary fibre and gallstones. Source: Judd, P.A. Dietary fibre perspectives : reviews and bibliography 1 / edited by Anthony R. Leeds; bibliographical editor Alison Avenell; foreword by D.P. Burkitt. London : John Libbey, 1985. page 40-46. ISBN: 0861960521

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Dietary fish oil inhibits cholesterol monohydrate crystal nucleation and gallstone formation in the prairie dog. Author(s): Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Md, USA. Source: Magnuson, T H Lillemoe, K D High, R C Pitt, H A Surgery. 1995 September; 118(3): 517-23 0039-6060

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Differences between hepatic and biliary lipid metabolism and secretion in genetically gallstone-susceptible and gallstone-resistant mice. Author(s): Department of Gastroenterology, First Affiliated Hospital, Medical College of Zhejiang University,79 Qing Chun Road, Hangzhou 310003, China. [email protected] Source: Xu, G Zhao, L Fuchs, M Chin-Med-J-(Engl). 2002 September; 115(9): 1292-5 03666999

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Dissolution of cholesterol gallstones in mice by the oral administration of a fatty acid bile acid conjugate. Author(s): Minerva Center for Cholesterol Gallstones and Lipid Metabolism in the Liver, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. [email protected] Source: Gilat, Tuvia Leikin Frenkel, Alicia Goldiner, Ilana Halpern, Zamir Konikoff, Fred M Hepatology. 2002 March; 35(3): 597-600 0270-9139

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Effect of dietary consumption, advanced age and overweight on the physical characteristics of cholesterol gallstones and biliary lipid composition in west Algerian women. Author(s): Laboratoire de Nutrition Clinique et Metabolique, Departement de Biologie, Faculte des Sciences, Universite d'Oran Es-Senia, Dijon, France. Source: Lamri Senhadji, M Y Mekki, K El Kebir, B Bachir Bouiadjra, N Bouchenak, M Belleville, J Ann-Nutr-Metab. 2002; 46(3-4): 139-46 0250-6807

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Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn's disease. Author(s): Department of Gastrointestinal and Liver Diseases, Academic Medical Center, Amsterdam, The Netherlands. [email protected] Source: Brink, M A Slors, J F Keulemans, Y C Mok, K S De Waart, D R Carey, M C Groen, A K Tytgat, G N Gastroenterology. 1999 June; 116(6): 1420-7 0016-5085

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Epidemiological correlation between chromium content in gallstones and cholesterol in blood. Author(s): Center for Digestive Diseases, Second Hospital, Nippon Medical School, Kawasaki, Japan.

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Source: Shigeta, Akiko Ratanamaneechat, Supachai Srisukho, Songphol Tanaka, Mikio Moriyama, Yukichi Suwanagool, Surapol Miki, Masaru J-Med-Assoc-Thai. 2002 February; 85(2): 183-94 0125-2208 •

Evaluation of garlic oil as a contact dissolution agent for gallstones: comparison with monooctanoin. Author(s): Department of Gastroenterology, SMS Medical College, Jaipur, India. Source: Nijhawan, S Agarwal, V Sharma, D Rai, R R Trop-Gastroenterol. 2000 OctDecember; 21(4): 177-9 0250-636X

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Gallbladder contractility and gallstone formation in the Richardson Ground Squirrel. Author(s): Department of surgery, Showa University Fujigaoka Hospital, Yokohama, Japan. Source: Ono, K Nakayoshi, A Suzuki, K Scott, G W Clanachan, A S Gastroenterol-Jpn. 1990 February; 25(1): 93-103 0435-1339

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Gallstone formation in cholestanol-fed mice. Author(s): Department of Physiological Chemistry and Nutrition, Faculty of Medicine, University of Tokyo. Source: Kim, K S Kano, K Hirabayashi, N Shefer, S Salen, G Seyama, Y J-Biochem(Tokyo). 1993 April; 113(4): 420-4 0021-924X

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Gallstones and diet in Tel Aviv and Gaza. Source: Gilat, T. Horwitz, C. Halpern, Z. Bar Itzhak, A. Feldman, C. Am-J-Clin-Nutr. Bethesda, Md. : American Society for Clinical Nutrition. February 1985. volume 41 (2) page 336-342. ill., charts. 0002-9165

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Gallstones and risk of colonic cancer: a matched case-control study. Source: Gafa, M Sarli, L Sansebastiano, G Lupi, M Longinotti, E Rigamonti, P P Peracchia, A Int-Surg. 1987 Jan-March; 72(1): 20-4 0020-8868

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Gallstones in acromegalic patients undergoing different treatment regimens. Author(s): KVB-Klinik, Konigstein. Source: Schmidt, K Leuschner, M Harris, A G Althoff, P H Jacobi, V Jungmann, E Schumm Draeger, P M Rau, H Braulke, C Usadel, K H Clin-Investig. 1992 July; 70(7): 556-9 0941-0198

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Gallstones. An epidemiological investigation. Source: Jorgensen, T Dan-Med-Bull. 1990 August; 37(4): 336-46 0907-8916

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I am a 54-year-old woman who has gone through menopause. Six months after starting HRT, I discovered I had gallstones, after suffering four attacks. I am not interested in having my gallbladder out, and I have drastically reduced the amount of fat in my diet, which has eliminated further attacks. However, I have also read that there is a link between estrogen and gallstone formation. Should I stop taking the estrogen? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 October; 6(2): 8 1070910X

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In vitro dissolution of cholesterol gallstones. Author(s): Corporate Research & Development Laboratory, E-Z-EM, Inc., Westbury, New York. Source: Sternal, R S Davis, M A Invest-Radiol. 1992 December; 27(12): 1040-3 0020-9996

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Increased total and free ionized calcium in a canine model of pigment gallstones. Author(s): Department of Surgery, Northwestern University Medical School, Chicago, Ill. Source: Dawes, L G Nahrwold, D L Rege, R V Surgery. 1988 July; 104(1): 86-90 0039-6060

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Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice. Author(s): Jackson Laboratory, Bar Harbor, Maine 04609, USA. Source: Wittenburg, Henning Lammert, Frank Wang, David Q H Churchill, Gary A Li, Renhua Bouchard, Guylaine Carey, Martin C Paigen, Beverly Physiol-Genomics. 2002 February 11; 8(1): 67-77 1094-8341

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Interleukin-4 deficiency promotes gallstone formation. Author(s): Gill Heart Institute, Division of Cardiovascular Medicine, Division of Hematology/Oncology, University of Kentucky, Lexington, KY 40536, USA. Source: King, V L Szilvassy, S J Daugherty, A J-Lipid-Res. 2002 May; 43(5): 768-71 00222275

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Lith genes control mucin accumulation, cholesterol crystallization, and gallstone formation in A/J and AKR/J inbred mice. Author(s): Department of Medicine III, University Hospital Aachen, Aachen University, Germany. [email protected] Source: Lammert, F Wang, D Q Wittenburg, H Bouchard, G Hillebrandt, S Taenzler, B Carey, M C Paigen, B Hepatology. 2002 November; 36(5): 1145-54 0270-9139

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Lovastatin alters biliary lipid composition and dissolves gallstones: a long-term study in prairie dogs. Author(s): Department of Surgery, MCP Hahnemann University, Philadelphia, Pennsylvania 19102, USA. Source: Abedin, M Z Narins, S C Park, E H Smith, P R Kirkwood, K S Dig-Dis-Sci. 2002 October; 47(10): 2192-210 0163-2116

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Lovastatin and gallstone dissolution: a preliminary study. Author(s): Research Service, Sepulveda Veterans Administration Medical Center, Calif. Source: Saunders, K D Cates, J A Abedin, M Z Roslyn, J J Surgery. 1993 January; 113(1): 28-35 0039-6060

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Measurement of calcium content of gallstones by computed tomography and the relationship between gallbladder function and calcification of gallstones. Author(s): Third Department of Internal Medicine, Hirosaki University School of Medicine, Japan. Source: Yoneda, M Tamasawa, N Makino, I Takebe, K Sakuraba, K Tamura, T Gastroenterol-Jpn. 1990 August; 25(4): 478-84 0435-1339

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Mercury content in the gallstones and bile of Thai people (Chiang Mai and Bangkok) and Japanese. Author(s): Department of Surgery, Faculty of Medicine, Chiang Mai University, Thailand. Source: Srisukho, S Prathnadi, P Suprasert, S Pausawasdi, A Naitoh, E Tasaki, T Tanaka, M Miki, M J-Med-Assoc-Thai. 1996 May; 79(5): 299-308 0125-2208

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New strategies for the treatment of gallstone disease. Author(s): Dept. of Gastroenterology, University Medical Center, Utrecht, The Netherlands. [email protected] Source: Keulemans, Y C Venneman, N G Gouma, D J van Berge Henegouwen, G P Scand-J-Gastroenterol-Suppl. 2002; (236): 87-90 0085-5928

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No association between gallstones and gastroesophageal reflux disease. Author(s): Department of Veterans Affairs Medical Center, Albuquerque, New Mexico 87108, USA.

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Source: Avidan, B Sonnenberg, A Schnell, T G Sontag, S J Am-J-Gastroenterol. 2001 October; 96(10): 2858-62 0002-9270 •

Pathogenesis of gallstones in India. Source: Tandon, R K Trop-Gastroenterol. 1988 Apr-June; 9(2): 83-93 0250-636X

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Prevalence of cholelithiasis: results of an epidemiologic investigation in Vidauban, southeast France. General Practitioner's Group of Vidauban. Author(s): Department of Gastroenterology and Radiology, University of Nice, France. Source: Caroli Bosc, F X Deveau, C Harris, A Delabre, B Peten, E P Hastier, P Sgro, E Caroli Bosc, C Stoia, M Demarquay, J F Dumas, R Coussement, A Delmont, J P Dig-DisSci. 1999 July; 44(7): 1322-9 0163-2116

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Prevalence of pigment gallstones in sheep. Source: Cavallini, A. Messa, C. Mangini, V. Linsalata, M. Guerra, V. Misciagna, G. Di Leo, A. Am-J-Vet-Res. Schaumburg, Ill. : American Veterinary Medical Association. December 1991. volume 52 (12) page 2043-2045. 0002-9645

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Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: results of a randomized controlled pilot study. Author(s): Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-4753, USA. Source: Wudel, L James Jr Wright, J Kelly Debelak, Jacob P Allos, Tara M Shyr, Yu Chapman, William C J-Surg-Res. 2002 January; 102(1): 50-6 0022-4804

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Quantitative study of local distribution of noncholesterol sterols and cholesterol in gallstones. Author(s): Department of Surgery, Second Hospital, Kawasaki, Japan. Source: Tasaki, T Miki, M Tanaka, M J-Gastroenterol. 1994 June; 29(3): 332-9 0944-1174

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Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice. Author(s): The Jackson Laboratory, Bar Harbor, Maine 04609, USA. [email protected] Source: Paigen, B Schork, N J Svenson, K L Cheah, Y C Mu, J L Lammert, F Wang, D Q Bouchard, G Carey, M C Physiol-Genomics. 2000 November 9; 4(1): 59-65 1094-8341

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Sex steroid induction of gallstones in the male Syrian hamster. Author(s): Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095. Source: Gilloteaux, J Kosek, E Kelly, T R J-Submicrosc-Cytol-Pathol. 1993 April; 25(2): 157-72 1122-9497

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Susceptibility to murine cholesterol gallstone formation is not affected by partial disruption of the HDL receptor SR-BI. Author(s): Department of Medicine, Gastroenterology Division, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA 02115, USA. [email protected] Source: Wang, David Q H Carey, Martin C Biochim-Biophys-Acta. 2002 July 11; 1583(2): 141-50 0006-3002

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The effect of diet on bile acid kinetics and biliary lipid secretion in gallstone patients treated with ursodeoxycholic acid. Source: Frenkiel, P.G. Lee, D.W.T. Cohen, H. Gilmore, C.J. Resser, K. Bonorris, G.G. Marks, J.W. Schoenfield, L.J. Am-J-Clin-Nutr. Bethesda, Md. : American Society for Clinical Nutrition. February 1986. volume 43 (2) page 239-250. charts. 0002-9165

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The evaluation of gallbladder function by quantitative radionuclide cholescintigraphy before and after ESWL for gallstones: preliminary report. Author(s): Department of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan, Republic of China. Source: Kao, C H Wang, S J Liu, T J Wu, C C Abdom-Imaging. 1993 Fall; 18(4): 325-8 0942-8925

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The fate of retained gallstones following laparoscopic cholecystectomy in a prairie dog model. Author(s): Department of Surgery, David Grant USAF Medical Center, Travis Air Force Base, California, USA. Source: Bonar, J P Bowyer, M W Welling, D R Hirsch, K J-Soc-Laparoendosc-Surg. 1998 Jul-September; 2(3): 263-8 1086-8089

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The potential site of disordered gallbladder contractility during the early stage of cholesterol gallstone formation. Author(s): Department of Physiology, Faculty of Medicine, Mansoura University, Egypt. Source: Mansour, A Dawoud, I Gad El Hak, N Hepatogastroenterology. 1998 SepOctober; 45(23): 1404-9 0172-6390

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The preventive effect of vitamin E on gallstone formation. (3). A study of the biliary lipids in patients with gallstones. Source: Saito, T Tanimura, H Nippon-Geka-Hokan. 1987 May 1; 56(3): 276-88 0003-9152

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The relationship between serum lipids, nucleation time, and biliary lipids in patients with gallstones. Author(s): Abteilung Innere Medizin II, Universitatsklinik Ulm. Source: Janowitz, P Wechsler, J G Kuhn, K Kratzer, W Tudyka, J Swobodnik, W Ditschuneit, H Clin-Investig. 1992 May; 70(5): 430-6 0941-0198

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The role of dietary iron in pigment gallstone formation. Source: Roslyn, J J Conter, R L Julian, E Abedin, M Z Surgery. 1987 August; 102(2): 32733 0039-6060

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The varied uses of gallstones. Source: Aronson, S M R-I-Med-J. 1991 December; 74(12): 569-70 0363-7913

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Type of gallstones and deaths from stroke and coronary heart disease among cholecystectomized patients. Author(s): Department of Public Health, School of Medicine, Fukuoka University, Japan. Source: Kono, S Ichimiya, H Tokudome, S Ikeda, M Nakayama, F Int-J-Epidemiol. 1988 March; 17(1): 82-5 0300-5771

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Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Author(s): Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi. Source: Dutta, U Garg, P K KuMarch, R Tandon, R K Am-J-Gastroenterol. 2000 Mar; 95(3): 784-7 0002-9270

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vitamins Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html

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

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Food and Diet Artichoke Alternative names: Cynara scolymus Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com

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

A useful cholesterol solvent for medical dissolution of gallstones. Author(s): Igimi H, Watanabe D, Yamamoto F, Asakawa S, Toraishi K, Shimura H. Source: Gastroenterol Jpn. 1992 August; 27(4): 536-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1526435&dopt=Abstract

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Adjuvant herbal treatment for gallstones. Author(s): Hoffmann J, Raahave D. Source: The British Journal of Surgery. 1993 July; 80(7): 945. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8369949&dopt=Abstract

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Adjuvant herbal treatment for gallstones. Author(s): Johnston PW.

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Source: The British Journal of Surgery. 1992 August; 79(8): 845. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1393494&dopt=Abstract •

Adjuvant herbal treatment for gallstones. Author(s): Everson NW. Source: The British Journal of Surgery. 1992 July; 79(7): 713-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1643497&dopt=Abstract

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Adjuvant herbal treatment for gallstones. Author(s): Savage AP, O'Brien T, Lamont PM. Source: The British Journal of Surgery. 1992 February; 79(2): 168. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1555068&dopt=Abstract

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Advances in the treatment of cholelithiasis by expulsion of the gallstones. Author(s): He RL. Source: J Tradit Chin Med. 1986 June; 6(2): 135-40. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3534469&dopt=Abstract

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Alimentary production of gallstones in hamsters. 17. Influence of butter fat and the fat of a dietetic margarine rich in linoleic acid on gallstone formation and composition of the bladder bile. Author(s): Dam H, Prange I, Christensen F. Source: Zeitschrift Fur Ernahrungswissenschaft. 1965 November; 6(2): 97-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5871056&dopt=Abstract

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Alimentary production of gallstones in hamsters. 20. Influence of dietary cholesterol on gallstone formation. Author(s): Dam H, Prange I, Sondergaard E. Source: Zeitschrift Fur Ernahrungswissenschaft. 1968 May; 9(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5672414&dopt=Abstract

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Alimentary production of gallstones in hamsters. 23. Influence of hydrogenated palm oil and hydrogenated palm oil in mixture with sunflower seed oil, on the ratio between lipid-soluble phosphorus and cholesterol in the bladder bile. Author(s): Prange I, Dam H. Source: Zeitschrift Fur Ernahrungswissenschaft. 1971 December; 10(4): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5161169&dopt=Abstract

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Alimentary production of gallstones in hamsters. 27. Influence of supplementation of the gallstone producing diet with squalene, cholesterol, certain other sterols, fish oil fatty acid ethyl esters, and modification of the basal diet on gallstone production and levels of cholesterol in serum and liver. Author(s): Dam H, Prange I, Sondergaard E.

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Source: Zeitschrift Fur Ernahrungswissenschaft. 1974 December; 13(4): 208-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4615449&dopt=Abstract •

APF/CBP, the small, amphipathic, anionic protein(s) in bile and gallstones, consists of lipid-binding and calcium-binding forms. Author(s): Lafont H, Domingo N, Groen A, Kaler EW, Lee SP, Koehler R, Ostrow JD, Veis A. Source: Hepatology (Baltimore, Md.). 1997 May; 25(5): 1054-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9141417&dopt=Abstract

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Apple juice and the chemical-contact softening of gallstones. Author(s): Dekkers R. Source: Lancet. 1999 December 18-25; 354(9196): 2171. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609857&dopt=Abstract

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Ascorbic acid and cholesterol gallstones. Author(s): Simon JA. Source: Medical Hypotheses. 1993 February; 40(2): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8455479&dopt=Abstract

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Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Author(s): Serra I, Yamamoto M, Calvo A, Cavada G, Baez S, Endoh K, Watanabe H, Tajima K. Source: International Journal of Cancer. Journal International Du Cancer. 2002 December 1; 102(4): 407-11. Erratum In: Int J Cancer. 2003 May 10; 104(6): 798. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402311&dopt=Abstract

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Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for the dissolution of calcified gallstones. Author(s): Takahashi M, Konishi T, Maeda Y, Fukuzawa M, Nishida T, Ohya T, Katayama K, Kakehi N, Sakakura H, Takagi A, Maeda M, Ohama H. Source: Biological & Pharmaceutical Bulletin. 1998 June; 21(6): 551-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9657036&dopt=Abstract

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Can a cholesterol-lowering diet cause gallstones? Author(s): Hofmann AF, Northfield TC, Thistle JL. Source: The New England Journal of Medicine. 1973 January 4; 288(1): 46-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4681901&dopt=Abstract

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Chemical dissolution of gallstones in Taiwan: an in vitro study. Author(s): Lin XZ, Chou TC, Lin PW, Chou YL, Li CC, Chen SK.

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Source: Journal of Gastroenterology and Hepatology. 1994 March-April; 9(2): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8003647&dopt=Abstract •

Cholelithiasis in mice: effects of different chemicals upon formation and prevention of gallstones. Author(s): Goswami SK, Frey CF. Source: The Journal of Surgical Research. 1974 February; 16(2): 164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4818342&dopt=Abstract

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Cholesterol precursor sterols, plant sterols, and cholestanol in human bile and gallstones. Author(s): Miettinen TA, Kesaniemi YA, Jarvinen H, Hastbacka J. Source: Gastroenterology. 1986 April; 90(4): 858-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3081398&dopt=Abstract

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Current treatment modalities for symptomatic gallstones. Author(s): Plaisier PW, van der Hul RL, Terpstra OT, Bruining HA. Source: The American Journal of Gastroenterology. 1993 May; 88(5): 633-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8480723&dopt=Abstract

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Diet and gallstones in Italy: the cross-sectional MICOL results. Author(s): Attili AF, Scafato E, Marchioli R, Marfisi RM, Festi D. Source: Hepatology (Baltimore, Md.). 1998 June; 27(6): 1492-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9620318&dopt=Abstract

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Disappearing gallstones. Author(s): Thorley K. Source: Lancet. 1984 June 2; 1(8388): 1247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6144968&dopt=Abstract

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Dissolution of calcified gallstones. Part II. Evaluation of edetic acid preparations for dissolution of residue after in vitro methyl tert-butyl ether treatment. Author(s): Kammer B, Brink JA, Knoefel WT, Mueller PR, Prien EL, Ferrucci JT. Source: Investigative Radiology. 1994 April; 29(4): 454-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8034452&dopt=Abstract

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Dissolution of calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether dissolution of cholesterol gallstones. Author(s): Nelson PE, Moyer TP, Thistle JL. Source: Gastroenterology. 1990 May; 98(5 Pt 1): 1345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2323524&dopt=Abstract

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Dissolution of gallstones. Author(s): Plaisier PW, Vergunst H, Terpstra OT. Source: Digestive Diseases (Basel, Switzerland). 1993; 11(3): 181-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8370143&dopt=Abstract

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Does spinal manipulation really cure gallstones? Alternative medicine and the general surgeon. Author(s): Zannis VJ. Source: American Journal of Surgery. 2000 December; 180(6): 389-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182384&dopt=Abstract

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Effect of dietary consumption, advanced age and overweight on the physical characteristics of cholesterol gallstones and biliary lipid composition in west Algerian women. Author(s): Lamri-Senhadji MY, Mekki K, El Kebir B, Bachir-Bouiadjra N, Bouchenak M, Belleville J. Source: Annals of Nutrition & Metabolism. 2002; 46(3-4): 139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169857&dopt=Abstract

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Effect of pectin and cellulose on formation and regression of gallstones in hamsters. Author(s): Kritchevsky D, Tepper SA, Klurfeld DM. Source: Experientia. 1984 April 15; 40(4): 350-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6325228&dopt=Abstract

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Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones. Author(s): Smith JL, Roach PD, Wittenberg LN, Riottot M, Pillay SP, Nestel PJ, Nathanson LK. Source: Journal of Gastroenterology and Hepatology. 2000 August; 15(8): 871-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022827&dopt=Abstract

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Etiology, pathogenesis and therapy of pigment gallstones. Author(s): Leuschner U, Guldutuna S, Hellstern A. Source: Digestive Diseases (Basel, Switzerland). 1991; 9(5): 282-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1752067&dopt=Abstract

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Evaluation of garlic oil as a contact dissolution agent for gallstones: comparison with monooctanoin. Author(s): Nijhawan S, Agarwal V, Sharma D, Rai RR. Source: Trop Gastroenterol. 2000 October-December; 21(4): 177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194578&dopt=Abstract

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In vitro dissolution of cholesterol and brown pigmented gallstones: a comparison of MTBE, DMSO and BA-EDTA. Author(s): Cheng JS, Lai KH, Lo GH, Ng WW, Tam TN, Huang SM. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 September; 63(9): 667-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037641&dopt=Abstract

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In vitro dissolution of cholesterol gallstones. Author(s): Sternal RS, Davis MA. Source: Investigative Radiology. 1992 December; 27(12): 1040-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1473922&dopt=Abstract

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Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones. Author(s): LaMorte WW, Booker ML, Scott TE, Williams LF Jr. Source: Surgery. 1985 September; 98(3): 445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4035566&dopt=Abstract

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Initiating factors of gallstones, especially cholesterol stones. 3. Author(s): Hikasa Y, Matsuda S, Nagase M, Yoshinaga M, Tobe T. Source: Nippon Geka Hokan. 1969 January 1; 38(1): 107-24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5813928&dopt=Abstract

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Is vegetarianism a precipitating factor for gallstones in cirrhotics? Author(s): Jayanthi V, Malathi S, Ramathilakam B, Mathew S, Prasanthi R, Srinivasan V. Source: Trop Gastroenterol. 1998 January-March; 19(1): 21-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9641029&dopt=Abstract

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Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro. Author(s): Shimizu S, Sabsay B, Veis A, Ostrow JD, Rege RV, Dawes LG. Source: The Journal of Clinical Investigation. 1989 December; 84(6): 1990-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2592569&dopt=Abstract

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Letter: Beta-sitosterol and chenodeoxycholic acid in the treatment of cholesterol gallstones. Author(s): Gerolami A, Sarles H. Source: Lancet. 1975 October 11; 2(7937): 721. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=52107&dopt=Abstract

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Lipid metabolism in the development of cholesterol gallstones in hamsters. IV. The effect of essential phospholipids and plant sterols on the biliary lipids. Author(s): Kubota S, Kajiyama G, Sasaki H, Horiuchi I, Miyoshi A.

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Source: Hiroshima J Med Sci. 1981 December; 30(4): 301-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6765681&dopt=Abstract •

Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent. Author(s): Igimi H, Tamura R, Toraishi K, Yamamoto F, Kataoka A, Ikejiri Y, Hisatsugu T, Shimura H. Source: Digestive Diseases and Sciences. 1991 February; 36(2): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1988264&dopt=Abstract

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Monoconjugated bilirubin is a major component of hemolysis-induced gallstones in mice. Author(s): Trotman BW, Nair CR, Bernstein SE. Source: Hepatology (Baltimore, Md.). 1988 July-August; 8(4): 919-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3391522&dopt=Abstract

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Mucin glycoprotein content of human pigment gallstones. Author(s): LaMont JT, Ventola AS, Trotman BW, Soloway RD. Source: Hepatology (Baltimore, Md.). 1983 May-June; 3(3): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6840683&dopt=Abstract

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Nonsurgical removal of gallstones in China: a blend of Chinese and western medicine. Author(s): Pollak OJ. Source: Del Med J. 1981 October; 53(10): 531-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7338284&dopt=Abstract

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Nutritional aspects of gallstone formation with particular reference to alimentary production of gallstones in laboratory animals. Author(s): Dam H. Source: World Review of Nutrition and Dietetics. 1969; 11: 199-239. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4904292&dopt=Abstract

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Polymer networks in pigment and cholesterol gallstones assessed by equilibrium swelling and infrared spectroscopy. Author(s): Ohkubo H, Ostrow JD, Carr SH, Rege RV. Source: Gastroenterology. 1984 October; 87(4): 805-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6468871&dopt=Abstract

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Pure calcium carbonate gallstones in a two year old in association with prenatal calcium supplementation. Author(s): Powell RW.

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Source: Journal of Pediatric Surgery. 1985 April; 20(2): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4009360&dopt=Abstract •

Quantitative study of local distribution of noncholesterol sterols and cholesterol in gallstones. Author(s): Tasaki T, Miki M, Tanaka M. Source: Journal of Gastroenterology. 1994 June; 29(3): 332-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8061802&dopt=Abstract

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Studies of the hepatic excretory defects in essential fatty acid deficiency. Their possible relationship to the genesis of cholesterol gallstones. Author(s): Sarfeh IJ, Beeler DA, Treble DH, Balint JA. Source: The Journal of Clinical Investigation. 1974 February; 53(2): 423-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344556&dopt=Abstract

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Sunbathing and gallstones. Author(s): Pavel S. Source: Lancet. 1992 January 25; 339(8787): 241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1346190&dopt=Abstract

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The etiology of pigment gallstones. Author(s): Ostrow JD. Source: Hepatology (Baltimore, Md.). 1984 September-October; 4(5 Suppl): 215S-222S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6434394&dopt=Abstract

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The varied uses of gallstones. Author(s): Aronson SM. Source: R I Med J. 1991 December; 74(12): 569-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1763274&dopt=Abstract

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Treatment with bovine gallstones exacerbates liver damage, but enhances hepatoprotection by bear gall powder in carbon tetrachloride-intoxicated rats. Author(s): Nakashima T, Matsumoto N, Kashima K. Source: Japanese Journal of Pharmacology. 1998 March; 76(3): 271-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9593220&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

General Overview Gallbladder Disease Source: Integrative Medicine Communications; www.drkoop.com Gallstones Source: Healthnotes, Inc.; www.healthnotes.com Gallstones Source: Prima Communications, Inc.www.personalhealthzone.com Herpes Alternative names: Genital Herpes, Cold Sores Source: Prima Communications, Inc.www.personalhealthzone.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com

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Obesity Source: Integrative Medicine Communications; www.drkoop.com Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Weight Loss and Obesity Source: Healthnotes, Inc.; www.healthnotes.com •

Alternative Therapy Iridology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,709,00.html Reflexology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,730,00.html

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Chinese Medicine Lidan Paishi Pian Alternative names: Lidan Paishi Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Niuhuang Alternative names: Cow-bezoar; Calculus Bovis Source: Chinese Materia Medica

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Homeopathy Berberis Vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Calcarea Carbonica Source: Healthnotes, Inc.; www.healthnotes.com Chelidonium Majus Source: Healthnotes, Inc.; www.healthnotes.com Colocynthis Source: Healthnotes, Inc.; www.healthnotes.com

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Dioscorea Source: Healthnotes, Inc.; www.healthnotes.com Lycopodium Source: Healthnotes, Inc.; www.healthnotes.com Podophyllum Source: Healthnotes, Inc.; www.healthnotes.com •

Herbs and Supplements Boldo Alternative names: Peumus boldus Source: Healthnotes, Inc.; www.healthnotes.com Culver's Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Curcuma Longa Source: Integrative Medicine Communications; www.drkoop.com Dandelion Alternative names: Taraxacum officinale Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Alternative names: Taraxacum officinale Source: Integrative Medicine Communications; www.drkoop.com Dandelion Source: Prima Communications, Inc.www.personalhealthzone.com Dandelion Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10021,00.html Devil’s Claw Alternative names: Harpagophytum procumbens Source: Healthnotes, Inc.; www.healthnotes.com Devil's Claw Alternative names: Harpagophytum procumbens, Harpagophytum zeyheri Source: Integrative Medicine Communications; www.drkoop.com Devil's Claw Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,970,00.html

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Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc.; www.healthnotes.com Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.drkoop.com Ginger Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,787,00.html Guatteria Alternative names:.; Guatteria gaumeri Greenman Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Harpagophytum Procumbens Source: Integrative Medicine Communications; www.drkoop.com Harpagophytum Zeyheri Source: Integrative Medicine Communications; www.drkoop.com Linden Alternative names: Tilia spp. Source: Healthnotes, Inc.; www.healthnotes.com Lipotropic Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,861,00.html Lysine Source: Healthnotes, Inc.; www.healthnotes.com Lysine Source: Prima Communications, Inc.www.personalhealthzone.com Mentha X Piperita Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Alternative names: Silybum marianum, Carduus marianus Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Milk Thistle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html

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Peppermint Alternative names: Mentha piperita Source: Healthnotes, Inc.; www.healthnotes.com Peppermint Alternative names: Mentha x piperita Source: Integrative Medicine Communications; www.drkoop.com Peppermint Source: Prima Communications, Inc.www.personalhealthzone.com Peppermint Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,812,00.html Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Psyllium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,814,00.html Taraxacum Officinale Source: Integrative Medicine Communications; www.drkoop.com Taurine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10059,00.html Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc.; www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Integrative Medicine Communications; www.drkoop.com Turmeric Source: Prima Communications, Inc.www.personalhealthzone.com Turmeric Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10062,00.html Zingiber Officinale Source: Integrative Medicine Communications; www.drkoop.com

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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. CLINICAL TRIALS AND GALLSTONES Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning gallstones.

Recent Trials on Gallstones The following is a list of recent trials dedicated to gallstones.8 Further information on a trial is available at the Web site indicated. •

Lithotripsy for the Treatment of Gallstones Condition(s): Cholelithiasis Study Status: This study is terminated. Sponsor(s): Medstone International Purpose - Excerpt: The purpose of this study is to determine the effectiveness and safety of using the Medstone lithotripter to treat single non-calcified gallstones from 4 to 20 mm in diameter. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042549

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.

8

These are listed at www.ClinicalTrials.gov.

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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 “gallstones” (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/

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

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

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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

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

Patents on Gallstones By performing a patent search focusing on gallstones, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

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

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

Agents for distributing gallstones Inventor(s): Moyiyasu; Akihito (Sendai, JP) Assignee(s): Senju Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 5,441,748 Date filed: November 10, 1993 Abstract: An aqueous agent for disintegrating gallstones containing an alkali metal carbonate such as sodium or potassium hydrogen carbonate and optionally Nacetylcysteine. Excerpt(s): The present invention relates to an agent for disintegrating gallstones, and more particularly to an agent for disintegrating gallstones containing an alkali metal carbonate or a combination of an alkali metal carbonate and N-acetylcysteine as its effective components. The statistical study shows that gallstone carriers reach about 9% of the population in Japan. In 1989, the cholecystolithiasis patients were reported to be 270,000, most of whom were subjected to surgical lithectomy. The gallstones are classified into cholesterol gallstones and pigment gallstones (bilirubin calcium and black-pigment stones) based on the component thereof. Studies on an agent for dissolving gallstones have been performed for a long time, resulting in the development of formulations of bile acid such as ursodeoxycholic acid and chenodeoxycholic acid for dissolving choresterol gallstones. Clinical tests have proved that such formulations are effective for gallstone dissolution. However, actual effect for gallstone dissolution given by such formulations depends on the size of the stone and cholecyst function, whereby the patient should be dosed for a long period such as a half- year to a year or more. A suitable agent for dissolving pigment stones has not yet been developed in spite of various studies. The inventor has found out from studies on composition of the gallstones that mucopolysaccharides and mucoproteins (hereinafter abbreviated to muco-substances) play an important role as a component for binding the crystalline cholesterol or bilirubin. On the other hand, SH-compounds including N-acetylcysteine have been known to have action for splitting off the S--S bond of muco-substances. In particular, it has been reported that N-acetylcysteine accelerates dissolution of cholesterol gallstones [see Scand. J. Gastroent., 24, 373-380 (1989); Gastroenterology., 98, 454-463 (1990)]. However, this document reports that the dissolution of cholesterol gallstones takes about 10 hours to several weeks, and further that the absolute effect is small. Web site: http://www.delphion.com/details?pn=US05441748__

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Apparatus for removing gallstones and tissue during surgery Inventor(s): Washington, deceased; Charles N. (980 Terry La., late of Lake Charles, LA 70605), Washington, executrix; by Virginia Y. (980 Terry La., Lake Charles, LA 70605) Assignee(s): none reported Patent Number: 5,147,371 Date filed: June 28, 1991

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Abstract: A device for the in situ collection of surgically excised material, including whole gall bladder, gallstones, dissected gall bladder and other tissues, for removal from the body, particularly in laproscopic surgical procedures. Excerpt(s): The invention relates to a medical device for the removal of gallstones and/or gallbladder tissue, more particularly to a device particularly for use through an aperture or an opening in the patients abdomen or the like. Gallbladder disease continues to be one of the most common digestive disorders seen by physicians in this country. Approximately 500,000 cholecystectomies are performed each year in the United States. After conventional major abdominal surgery, patients experience considerable discomfort and their recovery time is lengthy. To address this problem, principles of laparoscopy have recently been applied to cholecystectomy. Therapeutic laparoscopy for gallstone disease was reported by Morris in 1988 in which he described the procedure which allowed the laparoscopist to cannulate the gallbladder directly and remove gallstones, leaving the organ in situ. Laparoscopic removal of the gallbladder was initially performed in the U.S. by Saye and McKernan in 1988. Endocholecystectomy has evolved rapidly since 1988, along with the development of laparoscopic instrumentation and advances in video technology, contributing to the improved safety and quick adoption by general surgeons of this new procedure. Because of the tremendous advantages of endocholecystectomy, this procedure may rapidly replace open cholecystectomy as the procedure of choice. Web site: http://www.delphion.com/details?pn=US05147371__ •

Apparatus for the non-intrusive fragmentation of renal calculi, gallstones or the like Inventor(s): LaRocca; Aldo (Revigliasco Torinese, IT) Assignee(s): Lara Consultants s.r.l. (IT) Patent Number: 5,209,234 Date filed: January 30, 1992 Abstract: The apparatus for the non-intrusive fragmentation of renal calculi, gallstones or the like according to the invention comprises at least one ultrasonic receivertransmitter head (12) focused on the renal calculus (11), gallstone or the like to be disintegrated, a head (12) being associated with a low-power variable frequency transmitter (16) and with a receiver (18) to perform a spectral analysis of the characteristic resonance frequencies of the renal calculus (11), gallstone or the like to be disintegrated, and a controller (Tx1, OSC1) to cause a transmitter (16) to emit relatively high-power energy peaks at the characteristic resonance frequencies of the renal calculus (11), gallstone or the like to promote its disintegration. Excerpt(s): This invention relates to an apparatus for the non-intrusive fragmentation of renal calculi, gallstones or the like. It is well known that the conventional method of removing renal calculi, gallstones or the like is by surgery. Recently however, much effort has been dedicated to the search for non-sanguinary and in particular nonintrusive techniques for fragmenting renal calculi in such a manner as to disintegrate their structure and break them down into particles which can be eliminated naturally without inconveniencing the patient. Web site: http://www.delphion.com/details?pn=US05209234__

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Apparatus, and method for chemical contact dissolution of gallstones Inventor(s): Zakko; Salam F. (Farmington, CT) Assignee(s): Development Collaborative Corporation (Hamden, CT) Patent Number: 5,514,088 Date filed: June 2, 1995 Abstract: A fully automatic organ pressure sensitive apparatus for dislodging and removing obstructions in bodily cavities or organs by both delivering and removing fluid thereto, operable by high rate continuous or intermittent infusion of fluid solvent over a set pressure range to effect rapid dissolution and removal of the obstruction without complications to the patient. By continuous feedback monitoring of fluid pressure in the bodily organ or cavity of interest, the apparatus can constantly vary infusion and aspiration rates to maintain the set pressure range. If the pressure persists above or below the set range, the apparatus activates a safety feature leading to a period of maximal aspiration and cessation of infusion, followed by cessation of solvent transfer and triggering of an alarm to alert the operator. Excerpt(s): For most individuals who suffer from gallstones, the treatment of choice is to have a cholecystectomy, or surgical removal of the gallbladder. Each year 500,000 such operations are done in the United States alone. Recently, because of the cost, prolonged recuperation time and possible side effects associated with this surgery, methods have been developed for chemically removing gallstones in situ. Generally, this procedure involves inserting a catheter into the gallbladder followed by infusing a chemical solvent capable of dissolving the gallstone. The procedure thus avoids the need for and attendant risk of surgery. A variety of chemical solvents have been tried and found to exhibit varying efficiencies of gallstone dissolution, depending on the chemical nature of the gallstone. Gallstones are generally composed of cholesterol or calcium salts, particularly calcium bilirubinate and calcium carbonate. Lipid solvents are effective at dissolving cholesterol gallstones, whereas these solvents have little or no solubilizing effect on gallstones composed of calcium salts. Thus, diethyl ether readily dissolves cholesterol gallstones, and other solvents such as mono-octanoin, and octadiol (glyceryl-1-octyl ether) also have good solubilizing properties. Unfortunately, few if any solvents are satisfactory for dissolving calcium gallstones. The invention herein will therefore find principal utility in cholesterol gallstone removal. It has been recognized that ether compounds such as diethylether have excellent cholesterol solubilizing properties, low viscosity and very good kinetic solubility but diethylether is hazardous since it boils below body temperature. Recently methyl tert-butyl ether (MTBE), a solvent hithertofore used primarily as a gasoline additive and a chromatographic solvent media, has been used for gallstone dissolution since it exhibits all the properties of ethers. Moreover, MTBE boils above body temperature and the solvent rapidly dissolves the gallstones without damaging the mucosa of the gallbladder. The effectiveness of such new solvents has led to considerable activity focused on developing apparatus and methods for delivering MTBE and similar solvents to patients suffering from gallstones in ways to most rapidly and effectively solubilize gallstones without the complications arising from introducing such solvents into the body. (For brevity herein, the description will be with respect to use of the MTBE as a solvent. It will be recognized, however, that this invention will be applicable to a number of different solvents). Web site: http://www.delphion.com/details?pn=US05514088__

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Cholagogue and/or gallstone solubilizer Inventor(s): Uji; Akira (Hirakata, JP) Assignee(s): Hiya Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 4,931,475 Date filed: December 10, 1985 Abstract: A cholagogic and/or gallstone solubilizer comprising a borneol compound as its active component. Excerpt(s): The present invention relates to a cholagogue and/or a gallstone solubilizer comprising a borneol compound as the active component thereof. Unexpectedly, there are a wide variety of bile duct and gallbladder diseases which include cholangitis, cholecystitis, biliary dys-kinesia (bile filling up the gall bladder, discharge function disorder), cholelithiasis, etc., and these diseases not infrequently develop into chronic diseases. Operations encounter difficulties and do not always afford good results. Accordingly, it is important to use cholagogues and like agents for causing bile to normally flow into the duodenum via the bile duct without stagnation, for preventing formation of gallstones and for dissolving gallstones for treatment. Web site: http://www.delphion.com/details?pn=US04931475__

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Cholecystoscopic cannula and cholecystoscopic gallbladder laser-sclerosis procedure Inventor(s): Kleiman; Aldo Sergio (Blas Parera St. No. 910, City of Rosario, Province of Santa Fe, AR) Assignee(s): none reported Patent Number: 5,860,426 Date filed: November 6, 1996 Abstract: A cholecystoscopic laser-sclerosis surgical procedure for the elimination of a human gallbladder in a single session using a local anesthesia, which utilizes a speciallydesigned cholecystoscopic cannula to couple the gallbladder fundus to the cannula by forcing a ring of gallbladder tissue into a groove in the cannula, by performing an operative endoscopy inside the gallbladder, closing the cystic duct meatus using a forceps, sealing the cystic duct using electrocoagulation, removing the gallstones, ablating the mucous membrane of the gallbladder by using a CO2 laser, injecting a biological cement into the gallbladder, applying a vacuum in order to collapse the gallbladder, eliminating the gallbladder tissue within the cannula by using a CO2 laser or electrocoagulation, and finally, releasing the coupling of the cannula to the gallbladder fundus and removing the cholecystoscopic cannula. The gallbladder disappears by means of atrophy. Excerpt(s): The present invention relates to a cannula and a procedure for gallbladder elimination. 2) the percutaneous radioscopic gallbladder chemical-sclerosis (the gallbladder disappears by means of atrophy). The object of the invention is to provide a new procedure which combines the advantages of the percutaneous gallbladder chemical-sclerosis procedure, which is very mini-invasive and utilizes only a local anesthesia, with that of the cholecystectomy which is a single session procedure. Web site: http://www.delphion.com/details?pn=US05860426__

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Compositions and methods for dissolving body calculi Inventor(s): Coulter; Stephen L. (Irvine, CA), Mayhan; Kenneth G. (Irvine, CA), Morehead; Steven R. (Riverside, CA), Oviatt; Christy L. H. (Mission Viejo, CA) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 5,244,913 Date filed: November 19, 1991 Abstract: Compositions and methods for dissolving calculi deposits in humans are disclosed. The compositions include solutions of quaternary ammonium salts and are particularly effective for the contact dissolution of pigment portions of biliary tract calculi such as gallstones. The solutions preferably further include mineral chelating agent and disulfide bond cleaving agent to aid in deaggregating mineral components and glycoprotein components of calculi. Excerpt(s): The present invention relates in general to the treatment of diseases characterized by calculi deposits in humans. More particularly, the present invention is directed toward quaternary ammonium salt compositions and methods for using quaternary ammonium salt compositions for the contact dissolution or deaggregation of human gallstones having high pigment content. Each year gallstone disease inflicts large numbers of individuals worldwide. The disease is characterized by biliary colic and is frequently accompanied by obstructive jaundice or pancreatitis. Additionally, patients may experience nausea and vomiting as well as extreme abdominal pain and tenderness. These symptoms are attributed to the presence of calculi, known as biliary tract stones, or gallstones, in the gallbladder or other parts of the biliary tract. A traditional method for treating gallstone disease is to surgically remove the gallbladder with the problematic gallstones remaining intact inside the extracted gallbladder. This procedure, known as cholecystectomy, involves major abdominal surgery and many gallstone disease patients can neither tolerate the surgical intervention nor the traumatic recovery associated with the surgery. Additionally, the high cost of cholecystectomies and long post surgery recovery times make this procedure particularly unattractive. In recent years many medical practioners have turned to treatment procedures known as cholelitholysis, or methods for chemically dissolving gallstones. These dissolution techniques initially targeted gallstones having high cholesterol contents. Typically, gallstones suitable for cholelitholysis are at least 75% and generally over 80% cholesterol. One such cholesterol gallstone dissolution method involves orally administering bile acids to patients known to have mostly cholesterol gallstones. This procedure has enjoyed only limited success, and a majority of the patients do not experience complete gallstone dissolution. Moreover, signs of effective gallstone dissolution generally are not apparent until after many months of treatment. Additionally, this method is not practical for patients suffering extreme pain requiring relatively fast relief. Web site: http://www.delphion.com/details?pn=US05244913__

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Compositions of gastric acid-resistant microspheres containing buffered bile acids Inventor(s): Sipos; Tibor (Lebanon, NJ) Assignee(s): Digestive Care Inc. (Lebanon, NJ) Patent Number: 5,405,621 Date filed: November 10, 1993

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Abstract: Disclosed are gastric acid-resistant polymer-coated buffered-bile acid compositions, process for their preparations and methods of treating digestive disorders, impaired liver function, autoimmune diseases of the liver and biliary tract, preventing colon cancer, cholestasis associated with cystic fibrosis, dissolving gallstones and regulating dietary cholesterol absorption by administering said compositions to a mammal in need of such treatment. Excerpt(s): This invention relates to buffer-stabilized bile acid compositions for ingestion by a mammal, a process for preparing said compositions, and a method for treating digestive disorders, impaired liver function, autoimmune diseases of the liver and biliary tract, preventing colon cancer, cholestasis associated with cystic fibrosis, dissolving gallstones and regulating dietary cholesterol absorption by administering said compositions to a mammal in need of such treatment. It is known in the prior art that ursodeoxycholic acid (hereinafter sometimes referred to as UDCA) administered to mammals can remedy UDCA deficiency caused by various diseased conditions of the liver, such as gallstones, liver toxicity due to toxic metabolites, alcohol induced hangover, drug related toxicity, colon cancer following gallbladder surgery, and deficiency associated with poor digestion of fats and lipids in the intestine. UDCA requires the presence of certain conditions in order for it to be safe and effective as will be described hereunder. Once the exogenously introduced buffer-stabilized UDCA reaches the duodenum, another requirement must be satisfied: the buffer-stabilized UDCA must be released from its protective environment and intimately mixed with the food transferred from the stomach to effect digestion. Web site: http://www.delphion.com/details?pn=US05405621__ •

Compositions of gastric acid-resistant microspheres containing salts of bile acids Inventor(s): Sipos; Tibor (Lebanon, NJ) Assignee(s): Digestive Care Inc. (Lebanon, NJ) Patent Number: 5,415,872 Date filed: October 20, 1993 Abstract: Disclosed are buffer-stabilized gastric acid resistant polymer-coated bile salt compositions, process for their preparations and methods of treating digestive disorders, impaired liver function, autoimmune diseases of the liver and biliary tract, preventing colon cancer, cholestasis associated with cystic fibrosis, dissolving gallstones and regulating dietary cholesterol absorption by administering said compositions to a mammal in need of such treatment. Excerpt(s): This invention relates to buffer-stabilized salts of bile acid compositions for ingestion by a mammal, a process for preparing said compositions, and a method for treating digestive disorders, impaired liver function, autoimmune diseases of the liver and biliary tract, preventing colon cancer, cholestasis associated with cystic fibrosis, dissolving gallstones, and regulating dietary cholesterol absorption by administering said compositions to a mammal in need of such treatment. It is known in the prior art that ursodeoxycholic acid (hereinafter sometimes referred to as UDCA) administered to mammals can remedy various diseased conditions of the liver, gallstones, liver toxicity due to toxic metabolites, alcohol induced hang-over, drug related toxicity, colon cancer following gallbladder surgery, and deficiency associated with poor digestion of fats and lipids in the intestine. UDCA requires the presence of certain conditions in order for it to be safe and effective as will be described hereunder. Once the exogenously introduced

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UDCA reaches the duodenum, another requirement must be satisfied: the UDCA must be released from its protective environment and intimately mixed with the food transferred from the stomach to effect digestion. Web site: http://www.delphion.com/details?pn=US05415872__ •

Gallbladder stone extracting forceps for laparoscopic cholecystectomy Inventor(s): Shallman; Richard W. (118 High Meadows, Richland, WA 99352) Assignee(s): none reported Patent Number: 5,693,069 Date filed: October 3, 1995 Abstract: Forceps for grasping, crashing, and removing gallstones from the opened neck of a gallbladder which is extracted through an abdominal port site during laparoscopic surgery. The forceps include upper arms having shallow concave oval tips which include a narrower distal region, a wider central region, and a narrow proximal region. The upper arms are bowed slightly outward to allow the tips to be spring-biased against each other, or against an object held between the tips. Excerpt(s): The present invention relates generally to surgical forceps, and more specifically to surgical forceps which are particularly adapted to grasping, crushing and removing gallstones from the opened neck of a gallbladder being extracted from an abdominal port site during laparoscopic cholecystectomy. The gallbladder is a piriform (i.e., pear-shaped) sac that lies within a shallow valley on the lower portion of the liver, and which concentrates the liver's bile to aid in the digestion and absorption of fats. Occasionally, cholesterol crystallizes within the gallbladder, forming stony masses or concretions of crystals known as gallstones. These gallstones can grow to be as large as golf balls, or even larger. The stones cause intimation and pain, and can result in infection of the gallbladder. If the stones pass into the bile ducts, they can cause jaundice, pancreatitis, or even death. If symptomatic gallstones are detected, removal of the diseased gallbladder and stones is generally recommended. Removal of the gallbladder and stones is generally done by a procedure known as laparoscopic cholecystectomy. Operating ports are made in the abdomen for the insertion of laparoscopic instruments, and a laparoscopic camera allows the surgeon to view the interior of the abdominal cavity on a video monitor. The gallbladder is dissected free and is pulled to an abdominal port site. The narrow end (neck) of the gallbladder (or another portion of the gallbladder) is grasped with a clamp and pulled through the abdominal port site. A small hole is then made in the portion of the gallbladder that has been pulled through the port, the bile is sucked out, and the gallbladder is extracted from the abdomen. Web site: http://www.delphion.com/details?pn=US05693069__

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Gallstone mitigation by nutrient stimulated gallbladder contraction Inventor(s): Arrone; Louis J. (Pelham Manor, NY), Peterson; Francis J. (Apple Valley, MN) Assignee(s): Sandoz Ltd. (Basel, CH) Patent Number: 5,256,640 Date filed: September 30, 1991 Abstract: Nutritional supplements and methods of use of the supplements to maximally stimulate gallbladder contraction in patients undergoing rapid weight loss, to prevent the build up of bilary sludge and/or gallstones. Excerpt(s): This application relates to nutritional supplement compositions and methods of the use of the nutrition supplements to maximally stimulte contraction of the gallbladder in patients undergoing rapid weight loss, for the purpose of preventing the build up of bilary sludge and/or gallstones. Gallbladder disease is widespread and occurs in an estimated 20 million Americans, with over 2.5 billion dollars spent annually on surgical interventions. The etiology of gallbladder disease is complex and incompletely understood. Several key factors appear to interact for gallstone formation including obesity, biliary stasis, biliary lithogenicity and nucleation of bile solutes. The prevention or mitigation of all, or several of these factors may be helpful in minimizing the need for surgery and decrease the incidence and severity of this national health issue. Recent clinical trials have evaluated several different preventative treatments including oral chemolysis with ursodiol, which decreases the lithogenicity of the bile; cholecystokinin infusion, which decreases stasis in long-term total parenteral nutrition patients (TPN); and aspirin or anti-inflammatory drugs, which appear to decrease nucleation factors. These approaches each have shown a significant impact in decreasing the incidence of sludge as well as stone formation. Other clinical studies, have shown the development of small cholesterol gallstones in some obese patients undergoing rapid weight loss. These findings were associated with favorable conditions for gallstone formation: an increase in cholesterol saturation, an increase in nucleation factors, and an increase in biliary sludge. The increase in biliary sludge has also been reported consistently in TPN patients prior to the development of gallstones. Web site: http://www.delphion.com/details?pn=US05256640__

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Indole and dihydroindole derivatives Inventor(s): Ackermann; Jean (Riehen, CH), Aebi; Johannes (Basel, CH), Dehmlow; Henrietta (Grenzach-Wyhlen, DE), Morand; Olivier (Hegenheim, FR), Panday; Narendra (Basel, CH), Weller; Thomas (Binningen, CH) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 6,503,907 Date filed: November 20, 2001 Abstract: The present invention relates to indole derivatives, dihydroindole derivatives and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses,

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gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes. Excerpt(s): The present invention is concerned with novel indole and dihydroindole derivatives, their manufacture and their use as medicaments. 2,3-oxidosqualenelanosterol cyclase (EC 5.4.99.) is required for the biosynthesis of cholesterol, ergosterol and other sterols. Causal risk factors that directly promote the development of coronary and peripheral atherosclerosis include elevated low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), hypertension, cigarette smoking and diabetes mellitus. Other synergistic risk factors include elevated concentrations of triglyceride (TG)-rich lipoproteins, small, dense low-density lipoprotein particles, lipoprotein (a) (Lp(a)), and homocysteine. Predisposing risk factors modify the causal or conditional risk factors and thus affect atherogenesis indirectly. The predisposing risk factors are obesity, physical inactivity, family history of premature CVD, and male sex. The strong connection between coronary heart disease (CHD) and high LDL-C levels in plasma, and the therapeutic advantage of lowering elevated LDL-C levels are now well established (Gotto et al., Circulation 81, 1990, 17211733; Stein et al., Nutr. Metab. Cardiovasc. Dis. 2, 1992, 113-156; Illingworth, Med. Clin. North. Am. 84, 2000, 23-42). Cholesterol-rich, sometimes unstable, atherosclerotic plaques lead to the occlusion of blood vessels resulting in an ischemia or an infarct. Studies with respect to primary prophylaxis have shown that a lowering of plasma LDLC levels in plasma reduces the frequency of non-fatal incidences of CHD, while the overall morbidity remains unchanged. The lowering of plasma LDL-C levels in patients with pre-established CHD (secondary intervention) reduces CHD mortality and morbidity; meta-analysis of different studies shows that this decrease is proportional to the reduction of the LDL-C (Ross et al., Arch. Intern. Med. 159, 1999, 1793-1802). The clinical advantage of cholesterol lowering is greater for patients with pre-established CHD than for asymptomatic persons with hypercholesterolemia. According to current guidelines, cholesterol lowering treatment is recommended for patients who had survived a myocardial infarct or patients suffering from angina pectoris or another atherosclerotic disease, with a target LDL-C level of 100 mg/dl. Web site: http://www.delphion.com/details?pn=US06503907__ •

Medicine for the treatment of illnesses of the respiratory organs Inventor(s): Widauer; Josef O. (Allschwil, AT) Assignee(s): Medichemie AG (Ettingen, CH) Patent Number: 5,310,560 Date filed: May 5, 1992 Abstract: Chenodeoxycholic acid and ursodeoxycholic acid, both being natural gallic acids, are well known for the treatment of cholesterin gallstones, of biliaric dyspepsia, and also chronic liver diseases (only Urso). The object of the present invention is the use of these acids or a combination thereof for the making of a medicine for treating acute or chronic inflammatory illnesses of the respiratory organs. Excerpt(s): The present invention relates to the use of gallic acids chenodeoxycholic acid and ursodeoxycholic acid or a combination thereof for the manufacture of a medicine. Both gallic acids can be obtained in a part-synthetic process from cattle bile. It is known to administer the above-named gallic acids in daily doses between 5-20 mg/kg of body weight in order to dissolve cholesterin gallstones, and also for biliaric dyspepsia. The

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named gallic acids can be used either by themselves or in combination with one another. Because of somewhat differing effect mechanisms, they show an additive effect in a mixed preparation. Moreover, the ursodeoxycholic acid is also used in the treatment of reflux gastritis as well as in chronic hepatophatia. In connection with these known indications, reference is directed to Ulrich Leuschner: "Aktuelle Aspekte der Therapie mit Gallensauren", Deutsches Artzeblatt 86, Volume 48, C-2180-2186, November, 1989 or Alan F. Hofmann "Medical Dissolution of Gallstones by Oral Bile Acid Therapy", The American Journal of Surgery, Volume 158/Number 3, page 79-85, September 1989. Web site: http://www.delphion.com/details?pn=US05310560__ •

Method for treatment of cholelithiasis and chronic hepato- and cholecystopathies secondary to said disease Inventor(s): Ikayeva; Liliya V. (ulitsa Ogneva, 9, apt. 50, Vladikavkaz, SU) Assignee(s): none reported Patent Number: 5,320,601 Date filed: October 26, 1992 Abstract: The present invention relates to medicine.A method for treatment of cholelithiasis and chronic hepato- and cholecystopathies secondary to that disease consists in that the patient with concrements not in excess of 2 cm in size are instituted on the first day of treatment a diet which is not causative of deterioration of their general state, whereupon the patients' gastrointestinal tract is evacuated, a cholinolytic spasmolytic agent is administered, and tubage is performed, accompanied by oral administration of a vegetable oil; on the second day of treatment the patients are prescribed a meal of food which promotes a cholagogic effect, and abundant drink, whereupon the motor function of the intestine is stimulated until the concrements are eliminated. Excerpt(s): The present invention relates generally to medicine and more specifically to a method for treatment of cholelithiasis and chronic hepato- and cholecystopathies secondary to said disease. The invention can find application in gastroenterology for treatment of patients affected by cholelithiasis and exhibiting concrements sized up to 2 cm, as well as of those suffering from chronic noncalculous cholecystitis, cholecystopancreatitis, post-cholecystectomy and post-infectious hepatitis states, an incipient stage of hepatocirrhosis, and dyskinesias of the biliary tract. Cholelithiasis is a rather widespread disease accounted for by the formation of gallstones in the gall bladder and the biliary ducts. One state-of-the-art method for surgical treatment of cholelithiasis is known to be in extensive use nowadays, wherein the principal surgical interference is cholecystectomy, that is, ablation of the gall bladder. Such a surgical procedure may be combined with extraction of concrements from the biliary ducts followed by external or internal drainage of the common bile duct. Some other operative interventions may also be performed (cholecystectomy, cholecystostomy). Surgery on the gall bladder and biliary ducts requires definite indications in patients for a surgical interference and is far from ensuring steady convalescence (owing to the residual concrements that have remained unidentified). Web site: http://www.delphion.com/details?pn=US05320601__

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Method of dissolving cholesterol-rich calculi with short chain halogenated organic solvents and cosolvents Inventor(s): DeAntonio; Paul (Westminster, CA), Mayhan; Kenneth G. (Irvine, CA), Sorensen; John T. (Costa Mesa, CA) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 4,994,025 Date filed: August 29, 1989 Abstract: Disclosed is a method for dissolving cholesterol-rich calculi, most preferably gallstones in vivo, comprising contacting the calculus with a fluid compound of the formula R-X, R having 2 to 4 carbon atoms with substituents consisting of hydrogen of halogen, X being halogen, and wherein if X is fluorine, at least one substituent is selected from the group consisting of hydrogen, chlorine, bromine, or iodine. Usually R-X is 2bromo-2-chloro-1,1,1-trifluoroethane (also referred to as Halothane.) Other compounds of particular interest are 2-chloro-1,2,-dibromo-1,1,2-trifluoroethane, 1-bromo-2-chloro1,1,2-trifluoroethane, 2,3-dibromo-1,1,1-trifluoropropane, 2-iodo-1,1,1-trifluoroethane, 1,2-dichloro-1,1-difluoroethane, 1,1,2-trichloro-2,3,3-trifluorocyclobutane, hexafluoro1,1,3,4,-tetrachlorobutane, 1,1,1-trichlorotrifluoroethane, and 1,2-dibromotetrafluoroethane. Furthermore, Halothane and MtBE in combination effectively dissolve cholesterol-rich calculi.Finally, dissolution can be enhanced by adding to the dissolution solvent up to about 50 percent by volume of a lower alcohol. Usually the lower alcohol is ethanol in the amount of about 5 to 40, usually 10 to 30 and preferably about 10 percent by volume. Most preferably in this case, R-X is Halothane or 1,1,1trichlorotrifluoroethane. Dissolution using previously known solvents such as MtBE is also enhanced by such addition of lower alcohols. In addition, the practical use of MtBE for dissolution can be improved by the addition of the compounds described above as R-X, particularly Halothane, and usually at levels of about 5 to 50 volume percent Halothane. Excerpt(s): This invention relates to dissolution of cholesterol, in particular cholesterolrich calculi in vivo. Solidified deposits may develop in hollow organs or ducts within humans and animals and cause numerous health problems, as is known to those skilled in the art. Such deposits include cholesterol-rich gallstones. biliary duct stones in the biliary tract, and cholesterol plaque in the vascular system, for example. These deposits may be removed from the body in various ways, the most common being surgery, particularly in the case of gallstones. Gallstones are solidified deposits or calculi composed of cholesterol, bilirubin, bilirubin complexes and other components derived from bile. A majority of gallstones have a high cholesterol content distributed through their mass and therefore lend themselves to in vivo dissolution by introduction of a cholesterol dissolving solvent or cosolvent mixture into the area of the body where the calculi are located. In vivo dissolution avoids many of the hazards and complications of surgery, and so is desireable when it can be performed. It has been found to be advantageous, furthermore, to perform the dissolution by repeatedly oscillating or agitating the solvent around the calculi to enhance the dissolution rate. In addition, in the case of gallstones in the gallbladder, it is helpful to withdraw the immiscible bilesolvent mixture periodically in order to renew the cholesterol-bearing solvent and improve stone contact, thus enhancing the dissolution process. This dissolution process is described in U.S. Pat. No. 4,655,744, and apparatus for accomplishing it is described in U.S. Pat. No. 4,723,941, both of which are incorporated by reference fully herein. Web site: http://www.delphion.com/details?pn=US04994025__

Patents 89

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Method of treating and preventing gallstones Inventor(s): Krstulovic; Veljko J. (609 W. 114th St. Apt. 62, New York, NY 10025) Assignee(s): none reported Patent Number: 5,935,948 Date filed: April 7, 1998 Abstract: The present invention relates to a method of treating and/or preventing gallstones comprising administering a therapeutically effective amount of dehydrocholic acid. It is based, at least in part, on the discovery that consistent usage of dehydrocholic acid resulted in the dissolution of gallstones and prevention, elimination and/or amelioration of biliary colic in four subjects. Excerpt(s): The present invention relates to a method of preventing and/or treating gallstones, as well as elimination, amelioration, and/or prevention of biliary colic and diminishing or eliminating biliary colic comprising administering a therapeutic amount of dehydrocholic acid. Bile acids and their conjugates are essential components of bile. The physiological effects of bile acids as a whole include: induction of bile flow; feedback inhibition of bile acid synthesis; modulation of cholesterol synthesis; elimination of cholesterol (bile acids are water-soluble products of cholesterol metabolism and also solubilize cholesterol in bile and promote intestinal cholesterol excretion); and facilitation of dispersion and absorption of lipids and fat-soluble vitamins. Naturally occurring bile acids, accounting for 95 percent of biliary bile acids, include cholic acid, chenodeoxycholic acid, and deoxycholic acid; minor bile acids include lithocholic acid and ursodeoxycholic acid. Glycine and taurine conjugates of bile acids, known as bile salts, readily form micelles with and emulsify lipids in conjunction with biliary phospholipids. Web site: http://www.delphion.com/details?pn=US05935948__

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Method to remove common bile duct stones Inventor(s): Carroll; Brendon J. (2278 Betty La., Beverly Hills, CA 90210) Assignee(s): none reported Patent Number: 5,334,143 Date filed: April 17, 1992 Abstract: A catheter device and method for laparoscopically dilating the sphincter muscle to flush common bile duct stones into the duodenum is set forth where the catheter consists of a flexible tube having three lumens. An inflatable balloon is carried by the flexible tube at its distal end and is inflatable and deflatable through an insufflation port. Radiopaque markers placed distally and proximally of the balloon are used to visualize the location of the balloon flouroscopically. A guidewire is advanced through the cystic duct, common bile duct and into the duodenum over which the catheter is advanced and the balloon positioned at the juncture of the common bile duct and duodenum. The balloon is then inflated sufficiently to dilate the sphincter muscle; the balloon is then deflated and the common bile duct irrigated with a fluid injected through an irrigation port located proximally of the balloon to flush the gallstones from the common bile duct. Excerpt(s): This invention relates to an inflatable balloon catheter to be used during laparoscopic trans-cystic common bile duct exploration to dilate the sphincter muscle at

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the distal end of the common bile duct to allow stones to pass through the duct and into the duodenum. In the performance of cholecystectomy surgery a certain percentage of patients who undergo the operation will have gallstones that have migrated from their gallbladder to the common bile duct. The stones may spontaneously pass through the distal end of the bile duct into the duodenum causing no harm or they may be trapped in the common bile duct by the sphincter muscle at the distal end of the duct. In the event the sphincter muscle gets irritated by the stones, the muscle will trap them and prevent them from passing into the duodenum. The trapping of the stones backs up the common bile duct thereby causing jaundice, pancreatitis and cholangitis. Removal of the stones which had entered the common bile duct required that the surgeon make a large abdominal incision, remove the gallbladder, and then cut open the common bile duct. The surgeon would thereafter retrieve the stones one by one from the common bile duct by grasping the stones or using balloon catheters to pull them retrograde. Alternatively, the stones could be removed by resorting to endoscopic retrograde cholangiopancreatography-sphincterotomy (ERCP). Web site: http://www.delphion.com/details?pn=US05334143__ •

Multimodal displacement pump and dissolution system for saMen Inventor(s): Borsanyi; Alexander (Newport Beach, CA), Harp; Richard (La Costa, CA), Lebo; Robert (Silverado, CA), Pool; Scott L. (Santa Ana, CA), Rondinone; Joseph (Mission Viejo, CA), Sorensen; John T. (Costa Mesa, CA), Stone; Albert L. (Laguna Hills, CA), Wall; Roxanne (Newport Beach, CA) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 5,098,377 Date filed: July 26, 1990 Abstract: Disclosed is a pneumatically-driven volume controlled bellows pump apparatus for oscillating liquid into a localized area of the human body, preferably methyl-tertiary butyl ether or another solvent, into the gallbladder. The pump includes a fluid reservoir in the form of an inverted syringe attached via a stopcock to the bellows. The bellows is attached via a second stopcock to a catheter also attached to a priming syringe. An inlet pinch valve is disposed between the bellows and the fluid reservoir and an outlet pinch valve between the bellows and the fluid receiver.To use the pump, a pigtail catheter with outlets in the pigtail is inserted into the desired area of the body, preferably a receptacle such as the gallbladder, to introduce a selected volume of liquid for gallstone dissolution. Liquid is infused into the receptacle by decompression of the bellows with the inlet but not the outlet valve open and then by compression of the bellows with the outlet but not the inlet valve open. Repeated infusion and aspiration is automatically accomplished by decompression and compression of the bellows with the inlet valve closed and the outlet valve open, or by compression and decompression of the bellows while the inlet valve is open and the outlet valve is closed alternated with compression and decompression while the inlet valve is closed and the outlet valve is open. Complete aspiration is accomplished by the use of a vacuum pump attached to the fluid reservoir. Also disclosed are syringe units and a transfer cap for use with the pump, together with a method for dissolving gallstones. Excerpt(s): This invention relates to pumps, particularly pumps for introducing fluids into the human body, as well as syringes, bottle caps and the like for use in connection with such pumps for gallstone dissolution and the like. Solidified masses such as biliary duct stones and gallstones may develop in hollow organs or ducts within humans and

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animals and cause numerous health problems, as is known to those skilled in the art. These deposits may be removed from the body in various ways, including surgery or in vivo dissolution by solvents introduced into the localized area of the body, such as the gallbladder, where the stones are located. In order to effectively dissolve stones such as gallstones in vivo, however, an effective means of introducing and distributing the fluid is necessary; agitation of the fluid is advantageous and speeds up the dissolution process substantially; it can be accomplished by repeatedly cycling or oscillating the fluid into and out from the body area of interest. Furthermore, an effective dissolving agent is necessary; monooctanoin, for example, can be used, and methyl tertiary-butyl ether ("MTBE"), for example, has been found to be very effective, but is quite flammable. Moreover, while MTBE is non-toxic so long as it remains confined to the gallbladder, it is highly toxic if supplied in sufficient volume to cause leakage from the biliary duct into the surrounding tissues. Web site: http://www.delphion.com/details?pn=US05098377__ •

Shockwave source having a centrally disposed ultrasound locating system Inventor(s): Grasser; Franz (Eggolsheim, DE), Hassler; Dietrich (Uttenreuth, DE), Naser; Georg (Zirndorf, DE), Reichenberger; Helmut (Eckental, DE), Schmidt; Erhard (Erlangen, DE) Assignee(s): Siemens Aktiengesellschaft (Berlin and Munich, DE) Patent Number: 4,928,672 Date filed: June 23, 1988 Abstract: A shockwave source of the type wherein a shockwave is generated by rapid electromagnetic repulsion of a membrane by a rapidly energized coil has a central opening extending through the membrane and the coil. An ultrasound head of an ultrasound transmission and reception system is received in the opening. The ultrasound head is disposed in a mount which is rotatable around its longitudinal axis by a rotary drive. In one embodiment of the shockwave source, the shockwave source also has a focusing device disposed in front of the membrane, and in this embodiment the focusing device also has a central opening in which the ultrasound head is received. The ultrasound head has a distal end in contact with a liquid coupling agent for promoting transmission to, and reception from, a patient to which the shockwave source is coupled. The shockwave source is particularly suited for lithotripsy treatment of gallstones. Excerpt(s): The present invention is directed to a shockwave source for extracorporeal treatment of a calculus disposed in the body of a patient by disintegrating the calculus with shockwaves, and in particular to such a shockwave source operating on the principle of a rapid electromagnetic repulsion of a membrane to generate the shockwaves. Shockwave generators are generally known in the art of the type having a coil mounted within a coil carrier and an electrically conductive membrane spaced from and insulated from the coil. Generally a sack filled with a fluid coupling agent is provided at a side of the shockwave source intended to be applied to a patient, with shockwaves generated by the membrane traveling through the coupling agent to the patient upon rapid energization of the coil, and the subsequent rapid repulsion of the membrane therefrom. It is also generally known to make use of an ultrasound transmission and reception system combined with the shockwave generator to transmit an acoustic signal to the patient, and to receive echo signals from the patient, for locating and observing the calculus.

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Web site: http://www.delphion.com/details?pn=US04928672__ •

Therapeutic cholesterol gallstone dissolution method Inventor(s): Hofmann; Alan F. (La Jolla, CA), Schteingart; Claudio D. (La Jolla, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,212,202 Date filed: April 20, 1992 Abstract: A method and apparatus are disclosed for treating a patient having cholesterol calculi which involves infusing into the biliary tract of said patient a C.sub.5 -C.sub.6 ester having a boiling point in the range of 80.degree.-140.degree. C. in an amount and at a flow rate effective to at least partially dissolve said calculi rapidly. It is found that the ester has little or no tendency to accumulate in the blood stream when perfused into a patient, particular as compared to methyl t-butyl ether (MTBE), the solvent widely used at present. The invention also encompasses dissolving cholesterol calculi by exposing such calculi to contact with effective quantities of those solvent compounds. The method preferably uses a high flow rate catheter pumping system for infusing a gallstone dissolution solvent into the gallbladder of a patient and aspirating the gallstone dissolution solvent from the gallbladder, and a unit measure container of the solvent. The preferred esters are n-propyl acetate, isopropyl acetate, ethyl propionate and ethyl isobutyrate, with ethyl propionate being the most preferred. Contact flow rates are sufficiently high to insure fluid turbulence in the biliary tract region surrounding the calculi. Excerpt(s): The invention herein relates to medical treatments of cholesterol calculi (particularly gallstones) by contact dissolution with organic solvents. More particularly it relates to therapeutic methods using low viscosity non-toxic pumpable solvents. The contact dissolution of cholesterol gallstones by organic solvents in human patients is a well recognized medical procedure and may be favored over surgical procedures to remove gallstones in patients at increased risk of surgery; see, for instance, U.S. Pat. No. 4,205,086. The dissolution procedures normally involve infusion of the solvent into the biliary tract (including the gallbladder and the bile ducts) by means of a T-tube, nasobiliary tube, percutaneous transhepatic catheter or cholecystostomy tube by use of a constant infusion pump or by gravity or by manual repeated installation and withdrawal using a syringe; see Palmer, et al., Gut, 27, 2, 196 (1986). Often the stones fragment during the dissolution procedure, which advantageously increases the rate of dissolution. A number of different types of solvents have been used or suggested for the dissolution procedure. These include organic solvents such as diethyl ether, chloroform or d-limonene as well as aqueous micellar solutions of bile salts. The aforementioned U.S. Pat. No. 4,205,086 also lists a large number of useful liquid fatty acids and the alcohol esters thereof. A further solvent which has received substantial attention is monooctanoin, mentioned in U.S. Pat. No. 4,755,167 and several articles, such as Thistle, et al., Gastroenterology 78, 5, 1016 (1980). More recently a C.sub.5 ether, methyl t-butyl ether (MTBE) has been used as a cholesterol gallstone solvent; see, e.g., Allen, et al., Gastroenterology, 88, 1, 122 (1985); Thistle, et al., U.S. Pat. No. 4,758,596; and Thistle, et al., N. Engl. J. Med., 320, 633 (1989). Web site: http://www.delphion.com/details?pn=US05212202__

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Tool for laparoscopic surgery Inventor(s): Phillips; Edward H. (712 N. Roxbury Dr., Beverly Hills, CA 90210) Assignee(s): none reported Patent Number: 5,380,277 Date filed: November 2, 1993 Abstract: The invention relates to a instrument for laparoscopic surgery which permits the operating surgeon to irrigate or suction the operative area while performing electrocautery or laser hemostasis and dissection of body tissue with the same instrument.The invention also relates to a laparoscopic tool for evacuating free stones or blood clots from the operating area which are to large to be suctioned from the body cavity or to remove gallstones from a gallbladder which has been distended by stones and cannot be retrieved through an umbillical sheath. Excerpt(s): This invention relates to a tool for use in laparscopic surgery. Utilizing a high definition video monitor, a surgical team can perform operating techniques internal to the human body which are minimally invasive through the use of a laparoscope equipped with a television camera. The laparoscopic technique has been used to remove diseased gallbladders and stones by using a laser for hemostasis and disection of the gallbladder from the liver bed. Before the gallbladder is removed, the liver bed area is lavaged and irrigated, and suctioned. In order to irrigate or suction the liver bed area, the operating surgeon is required to temporarily abandon another instrument which he is manipulating when irrigation or fluid evacuation is desired. To avoid an increase in operating time which compromises the safety of the patient, an operating assistant is utilized to control the instrument which would otherwise be temporarily abandoned by the operating surgeon. Although the above discussion of the prior art was concerned with laparoscopic laser removal of the gallbladder, the identical procedure is used where the hemostasis and disection of the gallbladder from the liver bed is to be achieved by the use of electrocautery. Conventionally, after the gallbladder is freed from the liver, a grasping forcep is used to pull the gallbladder through an umbillical sheath. In the event of free gallstones or clots which are too large to be suctioned from the operative area, a grasping tool must be used to grasp such stones or clots which are then singularly removed from the body cavity or operating area. This procedure increases the time of the operation which increases the risk of the surgery. If there are stones in the gallbladder which are too large to come into the umbillical sheath, the gallbladder must be teased through the fascial opening after the sheath is pulled through the fascia. Should it not be possible for the gallbladder to be teased through the fascial opening, an incision must then be made which will then permit the gallbladder to be removed from the body. When there are numerous gallstones in the gallbladder, the stones will distend the lower portion of the gallbladder as the gallbladder is being teased through the fascial opening thereby forming an enlarged diametric cross-section which prevents removal of the gallbladder through the fascial opening. This again requires an incision to remove the gallbladder and further increases the risk of surgery. Web site: http://www.delphion.com/details?pn=US05380277__

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Use of endoscopic ultrasound and stimulated bilary drainage in the diagnosis of cholecystitis and microlithiasis Inventor(s): Berkhouse; Linda (Roanoke, VA), Dill; James E. (Goodview, VA) Assignee(s): Roanoke Gastroenterology, P.C. (Roanoke, VA) Patent Number: 5,495,851 Date filed: March 23, 1995 Abstract: The combined endoscopic ultrasound and stimulated biliary drainage method involves the following steps: inserting an endoscopic ultrasound device within the antrum of a stomach; positioning the endoscopic ultrasound device within the stomach such that the endoscopic ultrasound device is allowed to have a substantially unobstructed view of the gallbladder; activating the endoscopic ultrasound device such that it is capable of detecting whether the gallbladder exhibits any of the following: gallbladder sludge or small gallstones, focal wall thickening, or adhesions about the gallbladder and/or cystic duct; delivering a cholecystokinin analogue intravenously to the human to enable the gallbladder to contract and to produce an ejection fraction of bile from the gallbladder during each contraction thereof; determining the degree of contraction of the gallbladder by means of measuring each the ejection fraction of the gallbladder; and removing the ejection fractions from the patient and analyzing the ejection fractions to detect the presence or absence of calcium bilirubinate and/or cholesterol granules or crystals therein; whereby cholecystitis or microlithiasis of a gallbladder can be diagnosed with an accuracy or sensitivity of between about 90% to 98%. Excerpt(s): The present invention generally relates to a method which is capable of accurately diagnosing cholecystitis and microlithias. This method is particularly useful when conventional transabdominal ultrasound tests produce a negative result and the patient continues to suffer from right upper quadrant abdominal pain. In particular, the present invention combines endoscopic ultrasound and stimulated biliary drainage, utilizing an intravenously delivered CCK analogue or an intraluminally delivered magnesium sulfate, to diagnose cholecystitis and microlithias with an accuracy of up to about 98%. The diagnosis and at times the treatment of recurring right upper quadrant abdominal pain can be quite difficult. All physicians deal with patients having pain in this area and in whom the usual diagnostic tests are negative. The conditions that can cause right upper quadrant pain are multiple. A partial list includes cholecystitis, cholelithiasis (i.e., microlithias), irritable bowel syndrome, esophagitis, biliary dyskinesia and right lower lobe pneumonitis. Transabdominal ultrasound (TUS) has been considered the "gold standard" in the diagnosis of cholecystitis and choletithiasis until fairly recently. However, the diagnosis of cholecystitis and choletithiasis has proved difficult even when a transabdominal ultrasound instrument is used. As such, many patients experiencing recurring right upper quadrant abdominal pain due to cholecystitis or choletithiasis simple go undiagnosed and continue to explore other reasons for their discomfort. Web site: http://www.delphion.com/details?pn=US05495851__

Patents 95

Patent Applications on Gallstones 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 gallstones: •

Apparatus for performing diagnostic and therapeutic modalities in the biliary tree Inventor(s): Cotton, Peter B.; (Charleston, SC), Eddy, Bryan P.; (Broomfield, CO), Rowland, Christopher A.; (Marlborough, MA), Vergano, Michael G.; (Cumberland, RI) Correspondence: John E. Lynch; Fulbright & Jaworski L.L.P.; Market Square; 801 Pennsylvania Avenue, N.W.; Washington; DC; 20004-2623; US Patent Application Number: 20020193788 Date filed: August 16, 2002 Abstract: Catheter apparatus for performing diagnostic and therapeutic modalities in the biliary tree includes a catheter with multiple lumens. A first lumen is adapted to receive a guidewire and can serve as a transport lumen for contrast agent. A second lumen carries a cutting wire for performing a sphincterotomy. A third lumen can be used as an inflation lumen for a distally located balloon. Expansion of the balloon occludes a portion of the biliary tree and allows the catheter to sweep any gallstones through the sphincter of Oddi into the duodenum. Excerpt(s): This is a continuation application of our co-pending U.S. patent application Ser. No. 08/648,356 filed May 14, 1996 for an Apparatus for Performing Diagnostic and Therapeutic Modalities in the Biliary Tree that is a continuation of our U.S. patent application Ser. No. 08/242,168 filed May 13, 1994 for an Apparatus for Performing Diagnostic and Therapeutic Modalities in the Biliary Tree now U.S. Pat. No. 5,547,469 issued Aug. 20, 1996. This invention generally relates to apparatus that is useful in performing diagnostic and therapeutic modalities in the biliary tree and more particularly to apparatus that is adapted for facilitating the diagnosis of gallstones in the bile duct and other portions of the biliary tree and the removal of such gallstones. Historically the migration of gallstones into an individual's common bile duct was corrected by general surgical procedures. A surgeon would incise the bile duct and remove the gallstones and normally remove the gallbladder. In recent years less invasive treatment modalities have replaced these general surgical procedures and reduced patient trauma, long hospital stays and recovery periods. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Bile salt conjugates Inventor(s): Gilat, Tuvia; (Tel Aviv, IL) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20020091111 Date filed: February 21, 2002

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

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Abstract: The present invention relates to bile acid or bile salt fatty acid conjugates (hereinafter called "BAFAC), to their use in dissolving cholesterol gallstones in bile, preventing their occurrence or recurrence, to their use in reducing or preventing arteriosclerosis and to methods for the treatment of said diseases. The conjugates are of the formula W--X--G in which G is a bile acid or bile salt radical, W stands for one or two saturated fatty acid radicals and X is either a direct bond or a bonding member between bile acid or bile salt and the fatty acid(s). The conjugation is advantageously performed at a position selected among the 3, 6, 7, 12 and 24 positions of the bile acid or bile salt nucleus. The fatty acids are preferably saturated fatty acids having 6-26 carbon atoms. Excerpt(s): The present invention relates to bile acid or bile salt fatty acid conjugates (hereinafter called "BAFAC"), to their use in dissolving cholesterol gallstones in bile, preventing their occurrence of recurrence, to their use in reducing or preventing arteriosclerosis and to methods for the treatment of said diseases. It should be noticed that the terms bile acids and bile salts are similar and are used interchangeably. Gallstones are found in about 15% of people in most industrialized countries. Most gallstones are cholesterol gallstones, i.e. cholesterol being their main component. Thus, cholesterol gallstones represent a major health problem. Bile is often supersaturated with cholesterol which tends to crystallize. The prevention of cholesterol crystallization in bile will prevent the formation of cholesterol gallstones or their recurrence after procedures such as lithotripsy, dissolution, or stone extraction. The residence time of newly secreted bile in the gallbladder is short--less than 12-24 hours. The prevention of cholesterol crystallization in bile during such a period could prevent gallstone formation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Dihydroindole and tetrahydroquinoline derivatives Inventor(s): Ackermann, Jean; (Riehen, CH), Aebi, Johannes; (Basle, CH), Chucholowski, Alexander; (San Diego, CA), Dehmlow, Henrietta; (Grenzach-Wyhlen, DE), Morand, Olivier; (Hegenheim, FR), Panday, Narendra; (Basle, CH), Wallbaum, Sabine; (Ostfildern, DE), Weller, Thomas; (Binningen, CH) Correspondence: Hoffmann-la Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20030004156 Date filed: December 11, 2001 Abstract: The present invention relates to novel dihydroindole and tetrahydroquinoline derivatives and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes. Excerpt(s): The present invention is concerned with novel tetrahydroquinoline derivatives, their manufacture and their use oxidosqualene-lanosterol cyclase (EC 5.4.99.) is required for cholesterol, ergosterol and other sterols. Causal risk factors that development of coronary and peripheral atherosclerosis include

dihydroindole and as medicaments. 2,3the biosynthesis of directly promote the elevated low-density

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lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), hypertension, cigarette smoking and diabetes mellitus. Other synergistic risk factors include elevated concentrations of triglyceride (TG)-rich lipoproteins, small, dense lowdensity lipoprotein particles, lipoprotein (a) (Lp(a)), and homocysteine. Predisposing risk factors modify the causal or conditional risk factors and thus affect atherogenesis indirectly. The predisposing risk factors are obesity, physical inactivity, family history of premature CVD, and male sex. The strong connection between coronary heart disease (CHD) and high LDL-C levels in plasma, and the therapeutic advantage of lowering elevated LDL-C levels are now well established (Gotto et al., Circulation 81, 1990, 17211733; Stein et al., Nutr. Metab. Cardiovasc. Dis. 2, 1992, 113-156; Illingworth, Med. Clin. North. Am. 84, 2000, 23-42). Cholesterol-rich, sometimes unstable, atherosclerotic plaques lead to the occlusion of blood vessels resulting in an ischemia or an infarct. Studies with respect to primary prophylaxis have shown that a lowering of plasma LDLC levels in plasma reduces the frequency of non-fatal incidences of CHD, while the overall morbidity remains unchanged. The lowering of plasma LDL-C levels in patients with pre-established CHD (secondary intervention) reduces CHD mortality and morbidity; meta-analysis of different studies shows that this decrease is proportional to the reduction of the LDL-C (Ross et al., Arch. Intern. Med. 159, 1999, 1793-1802). The clinical advantage of cholesterol lowering is greater for patients with pre-established CHD than for asymptomatic persons with hypercholesterolemia. According to current guidelines, cholesterol lowering treatment is recommended for patients who had survived a myocardial infarct or patients suffering from angina pectoris or another atherosclerotic disease, with a target LDL-C level of 100 mg/dl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for identifying compounds to treat medical pathologies associated with molecular crystallization Inventor(s): Shell, John W.; (Hillsborough, CA) Correspondence: Reed & Associates; 800 Menlo Avenue; Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20020132758 Date filed: January 17, 2002 Abstract: Numerous diseases and disorders are caused or exacerbated by the formation of crystalline aggregates of a biomolecule that is normally in solution. Such diseases and disorders include cataracts, sickle cell anemia, atherosclerosis, kidney stones, gallstones, gout, and Alzheimer's disease. The present invention provides methods to identify compounds that can inhibit the adverse formation of crystalline aggregates, including fibrils, of a target biomolecule. These methods include the screening of large combinatorial libraries. The identified compounds are tested for their therapeutic utility in treating medical conditions caused or exacerbated by the adverse crystallization of biomolecules. Molecules that are slight modifications of the target biomolecule are found to be particularly effective in inhibiting the adverse crystallization, including fibril formation, of a target biomolecule. Excerpt(s): This application claims priority under 35 U.S.C.sctn.1 19(e)(1) to provisional U.S. Patent Application Serial No. 60/262,987, filed Jan. 18, 2001. This invention relates generally to inhibition of molecular crystallization processes associated with one or more medical pathologies, and more particularly relates to a method for screening compounds to identify potentially useful inhibitors of such crystallization processes.

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The invention additionally relates to a method of determining which, if any, of the identified potentially useful inhibitors are potentially useful as therapeutic agents by virtue of inhibiting a particular crystallization process. The invention also relates to a method for treating ocular cataracts by inhibiting the crystallization of one or more lenticular proteins. Crystalline materials consist of atoms that are regularly ordered in a periodically repeating pattern. At thermodynamic equilibrium, a crystal forms in preference to other possible phases when the total energy of the crystal is less than that of the phase (generally a fluid) from which the crystal grows. Crystals preferentially form because the crystalline phase has lower total energy than that of less-ordered phases, such as amorphous or glassy materials. The Second Law of Thermodynamics, however, requires permissible chemical reactions (including phase changes such as crystallization) to increase the total entropy (disorder) of the universe. Since a crystal is structurally more ordered than the fluid from which is grows, crystallization must proceed by creating a net entropy increase in the environment; this is accomplished by a release of heat (which increases disorder) into the surroundings. The formation of a crystal also requires that more heat be released (entropy increased) by crystallization than by the formation of a glassy or amorphous (non-crystalline) phase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods fo treating conditions associated with insulin resistance with aicar, (5amino-4-imidazole carboxamide riboside) and related compounds Inventor(s): Ido, Yasuo; (Brookline, MA), Kraegen, Edward W; (Sydney, AU), Ruderman, Neil; (Newton, MA) Correspondence: Weingarten, Schurgin, Gagnebin & Lebovici Llp; Ten Post Office Square; Boston; MA; 02109; US Patent Application Number: 20030212014 Date filed: March 12, 2003 Abstract: The long-term usage of AICR (5-aminio, 4-imidazole carboxamide riboside) to produce sustained metabolic and biological changes in mammals that overcome insulin resistance, i.e., increase insulin sensitivity, and result in benefits in diseases and conditions such as diabetes, hypertension, atherosclerosis, polycystic ovary syndrome and gallstones is described long-term usage of AICAR, particularly intermittent administration, e.g., three days per week, appears to have some of the positive effects of exercise, having an impact on the amount Of food consumed by a subject and resulting in reduced fat build-up and increase in muscle mass. Therefore, AICAR administration has a positive impact in reducing obesity. AICAR can also Prove useful in preventing or treating vascular diseases associated with hyperglycemia, high plasma levels of free fatty acids (FFA) and triglyceride, and insulin resistance by virtue of the fact that this agent activates fatty acid oxidation. Animal tests have Shown that chronic intermittent treatment with AICAR has not resulted in any noticeable toxic effects. AICAR and related compounds are activators of AMP-activated protein kinase (AMPK) and, furthermore, are effective at decreasing malonyl CoA levels in the animal. Excerpt(s): This application claims the priority of the following applications: U.S. Provisional Application No. 60/222,131, filed Jul. 31, 2000 entitled, USE OF AICAR (5AMINO-4-IMIDAZOLE CARBOXAMIDE RIBOSIDE) AND RELATED COMPOUNDS TO TREAT INSULIN RESISTANCE; International Application No. PCT/US00/40607, filed Aug. 9, 2000 entitled, METHOD OF MAINTAINING VASCULAR INTEGRITY USING AICAR (5-AMINO-4-IMIDAZOLE CARBOXAMIDE RIBOSIDE) AND

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RELATED COMPOUNDS; and International Application No. PCT/US01/18467 filed Jun. 6, 2001 entitled, USE OF AICAR (5-AMINO-4-IMIDAZOLE CARBOXAMIDE RIBOSIDE) AND RELATED COMPOUNDS FOR THE PREVENTION AND TREATMENT OF OBESITY, the whole of which are hereby incorporated by reference herein. AMP-activated protein kinase (AMPK) is a cytoplasmic enzyme that has been shown to exist in both the liver and skeletal muscle. As its name indicates, AMPK is activated by increasing levels of AMP and, secondarily, by an increase in the ratio of AMP to ATP in the cell. AMP levels rise in the cell as ATP is hydrolyzed to ADP and Pi. Two molecules of ADP, through the action of myokinase, also known as adenylate kinase, produce one molecule of ATP and one molecule of AMP. In addition to its activation by AMP, AMPK is activated through phosphorylation by an upstream kinase called AMPK kinase (AMPKK). AMP also allosterically activates AMPKK. Phosphorylation of AMPK by AMPKK makes it a poor substrate for phosphatases. All these factors combined together make AMPK very sensitive to minimal fluctuations in cellular AMP levels. AMPK has several known substrates, specifically enzymes that it can phosphorylate and modulate. In the liver, AMPK has been shown to phosphorylate hydroxymethyl glutaryl CoA (HMGCOA) reductase and acetyl CoA carboxylase (ACC), inhibiting the actions of both enzymes. Reducing HMGCOA reductase activity inhibits cholesterol synthesis, and reducing ACC activity decreases the generation of malonyl CoA, an intermediate in fatty acid synthesis. In skeletal muscle, AMPK also is an inhibitor of carnitine palmitoyl transferase I, which regulates the uptake of fatty acids into mitochondria where they are oxidized. In addition, AMPK has been shown to increase glucose transport into the muscle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel anticholesterol compositions and method for using saMen Inventor(s): Dudley, Robert; (Kenilworth, IL), Liao, Shutsung; (US), Song, Ching; (Chicago, IL) Correspondence: Christine M. Rebman; Mayer Brown Rowe & Maw; P.O. Box 2828; Chicago; IL; 60690-2828; US Patent Application Number: 20030153541 Date filed: June 19, 2002 Abstract: Compositions, methods, combinations, and kits for treating a disorder related to elevated serum cholesterol concentration, for example, atherosclerosis, elevated LDL plasma levels, low HDL plasma levels, hypertriglyceridemia, hyperlipidemia, hypertension, hypercholesterolemia, cholesterol gallstones, lipid storage diseases, obesity, and diabetes. The compositions, methods, combinations, and kits of the present invention are pharmaceutical compositions comprising at least two of an LXR receptor modulator, a therapeutically effective amount of a catechin, and/or a therapeutically effective amount of a lipid regulating agent, such as a HMG-CoA reductase inhibitor, a fibric acid derivative, niacin, a bile-acid sequestrant, an absorption inhibitor, probucol, raloxifene and its derivatives, an azetidinone compound, and an unsaturated omega-3 fatty acid. Excerpt(s): Pursuant to 35 U.S.C.sctn.sctn. 119(e) and 120, this application claims the benefit of U.S. application Ser. No. 09/530,433, filed Apr. 28, 2000, which is the National Stage filing of PCT/US98/23041, filed Oct. 30, 1998, which claims priority to prior U.S. provisional application No. 60/063,770, filed Oct. 31, 1997; U.S. application Ser. No. 09/560,236, filed Apr. 28, 2000, which claims priority to prior U.S. provisional

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application No. 60/131,728, filed Apr. 30, 1999; U.S. application Ser. No. 10/072,128 filed on Feb. 8, 2002, which claims priority to U.S. provisional application No. 60/267,493, filed Feb. 8, 2001; U.S. application Ser. No. 10/137,695 filed May 2, 2002, which claims priority to U.S. provisional application No. 60/288,643, filed May 3, 2001; and prior U.S. provisional application No. 60/348,020, filed Nov. 8, 2001, the disclosure of which are incorporated herein by reference. The present invention relates generally to compositions and methods for treating a disorder related to elevated serum cholesterol concentration. It has been well known that high cholesterol concentration is related to vascular disorders such as coronary heart disease or atherosclerosis. See, e.g., Essays of an Information Scientist, 1986, 9, 282-292; and "Cholesterol", Microsoft.RTM. Encarta.RTM. Encyclopedia 2000. It has also been found that some neurodegenerative diseases such as elevated senile cognitive impairment or dementia (e.g., Alzheimer's disease) can be attributed to an elevated concentration of cholesterol, as well. See, e.g., Sparks, D. L. et al., Microsc. Res. Tech., 2000, 50, 287-290. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Reverse Inventor(s): Rudder, Belinda Jean; (Roosevelt, NY), Rudder, Ebony Shanee; (Roosevelt, NY), Rudder, Erton Wendell JR.; (Roosevelt, NY) Correspondence: Belinda Rudden; 256 Lincoln AVE.; Roosevelt; NY; 11575; US Patent Application Number: 20030072815 Date filed: October 12, 2001 Abstract: A injection dosage form containing pure peanut oil in controlling disorders that arise in cells, or correct errors in the genetic code that cause mental, and physical disorders also in the process Mitosis cells divide, or forms identical cells, restore cells hereditary material that's scattered throughout the nucleus, restore aging, DNA restore torn tissue, muscle, alter the code and erase hundreds of inherited mental, and physical aids, deadly diseases, by enlarge cells, asthma, heart problems, child bearing, enlarge nose, lip, breast, penis, ear lobe, hearing, lungs, veins, gallstones, alter mature nerve cells, reproduce, or replace damage, or destroyed cells, replace worn out, or disease tissue, muscles, heart, cataracts, a stump of an amputated limb to re-grow. This will change the hereditary process of humans with diseases. These disorders are provided in an acceptable form. The dosage form comprises pure peanut oil which is applies in an amount that provides for a relatively period during which the composition is being excepted by a patient, but which allows substantially immediate release of the pure peanut oil after the composition has been injected. This will correct diseases that result from foreign invader organisms call pathogens, also that threaten our homeostasisidentified molecules or outer surfaces the membrane.The development of DNA technology and a good function gene can be inserted into the cells of a patient, and can correct genetic defects, also give new function to the cell. This is the way type of viruses attack humans cells. The adjacent tissue this cell is the basic building block fundamental unit of the body chromosomes of cell membranes and the nucleus, cytoplasm within the cell membrane and the nucleus holds the genetic material chromosomes this will cure all defects, disorders, diseases of all kind, like cataracts and cancer. Excerpt(s): It is an object that is from the plant that grows peanuts. That improves method of enlarging cells. Pure peanut oil. It is a further object of the invention to provide an improved method for rapidly delivering injections to the adjacent tissues basic building block fundamental unit, chromosomes of cell membrane, cytoplasm. It is

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further object of the invention within the cell membrane, nucleus holds the genetic material chromosomes, and homeostasis identified molecules or outer surfaces the membrane. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Substituted 4-phenyltetrahydroisoquinolinium salts, process for their preparation, their use as a medicament, and medicament containing them Inventor(s): Bleich, Markus; (Hunfelden-Dauborn, DE), Heinelt, Uwe; (Wiesbaden, DE), Hofmeister, Armin; (Oppenheim, DE), Lang, Hans-Jochen; (Hofheim, DE), Wirth, Klaus; (Kriftel, DE) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030171580 Date filed: December 20, 2002 Abstract: The invention relates to novel compounds of the formula I 1in which R1 to R10 R7 are as defined herein. In one embodiment, these compounds may be used as antihypertensives, for reducing or preventing ischemia-induced damage, as medicaments for surgical intervention for the treatment of ischemias of the nervous system, of stroke and of cerebral edema, of shock, of impaired respiratory drive, for the treatment of snoring, as laxative, as agent against ectoparasites, to prevent the formation of gallstones, as antiatherosclerotics, agents against late complications of diabetes, cancers, fibrotic disorders, endothelial dysfunction, organ hypertrophies and hyperplasias. In another embodiment, the compounds may be inhibitors of the cellular sodium-proton antiporter and influence serum lipoproteins and thus be used for the treatment of atherosclerotic lesions. Excerpt(s): This application claims the benefit of foreign priority under 35 U.S.C.sctn.119 of German patent application no. 10163914.7, filed on Dec. 22, 2001 and the contents of which are incorporated by reference herein. This application also claims the benefit of priority of U.S. Provisional Application No. 60/353,614, filed Feb. 1, 2002, the contents of which are incorporated by reference herein. and their pharmaceutically acceptable salts, and the trifluoroacetic acid salts. and the pharmaceutically acceptable salts and trifluoroacetates thereof. 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 gallstones, 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 “gallstones” (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 gallstones.

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

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CHAPTER 6. BOOKS ON GALLSTONES Overview This chapter provides bibliographic book references relating to gallstones. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on gallstones 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 “gallstones” (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 gallstones: •

Indigestion: Living Better with Upper Intestinal Problems from Heartburn to Ulcers and Gallstones Source: New York, NY: Oxford University Press. 1992. 227 p. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $11.95 plus shipping and handling. ISBN: 019508554X. Summary: This book offers advice on how to take care of and avoid a whole complex of disturbances categorized as indigestion. The author begins with an overview of the anatomy and physiology of digestion, including a chapter on terminology and definitions. After an additional chapter on diagnostic testing, the author turns to specific problems, including acid related problems (heartburn, esophagitis, and hiatal hernia), peptic ulcers, nonulcer dyspepsia, chest pain, gallbladder problems and gallstones, pancreatic diseases, jaundice, malabsorption and maldigestion, food intolerance and

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food allergies, the impact of aging on the upper digestive tract (including the role of medications and drug interactions), and the brain gut connection. The appendices of the book offer coverage of related problems, including belching, nausea and vomiting, dry mouth and bitter taste, difficulty in tasting, lump in the throat, butterflies, difficulties in swallowing, delayed stomach emptying, the effects of diabetes on the upper digestive system, and the controversy over yeast. The author hopes to foster a cooperative dialogue between patients and their physicians as they work together to diagnose and manage upper digestive tract problems. A subject index concludes the book. 8 figures. 6 tables.

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

Advances in Gastroenterology: 9. Gallstone Disease in the Elderly by Di Mario (2000); ISBN: 8829912727; http://www.amazon.com/exec/obidos/ASIN/8829912727/icongroupinterna

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Bile Acids and the Liver: With an Update on Gallstone Disease (Falk Symposium, Vol 42) by G. Paumgartner, et al (1988); ISBN: 0852006756; http://www.amazon.com/exec/obidos/ASIN/0852006756/icongroupinterna

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Bile Acids in Health and Disease: Update on Cholesterol, Gallstones and Bile Acid Diarrhea by Riadh Jazrawi, et al (1988); ISBN: 0746200765; http://www.amazon.com/exec/obidos/ASIN/0746200765/icongroupinterna

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Bile Acids, Cholestasis, Gallstones: Advances in Basic and Clinical Bile Acid Research: Proceedings of the Falk Symposium No. 84, Held in Berlin (Falk Symposium, Vol 84) by Germany)/ Leuschner, U./ Fromm, Hans Falk Symposium 1995 Berlin, Hans Fromm (1996); ISBN: 0792388933; http://www.amazon.com/exec/obidos/ASIN/0792388933/icongroupinterna

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Bile, Bile Acids, Gallstones, and Gallstone Dissolution by Alan F. Hofmann; ISBN: 0852004974; http://www.amazon.com/exec/obidos/ASIN/0852004974/icongroupinterna

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Chenodeoxycholic Acid and Gallstone Dissolution: A Bibliography of Relevant Articles, Abstracts, and Editorials by A.F. Hofmann; ISBN: 0852002203; http://www.amazon.com/exec/obidos/ASIN/0852002203/icongroupinterna

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Cholelithiasis: Causes and Treatment by Fumio, Md. Nakayama (1999); ISBN: 0896403343; http://www.amazon.com/exec/obidos/ASIN/0896403343/icongroupinterna

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Coping With Gallstones by Joan Gomez; ISBN: 0859698378; http://www.amazon.com/exec/obidos/ASIN/0859698378/icongroupinterna

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Dieting and gallstones (SuDoc HE 20.3323:G 13) by U.S. Dept of Health and Human Services; ISBN: B00010YG4U; http://www.amazon.com/exec/obidos/ASIN/B00010YG4U/icongroupinterna

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Epidemiology and Prevention of Gallstone Disease by L. Capocaccia, et al (1984); ISBN: 0852008503; http://www.amazon.com/exec/obidos/ASIN/0852008503/icongroupinterna

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Gallstone Disease and Its Management by Malcolm C. Bateson (1987); ISBN: 0852009798; http://www.amazon.com/exec/obidos/ASIN/0852009798/icongroupinterna

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Gallstone Disease: Pathophysiology and Therapeutic Approaches by W. Swobodnik, et al (1990); ISBN: 0387509658; http://www.amazon.com/exec/obidos/ASIN/0387509658/icongroupinterna

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Gallstones; ISBN: 0306401797; http://www.amazon.com/exec/obidos/ASIN/0306401797/icongroupinterna

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Gallstones by Keith Murdoch; ISBN: 0720500095; http://www.amazon.com/exec/obidos/ASIN/0720500095/icongroupinterna

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Gallstones & Their Treatment: A Guide of Patients (Surgical Series) by James Norman, et al (1995); ISBN: 1885274211; http://www.amazon.com/exec/obidos/ASIN/1885274211/icongroupinterna

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Gallstones (Contemporary Issues in Gastroenterology, Vol 4) by Sidney Cohen, Soloway (Editor); ISBN: 044308369X; http://www.amazon.com/exec/obidos/ASIN/044308369X/icongroupinterna

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Gallstones : discussions in surgical management; ISBN: 0874889537; http://www.amazon.com/exec/obidos/ASIN/0874889537/icongroupinterna

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Gallstones and laparoscopic cholecystectomy (SuDoc HE 20.3046:10/3) by U.S. Dept of Health and Human Services; ISBN: B00010FE9G; http://www.amazon.com/exec/obidos/ASIN/B00010FE9G/icongroupinterna

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Gallstones and laparoscopic cholecystectomy : Janaury 1989 through August 1992 : 683 citations (SuDoc HE 20.3615/2:92-4) by Peggie S. Tillman; ISBN: B00010BAQM; http://www.amazon.com/exec/obidos/ASIN/B00010BAQM/icongroupinterna

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Gallstones and Liver Disease (The BMA Family Doctor Guides) by Malcolm Bateson; ISBN: 1853360775; http://www.amazon.com/exec/obidos/ASIN/1853360775/icongroupinterna

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Hepatobiliary Diseases: Cholestasis and Gallstone (Falk Symposium, Vol 17A) by M. Acalovschi (Editor), G. Paumgartner (Editor) (2001); ISBN: 0792387708; http://www.amazon.com/exec/obidos/ASIN/0792387708/icongroupinterna

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Indigestion: Living Better With Upper Intestinal Problems from Heartburn to Ulcers and Gallstones by Henry D. Janowitz (1992); ISBN: 0195063082; http://www.amazon.com/exec/obidos/ASIN/0195063082/icongroupinterna

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Lithotripsy and Related Techniques for Gallstone Treatment by H. Joachim Burhenne; ISBN: 0815113757; http://www.amazon.com/exec/obidos/ASIN/0815113757/icongroupinterna

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Lithotripsy and Related Techniques for Gallstone Treatment: Adapted from the Proceedings of the Third International Symposium on Biliary Lithotripsy, Munich, Germany, September 13-15, 1990 by Germany)/ Sauerbruch, Tilman International

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Symposium on Biliary Lithotripsy 1990 Munich, et al; ISBN: 0815166249; http://www.amazon.com/exec/obidos/ASIN/0815166249/icongroupinterna •

Liver Disease and Gallstones by Alan G. Johnson; ISBN: 019261505X; http://www.amazon.com/exec/obidos/ASIN/019261505X/icongroupinterna

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Recent Advances in the Epidemiology and Prevention of Gallstone Disease: Proceedings of the 2nd International Workshop on Epidemiology and Preventio (Developments in Gastroenterology, 12.) by International Workshop on the Epidemiology and Prevention of Gallstone, et al (1991); ISBN: 0792309944; http://www.amazon.com/exec/obidos/ASIN/0792309944/icongroupinterna

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Techniques in the Management of Gallstone Disease by Ara Darzi (Editor), et al; ISBN: 0632036753; http://www.amazon.com/exec/obidos/ASIN/0632036753/icongroupinterna

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The 2002 Official Patient's Sourcebook on Gallstones: A Revised and Updated Directory for the Internet Age by James N., Md. Parker (Editor), et al (2002); ISBN: 0597832765; http://www.amazon.com/exec/obidos/ASIN/0597832765/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “gallstones” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Chenodeoxycholic acid therapy of gallstones. Workshop held in Freidburg i. Br., October 1973. Editors: A. F. Hofmann [and] G. Paumgartner. Author: Paumgartner, G. (Gustav); Year: 1974; Stuttgart, New York, Schattauer, 1974; ISBN: 3794504119

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Gallstones and ghosts [by] Hubert Bagster [pseud.]. Author: Trumper, Hubert Bagster.; Year: 1958; New York, Simon and Schuster, 1958

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Gallstones and laparoscopic cholecystectomy: January 1989 through August 1992: 683 citations Author: Tillman, Peggie S.; Year: 1992; Bethesda, Md.: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of Medicine, Reference Section; Washington, D.C.: Sold by the Supt. of Docs., U.S. G.P.O., 1992

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Gallstones; causes and treatment. Author: Rains, A. J. Harding (Anthony John Harding); Year: 1964; London, Heinemenn [1964]

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Introduction to the differential diagnosis of the separate forms of gallstone disease , based upon his own experience gained in 433 laparotomies for gallstones, by

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

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Professor Hans Kehr. Authorized translation by William Wotkyns Seymour. with an introduction by Prof. Kehr. Author: Kehr, Hans,; Year: 1901; Philadelphia, P. Blakiston's son; co., 1901 •

Studies on the etiology of gallstones; a subtilis-like bacilli-group as an etiologic factor, by Karl Mårtensson. Author: Mårtensson, Karl.; Year: 1941; [Stockholm] Nordisk rotogravyr [1941]

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

Gallstone Disease and Its Complications Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1065-1090. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Gallbladder removal (cholecystectomy) is the most common elective abdominal operation in the United States and is overwhelmingly necessitated by the presence of gallstones. This chapter on gallstone disease and its complications is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include epidemiology, risk factors, pathogenesis, and natural history of gallstones (cholelithiasis); and clinical manifestations of gallstone disease, including imaging studies of the biliary tract, biliary colic and chronic cholecystitis, acute cholecystitis, choledocholithiasis (bile duct stones), cholangitis (bacterial cholangitis), and uncommon complications of gallstone disease. The chapter includes a mini-outline with page citations, full-color illustrations, and extensive references. 5 figures. 5 tables. 201 references.

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Gallstone Disease Source: in Beckingham, I.J., ed. ABC of Liver, Pancreas and Gallbladder. London, UK: BMJ Publishing Group. 2001. p.5-8. 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. ISBN: 0727915312. Summary: Gallstones are the most common abdominal reason for admission to the hospital in developed countries and they account for an important part of healthcare expenditures. This chapter on gallstone disease is from an atlas of the liver, pancreas

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and gallbladder. Topics covered include the types of gallstones and their etiology; the clinical presentation of gallstone problems, including biliary colic or chronic cholecystitis, acute cholecystitis, jaundice, acute cholangitis, acute pancreatitis, and gallstone ileus; the natural course of gallstone disease; the management of gallstone disease, including cholecystectomy (removal of the gallbladder) and alternative treatments; and the management of common bile duct stones. The author notes that laparoscopic cholecystectomy has become the treatment of choice for gallbladder stones, with an accompanying risk of bile duct injury of approximately 0.2 percent. Asymptomatic gallstones do not require treatment. The chapter concludes with summary points of the concepts discussed. 10 figures. 5 tables. •

Gallstone Disease: Surgical Treatment 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. 260270. 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: Surgical therapy for gallstones can be associated with morbidity (illness) and mortality (death). This fact has led to debate on the use of surgery, especially in asymptomatic and mildly symptomatic patients. This chapter on the surgical treatment of gallstone disease 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 the controversy has been further complicated by the introduction of laparoscopic cholecystectomy, with its touted benefits of decreased morbidity and improved recovery times. The authors discuss the evidence concerning the benefits and risks of surgical therapy for gallstone disease (cholelithiasis) and its complications. Considering the current evidence, expectant management rather than prophylactic cholecystectomy (removal of the gallbladder) is indicated for the typical patient with asymptomatic gallstones. However, certain populations who are more at risk for complications of gallstone disease (such as people with diabetes) need to be considered separately. Patients with uncomplicated biliary colic (pain arising from gallstones) should be offered surgery as an option to controlling symptoms. Patients with complications of cholelithiasis (gallstones) should have surgery to prevent future complications. Considering the current evidence, in the elective setting, laparoscopic cholecystectomy appears to be as safe as open cholecystectomy and provides a short term improvement in quality of life. There is a lack of convincing evidence of its touted beneficial effect on length of stay or recovery time (and thus possibly economic benefit). The authors also briefly consider therapy for gallstone pancreatitis and choledocholithiasis (common bile duct stones). 4 tables. 58 references.

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Cholelithiasis and Cholecystitis Source: in Friedman, L.S. and Keeffe, E.B., eds. Handbook of Liver Disease. Philadelphia, PA: Churchill-Livingstone. 1998. p. 449-463. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. Email: [email protected]. PRICE: $73.00 plus shipping and handling. ISBN: 0443055203.

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Summary: This chapter on cholelithiasis (gallstones) and cholecystitis (gallbladder infection) is from a comprehensive handbook in outline format that offers easy access to information on the full range of liver disorders and covers symptoms, signs, differential diagnoses, and treatments. There are two main types of gallstones: cholesterol and pigment. Pigment gallstones are further subdivided into black and brown varieties. The pathogenesis of cholesterol and pigment stones is different, but the clinical syndromes they cause are similar. Most gallbladder stones are asymptomatic. When they become symptomatic, biliary pain is the most common manifestation. Hallmarks of biliary pain are its episodic nature and location in the upper abdomen, usually in the right upper quadrant. Other conditions may coexist with gallstones and account for symptoms attributed initially to the stones. The treatment of choice for symptomatic gallbladder stones is laparoscopic cholecystectomy; when this approach is not feasible, open cholecystectomy is the alternative. Acute cholecystitis is the most common complication of gallstones and cholecystectomy is the treatment of choice. Consultation among the internist, gastroenterologist, surgeon, and radiologist is frequently warranted in order to arrive at the most efficient plan for care. Acute acalculous cholecystitis requires a high index of suspicion for diagnosis; patients are usually quite ill, and rapid therapy is necessary. 10 references. •

Gallstone Management in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 317-320. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on gallstone (cholelithiasis) management in inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and Ulcerative Colitis (UC), together known as IBD. The association between IBD and hepatobiliary (liver, gallstone, bile ducts) disorders has been well established. Both CD and chronic Ulcerative Colitis (UC) can affect the liver and biliary system. Indeed, hepatobiliary involvement in patients with IBD varies from the asymptomatic state to the development of symptomatic complications related to chronic liver injury. Gallstones represent one of the most frequently encountered clinical hepatobiliary problems in patients with IBD especially those with Crohn's disease. In this chapter, the authors present an overview of the management of gallbladder stones and biliary sludge in patients with IBD. A summary of the epidemiology and pathogenesis of gallstones and biliary sludge in these patients is provided to guide therapeutic decisionmaking, which should aim not only to address symptomatic stones but also to prevent their development. Precipitating factors or conditions including prolonged fasting, total parenteral nutrition (TPN), and use of the drugs ceftriazone or octreotide must be avoided. Patients with symptomatic sludge or complications should have cholecystectomy (removal of the gallbladder). In poor surgical candidates, alternative interventions include oral agents for bile acid dissolution and percutaneous cholecystostomy. 1 figure. 1 table. 8 references.

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Gallstones and Inflammatory Gallbladder Diseases Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.597-628.

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Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on gallstones and inflammatory gallbladder diseases is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers the composition of gallstones and of bile; factors in cholesterol gallstone formation; pigment gallstones; radiology of gallstones; the natural history of gallstones, including silent gallstones; treatment of gallstones in the gallbladder, with cholecystectomy or laparoscopic cholecystectomy; non-surgical treatment of gallstones in the gallbladders, including dissolution therapy, direct solvent dissolution, and shock-wave therapy; and percutaneous cholecystolithotomy; acute cholecystitis; empyema of the gallbladder; perforation of the gallbladder; emphysematous cholecystitis; chronic calculous cholecystitis; acalculous cholecystitis, including acute, chronic, typhoid cholecystitis and acute cholecystitis in AIDS; other gallbladder pathology, including cholesterolosis of the gallbladder, xanthogranulomatous cholecystitis, adenomyomatosis, and porcelain gallbladder; postcholecystectomy problems; sphincter of Oddi dysfunction; gallstones in the common bile duct (choledocholithiasis); management of common duct stones, including acute obstructive suppurative cholangitis and acute cholangitis; common duct stones without cholangitis, including patients with gallbladder in situ, acute gallstone pancreatitis, large common duct stones, trans T-tube tract removal of stones, intra-hepatic gallstones, and Mirizzi's syndrome; biliary fistulae, external and internal; gallstone ileus; hemobilia; bile peritonitis; and the association of gallstones with other diseases, including colorectal and other cancers, and diabetes mellitus. 16 figures. 4 tables. 206 references. •

Liver Metabolism, Physiology of Bile Formation, and Gallstones Source: in Rose, S. Gastrointestinal and Hepatobiliary Pathophysiology. Malden, MA: Blackwell Science, Inc. 1998. p. 123-134. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781) 388-8250. Fax (781) 388-8270. E-mail: [email protected]. Website: www.blackwellscience. PRICE: $26.00 plus shipping and handling. Summary: This chapter on liver metabolism, physiology of bile formation, and gallstones is from a textbook that focuses on the pathophysiologic basis of gastrointestinal and hepatobiliary (liver and biliary tract) diseases while encouraging an integrative, problem-solving approach. The chapter begins with a list of learning objectives and an illustrative case study, then covers the pathways of carbohydrate, amino acid, and ammonia metabolism; fat and cholesterol metabolism; the role of the liver in protein synthesis and degradation; detoxification mechanisms of the liver; the role of the liver in hormone metabolism; pathways of fat, cholesterol, and bile acid metabolism; the origins, major components, and functions of bile; the mechanisms of bile secretion; the role of the enterohepatic circulation; the anatomy and physiology of the biliary tract; and the factors involved in gallstone formation. The chapter concludes with a follow up to the case study, a list of review questions, and the answers to the review questions, with brief explanations. 5 figures. 3 tables.

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Nonsurgical Treatment of Gallstones Source: in Danzi, J.T.; Scopelliti, J.A., eds. Office Management of Digestive Diseases. Malvern, PA: Lea and Febiger. 1992. p. 112-118.

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Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This chapter, from a medical textbook about the office management of common gastrointestinal diseases, discusses the nonsurgical treatment of gallstones. Topics include clinical manifestations of gallstones, taking the family history and performing the physical examination, the pathogenesis of cholesterol gallstones and of pigment gallstones, oral dissolution therapy, contact dissolution therapy, and extracorporeal shock wave lithotripsy. 8 references.

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CHAPTER 7. MULTIMEDIA ON GALLSTONES Overview In this chapter, we show you how to keep current on multimedia sources of information on gallstones. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

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

Goodbye Gallstones Source: Madison, WI: University of Wisconsin Hospitals and Clinics, Department of Outreach Education. 1995. (videocassette). Contact: Available from University of Wisconsin Hospital and Clinics. Picture of Health, 702 North Blackhawk Avenue, Suite 215, Madison, WI 53705-3357. (800) 757-4354 or (608) 263-6510. Fax (608) 262-7172. PRICE: $19.95 plus shipping and handling; bulk copies available. Order number 020195A. Summary: More than one million people will discover they have gallstones this year, and most will be women. Not all gallstones cause problems, but when they do, a variety of treatments are available. This videotape is one in a series of health promotion programs called 'Picture of Health,' produced by the University of Wisconsin. In this program, moderated by Mary Lee and featuring Dr. Eberhard Mack, the common symptoms, diagnosis, and management of gallstones are covered. Dr. Mack introduces the function of the gallbladder as a storage bag for bile, which is a 'detergent' produced

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by the liver that is used for digestion. Dr. Mack shows an illustration of the anatomy of the gastrointestinal tract, including the gallbladder, and describes where gallstones tend to form. Dr. Mack then shows actual gallstones, one a cholesterol stone, one a black pigment stone, and describes how gallstones form and the speed of growth of different types of stones. Risk factors for gallstones include being gender, being over 40, having a fair complexion (genetics), having a familial tendency, losing weight rapidly, and giving birth to many children. Symptoms include sudden onset of pain in the upper right quadrant of the abdomen, sometimes accompanied by nausea or vomiting. The pain is usually one to two hours in duration, as the gallstone passes. Some people have gallstones that are asymptomatic. Diagnostic considerations include patient history, abdominal film (xray), ultrasound, and cardiovascular testing (to rule out cardiovascular disease). Dr. Mack reviews the complications of gallstones, including gallstone pancreatitis, acute cholecystitis (infection of the gallbladder), hydrops, and jaundice. The program concludes by describing the use of open cholecystectomy, using a mini incision technique, and the use of laparoscopic cholecystectomy; Dr. Mack demonstrates the instruments used for the latter technique. The program concludes by referring viewers to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Bibliography: Multimedia on Gallstones The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in gallstones (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on gallstones: •

Bile and gallstones [slide] Source: McMaster University, Health Sciences; Year: 1978; Format: Slide; [Hamilton, Ont.]: The University, c1978

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Bile salts and gallstones [slide] Source: American Gastroenterological Association; Year: 1974; Format: Slide; [Thorofare, N. J.]: The Association; [Baltimore, Md.: for loan and sale by Milner-Fenwick], c1974

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Can gallstones be dissolved [videorecording] Source: Emory University School of Medicine; Year: 1975; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library], 1975

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Cholesterol gallstone formation [slide] Source: American Gastroenterological Association; Year: 1974; Format: Slide; [Thorofare, N. J.]: The Association, 1974

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Clinical aspects of cholelithiasis [slide] Source: American Gastroenterological Association; Year: 1974; Format: Slide; [Thorofare, N. J.]: The Association, 1974

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Extracorporeal shockwave lithotripsy for gallstones [videorecording] Source: author, Bruce D. Schirmer; co-author, R. Scott Jones; produced by DG, Davis & Geck, Medical Device Division; Year: 1990; Format: Videorecording; [Wayne, N.J.]: American Cyanamid Co., c1990

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Gallstones [slide]: surgery or drugs Source: presented by the Ohio Medical Education Network; Year: 1987; Format: Slide; [Columbus, Ohio]: The Network, [1987]

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Gallstones [videorecording] Source: Time Life Medical; produced in association with Sonalysts Studios; Year: 1996; Format: Videorecording; New York, NY: Patient Education Media, c1996

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Plain film radiographic diagnosis of gallstones and their complications [slide] Source: Robert N. Berk; Year: 1978; Format: Slide; Westport, Conn.: Medical Education Programs, c1978

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Problems related to diagnosis of gallstones [slide] Source: American Institute of Ultrasound in Medicine; Year: 1980; Format: Slide; [Bethesda, Md.]: The Institute, [1980]

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The Gallbladder: a study of structure and function; The formation of gallstones [filmstrip] Source: Trainex Corporation; Year: 1977; Format: Filmstrip; Garden Grove, Calif.: Trainex, c1977

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The Gallbladder, a study of structure and function [videorecording]: the formation of gallstones Source: Trainex Corporation; Year: 1977; Format: Videorecording; Garden Grove, Calif.: Trainex, c1977

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The Nonsurgical treatment of gallstones [videorecording] Source: with Susan Gordon and Ian Grimm; Year: 1989; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1989

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Treatment of gallstones [videorecording] Source: produced in the facilities of Instructional Media Services Television; Year: 1988; Format: Videorecording; [Seattle, Wash.]: University of Washington, c1988

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

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

German pensioner claims gallstone world record Source: Reuters Health eLine Date: July 07, 2003

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Exercise linked to lowered risk of gallstones Source: Reuters Health eLine Date: May 19, 2003

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Coffee reduces symptomatic gallstone disease in women Source: Reuters Medical News Date: December 05, 2002

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Coffee may lower women's gallstone risk Source: Reuters Health eLine Date: December 04, 2002

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Got gallstones? It may be in your genes: report Source: Reuters Health eLine Date: June 26, 2002

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Postmenopausal HRT a risk factor for gallstones Source: Reuters Industry Breifing Date: May 23, 2002

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Hormone replacement linked to gallstone risk Source: Reuters Health eLine Date: May 23, 2002

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Consensus panel endorses ERCP for symptomatic gallstone patients Source: Reuters Medical News Date: January 16, 2002

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Cisapride may prevent gallstones in patients taking octreotide Source: Reuters Industry Breifing Date: December 18, 2001

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Crohn's disease, multiple bowel resections increase risk of gallstones Source: Reuters Medical News Date: October 08, 2001

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Playing sports lowers risk of gallstones in obese Source: Reuters Health eLine Date: July 18, 2001

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ACAT2-deficient mice resist diet-induced hypercholesterolemia and gallstones Source: Reuters Medical News Date: December 01, 2000

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Serum glucose level predicts severe complications of gallstone pancreatitis Source: Reuters Medical News Date: September 20, 2000

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FDA approves Medstone's lithotripter for gallstones Source: Reuters Industry Breifing Date: September 08, 2000

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Specific motor defects identified in patients with gallstone recurrence Source: Reuters Medical News Date: August 10, 2000

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Vitamin C may help women steer clear of gallstones Source: Reuters Health eLine Date: April 10, 2000

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Researchers trace microscopic development of gallstones Source: Reuters Health eLine Date: January 26, 2000

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History of gallstones, smoking linked to gall bladder carcinoma Source: Reuters Medical News Date: September 23, 1999

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Regular exercise may prevent gallstone surgery Source: Reuters Health eLine Date: September 08, 1999

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Coffee consumption linked to reduced risk of gallstone disease Source: Reuters Medical News Date: June 09, 1999

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Drinking coffee may cut men's gallstone risk Source: Reuters Health eLine Date: June 08, 1999

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'Yo-yo' dieting raises gallstone risk Source: Reuters Health eLine Date: March 16, 1999

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Diet and physical activity factors in gallstone risk Source: Reuters Medical News Date: February 16, 1999

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Diet, exercise tied to gallstone risk Source: Reuters Health eLine Date: January 19, 1999

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Cirrhosis markedly increases risk of gallstones Source: Reuters Medical News Date: January 14, 1999

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NSAIDs not protective against gallstone formation Source: Reuters Medical News Date: September 21, 1998

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Vitamin C may lower gallstone risk Source: Reuters Health eLine Date: August 07, 1998

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Sonographic study of gallstone prevalence reveals predisposing factors Source: Reuters Medical News Date: July 03, 1998

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Gallstone Rx From Medstone Recommended For Approval Source: Reuters Medical News Date: May 04, 1998

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Regular Exercise Reduces Symptomatic Gallstone Disease In Men Source: Reuters Medical News Date: March 16, 1998

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Regular Exercise Prevents Gallstones Source: Reuters Health eLine Date: March 16, 1998

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Vitamin C And Alcohol Fight Gallstones Source: Reuters Health eLine Date: March 03, 1998

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Small Gallstones Linked To Pancreatitis, Watchful Waiting 'Unwarranted' Source: Reuters Medical News Date: August 11, 1997

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Endoscopic Balloon Dilation A "Viable" Option For Treatment Of Gallstones Source: Reuters Medical News Date: April 21, 1997

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Isoform Of Apolipoprotein E: Risk Factor For Gallstones Source: Reuters Medical News Date: December 09, 1996

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Reduced Gallbladder Emptying May Lead To More Gallstones Source: Reuters Medical News Date: September 13, 1996

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Aspirin Increases Gallbladder Motility In Patients With Cholelithiasis Source: Reuters Medical News Date: September 20, 1995

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Gallstone Formation Caused By Weight Reduction Preventable Source: Reuters Medical News Date: June 15, 1995

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Gallstone Formation Can Be Avoided In Obese Patients On Weight Loss Programs Source: Reuters Medical News Date: February 21, 1995 The NIH

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

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

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

Gallstones: A Common, Sometimes Serious Condition Source: Mayo Clinic Health Letter. 17(3): 7. March 1999. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: Most of the time, gallstones cause no symptoms and require no treatment. However, gallstones can sometimes be serious, even fatal, if left untreated. This brief report from the Mayo Clinic health newsletter offers information about gallstones. Most gallstones form when the patient's bile becomes chemically imbalanced and some of the cholesterol in the bile forms crystals. About 80 percent of gallstones produce no symptoms and require no treatment. Symptoms of gallstones can include episodes of intense, building pain in the upper abdomen; continuous (not intermittent) pain lasting 30 minutes to several hours; pain that may spread to the right shoulder blade or back; and nausea (sometimes with vomiting). Gallstones sometimes escape the gallbladder and enter nearby ducts. These migrating stones can cause serious complications and can be fatal if left untreated. The article outlines the risk factors for gallstones, including being female, being overweight, certain diet and dieting factors, age, and ethnicity. Gallstones that cause symptoms are usually treated by removing the gallbladder, a

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nonessential organ. Occasionally, conventional open abdominal surgery is the method of choice, but most often laparoscopic techniques are used. 1 figure. •

Gallstones: What to Do? Source: Digestive Health Matters. 4(1): 1-3. Spring 2002. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. Website: www.iffgd.org. Summary: This article helps readers who are diagnosed with gallstones determine their own best course of action. Although gallstones are present in 20 percent of women and 8 percent of men over the age of 40, most people are unaware of their presence and the consensus is that if they are not causing trouble, they should be left in place. Nevertheless, gallbladder removal (cholecystectomy) is one of the most common surgical procedures. The author reviews gallstones and their development, the prognosis of gallstones, how gallstones can cause symptoms, the symptoms they cause, other digestive tract symptoms that are not due to gallstones, complications of gallstones, diagnostic tests that may be used to confirm the presence or type of gallstones, and treatment options. 2 figures. 6 references.

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

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

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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to gallstones: Monoctanoin •

Local - U.S. Brands: Moctanin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202380.html

Ursodiol •

Systemic - U.S. Brands: Actigall http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202587.html

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

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

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 gallstones 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.”

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On this page (http://www.rarediseases.org/search/noddsearch.html), type “gallstones” (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 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 gallstones: •

Monooctanoin (trade name: Moctanin) http://www.rarediseases.org/nord/search/nodd_full?code=159

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 Institute12: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 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:14 •

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

13

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). 14 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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “gallstones” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “gallstones” (or synonyms) into the “For these words:” box. The following is a sample result: •

Gallstones (Cholelithiasis) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 180. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This fact sheet provides basic information on frequent signs and symptoms, causes, risk factors, preventive measures, etc.; treatment, medication, and diet; and when to contact one's health care provider. The fact sheet is designed to be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.

The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “gallstones” (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.

15 16

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

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).

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 25213 269 926 22 0 26430

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “gallstones” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 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.21 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.22 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/.

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

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

19

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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21 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. 22 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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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/.

The Genome Project and Gallstones In the following section, we will discuss databases and references which relate to the Genome Project and gallstones. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “gallstones” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for gallstones: •

Cholelithiasis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600803

•

Cholestasis with Gallstone, Ataxia, and Visual Disturbance Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?214980 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases:

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3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “gallstones” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. 24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

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The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “gallstones” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 gallstones can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to gallstones. 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 gallstones. 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 “gallstones”:

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Other guides Cirrhosis http://www.nlm.nih.gov/medlineplus/cirrhosis.html Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseases.html Gallbladder and Bile Duct Diseases http://www.nlm.nih.gov/medlineplus/gallbladderandbileductdiseases.html Kidney Stones http://www.nlm.nih.gov/medlineplus/kidneystones.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Pancreatic Cancer http://www.nlm.nih.gov/medlineplus/pancreaticcancer.html Pancreatic Diseases http://www.nlm.nih.gov/medlineplus/pancreaticdiseases.html

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

Diagnosis/Symptoms Abdominal Pain, Chronic: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/528.html ERCP (Endoscopic Retrograde Cholangiopancreatography) Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/ercp/index.htm How Is Gallbladder Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_gall_bladder_can cer_diagnosed_68.asp?sitearea=cri Ultrasound-Abdomen Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ultrasound-abdomen.htm Understanding EUS (Endoscopic Ultrasonography) Source: American Society for Gastrointestinal Endoscopy http://www.asge.org/gui/patient/eus.asp

•

Treatment About Cholecystectomy : Surgical Removal of the Gallbladder http://www.facs.org/public_info/operation/cholesys.pdf Cholecystectomy: Open and Laparoscopic http://www.nlm.nih.gov/medlineplus/tutorials/cholecystectomyloader.html

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Extrahepatic Bile Duct Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/bileduct/patient/ Gallbladder Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/gallbladder/patient/ Gallbladder Removal: Laparoscopic Method Source: American Academy of Family Physicians http://familydoctor.org/handouts/114.html •

Specific Conditions/Aspects Bile Reflux Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00259 Diarrhea: A Concern After Gallbladder Removal? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00067 JAMA Patient Page: Acute Cholecystitis Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ0MTIRMAD &sub_cat=193 Primary Biliary Cirrhosis Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/primarybiliarycirrhosis/index.ht m Primary Sclerosing Cholangitis Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/primarysclerosingcholangitis/ind ex.htm

•

Children Biliary Atresia Source: Children's Liver Association for Support Services http://www.classkids.org/library/biliaryatresia.htm

•

Organizations American Gastroenterological Association http://www.gastro.org/ American Liver Foundation http://www.liverfoundation.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/

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Prevention/Screening Can Gallbladder Cancer Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_can_gall_bladder_cancer _be_prevented_68.asp?sitearea=cri

•

Research Noninvasive Diagnosis of Biliary Disease Source: American College of Physicians http://www.annals.org/cgi/content/full/139/7/I-32

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 gallstones. 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: •

Gallstones: A National Health Problem Source: Cedar Grove, NJ: American Liver Foundation. 4 p. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 223-0179 or (201) 256-2550. PRICE: $0.50 each; $6 for 25 copies; $12 for 50 copies (as of 1995); discounts available for larger quantities. Summary: An estimated 20 million Americans, more than 10 percent of the population, have gallstones. Another million develop gallstones each year. Recognition and understanding of the problem is needed to support research to find solutions to the problem. Information is provided on the gallbladder and its function and on gallstones: their causes, symptoms, diagnosis, and treatment.

•

Gallstones Source: Bethesda, MD: American Gastroenterological Association. 199x. [4 p.]. Contact: American Gastroenterological Association (AGA). 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (800) 668-5237 or (301) 654-2055. Fax (301) 652-3890. Website: www.gastro.org. PRICE: Single copy free; bulk copies available. Summary: Gallstone disease is a common medical problem in the United States. This brochure from the American Gastroenterological Association (AGA) reviews the

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problem of gallstones and advances in the diagnosis and treatment of this condition. Topics include a definition of gallstones and how they form, diagnostic tests used to confirm the presence of gallstones, and treatment options. Gallstones form when the components of bile (a digestive juice) precipitate out of solution and form crystals. Pigment (bilirubin) gallstones and cholesterol gallstones are the most common types. The most typical symptom of gallstone disease is severe steady pain in the upper abdomen or right side. If the blockage caused by a gallstone is prolonged, the gallbladder may become inflamed (acute cholecystitis), which usually requires hospitalization for treatment. Abdominal ultrasound and oral cholecystograms are used to diagnose gallstones. Surgical removal of the gallbladder (cholecystectomy) remains the most widely used therapy for gallstones; surgical options include the standard open procedure and a less invasive procedure using laparoscopy ('belly button surgery'). Alternatives to surgery include endoscopic removal of the stone, chemical dissolution, and lithotripsy (in which sound waves are used to disintegrate the stones). Unfortunately, in all nonsurgical approaches, the gallstones tend to recur in about half of patients treated. The brochure includes a diagram of the digestive tract, with organs labeled. 2 figures. •

Gallstones and Laparoscopic Cholecystectomy Source: JAMA. Journal of the American Medical Association. 269(8): 1018-1024. February 1993. Contact: Also available in booklet form (Volume 10, Number 3, September 14-16 1992) from the Office of Medical Applications of Research, National Institutes of Health, Federal Building, Room 618, Bethesda, MD 20892. Summary: This article presents the NIH consensus statement on Gallstones and Laparoscopic Cholecystectomy, as developed at the NIH Consensus Development Conference held in September 1992. The specific problems and patient issues that must be evaluated in dealing with this disease were addressed by surgeons, endoscopists, hepatologists, gastroenterologists, radiologists, epidemiologists, and representatives of the general public. After 2 days of presentations by medical experts and discussion by the audience, the consensus panel addressed six topics: which patients with gallstones should be treated, which patients should be treated with laparoscopic cholecystectomy, the alternative medical and surgical treatments of gallstone disease, the comparative results of laparoscopic cholecystectomy with open cholecystectomy and other available treatments, how bile duct stones should be detected and treated, and future directions for research in the prevention and management of gallstone disease and in laparoscopic surgery. The article concludes with a listing of the names and affiliations of the panel members, the speakers, and the planning committee.

•

Gallstones and Laparoscopic Cholecystectomy: Summary of the NIH Consensus Source: Bethesda, MD: Office of Medical Applications of Research, National Institutes of Health. 1992. 2 p. Contact: Available from Office of Medical Applications of Research, National Institutes of Health. Federal Building, Room 618, Bethesda, MD 20892. (301) 496-1143. PRICE: Single copy free. Summary: This fact sheet summarizes the NIH consensus statement on Gallstones and Laparoscopic Cholecystectomy, as developed at the NIH Consensus Development Conference held in September 1992. After a brief review of the problem of gallstones in the United States and the history of their treatment, the consensus panel addressed six

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topics: which patients with gallstones should be treated, which patients should be treated with laparoscopic cholecystectomy, the alternative medical and surgical treatments for gallstone disease, the comparative results of laparoscopic cholecystectomy with open cholecystectomy and other available treatments, how bile duct stones should be detected and treated, and the future directions for research in the prevention and management of gallstone disease and in laparoscopic surgery. •

Gallstones: Finding Relief for an Uncomfortable Problem Source: San Bruno, CA: StayWell Company. 1999. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. E-mail: [email protected]. Website: www.staywell.com. PRICE: $17.95 for pack of 50; plus shipping and handling. Summary: This patient education brochure describes gallstones and their treatment. Written in nontechnical language, the brochure first lists the populations in which gallstones are more likely: women (especially those who have been pregnant), people of American Indian or Hispanic descent, people who are overweight, people who have lost weight quickly, women who have taken estrogen birth control pills or hormone replacement therapy, and people who eat a high fat diet. Common symptoms of gallstones range from no symptoms to disabling pain and can include mild to severe pain in the upper abdomen; frequent stomach upset, burping, or bloating; fever, nausea, or vomiting; or jaundice (a liver problem that makes the skin yellowish). Gallstones may be found on x rays done for other reasons, or symptoms may lead the physician to suspect gallstones. Diagnosis will include the patient's medical history and some diagnostic tests such as ultrasound, x rays, and endoscopic retrograde cholangiopancreatography (ERCP). Treatments for gallstones include monitoring (watchful waiting), medications to dissolve the stones, ERCP, or surgery (laparoscopic cholecystectomy or open cholecystectomy, both of which remove the gallbladder). One section of the brochure illustrates the gallbladder and surrounding organs and describes how gallstones form. The last page of the brochure summarizes the recommendations for preventing future gallstones, notably by eating a low fat diet. The brochure is illustrated with full color line drawings. 7 figures.

•

Gallstones and Their Treatment: A Guide for Patients Source: San Ramon, CA: HIN, Inc., The Health Information Network. 1995. 25 p. Contact: Available from HIN, Inc. 231 Market Place, Number 331, San Ramon, CA 94583. (800) HIN-1121. Fax (925) 358-4377. Website: www.hinbooks.com. PRICE: $36.25 plus shipping per set of 25 booklets; quantity discounts available. Order Number 0201. ISBN: 188527421x. Summary: This patient education brochure familiarizes readers with gallstones and their treatment. It is written in non-technical language and includes information about what gallstones are; how they develop; risk factors; complications; symptoms; diagnostic tests; treatment options; preparing for laparoscopic surgery; the operation itself; recovery after surgery; and nonsurgical treatment options. The brochure is illustrated with simple line drawings and figures and includes a glossary.

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Dieting and Gallstones Source: Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 4 p., 1993. Contact: Weight-Control Information Network, 1 WIN WAY, BETHESDA, MD 208923665. (301) 570-2178 OR (800) 946-8098. Summary: This patient education brochure provides an overview of the problems associated with low-calorie diets and the development of gallstones. The difference between silent and symptomatic gallstones is explained. Overweight people are at greater risk of developing gallstones than people of average weight. People who are considering embarking on a diet program requiring very low intake of calories each day should be aware that during rapid or substantial weight loss, a person's risk of developing gallstones is increased. The risks and benefits of weight loss are considered, along with a discussion of possible treatment for gallstones and a suggested reading list.

•

Gallstones at Time of Diagnosis Source: New York, NY: Patient Education Media, Inc. Time Life Medical. 1996. (videocassette). Contact: Available from Milner-Fenwick, Inc. 2125 Greenspring Drive, Timonium, MD 21093. (800) 432-8433. Fax (410) 252-6316. Website: www.milner-fenwick.com. Summary: This videocassette program provides information for patients newly diagnosed with gallstones. The half-hour, newsmagazine style educational program features four sections or 'reports.' The first report examines what is going on inside the body and how the diagnosis was made; computer animation is used to aid viewer understanding. The second report discusses what happens after the diagnosis and introduces the viewer to practical issues, including the types of health professionals they may encounter and what lifestyle changes may need to occur. The third report explores options for treatment and management of the condition. The final report addresses issues and answers common questions through the use of an in-studio question and answer session. The videotape comes with a personal workbook that includes the program highlights, a glossary, a resource guide, and blank space for readers to record their personal medical journal. (AA-M).

•

Your Gallstones: Diagnosis and Treatment Source: Washington, DC: Digestive Disease National Coalition. 1991. 4 p. Contact: Available from Digestive Disease National Coalition. 711 Second Street, NE, Suite 2. Washington, DC 20002. (202) 544-7497. PRICE: Single copy free. Summary: Written in a question and answer format, this brochure reviews the diagnosis and treatment of common gallstones. Topics include the role of the gallbladder, the occurrence of gallstones, how rapid weight loss affects the formation of gallstones, the symptoms of gallstones, how gallstones are diagnosed, how gallstones typically progress, traditional surgical treatment of gallstones, laparoscopic removal of the gallbladder, oral medication used for dissolving cholesterol gallstones, and shock wave lithotripsy used to fragment the stones. The brochure stresses the importance of learning about all the options available to treat gallstones, in order to make an informed decision about treatment. 4 figures.

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

Treatment of gallstone and gallbladder disease Source: Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society; 1996 (revised 2000); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1704&nbr=930&am p;string=gallstones Healthfinder™

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

Dieting and Gallstones Summary: This online document gives consumers basic information on gallstones and the effect of weight loss on this condition. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1448

•

Gallstones Summary: Gallstones are pieces of solid material that form in the gallbladder. This consumer health information fact sheet contains basic information about this digestive disorder. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2745

•

Gallstones: A National Health Problem Summary: This online document was written for consumers and answers questions about the causes, diagnosis, prognosis and treatment of this disorder. Source: American Liver Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2211 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

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ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to gallstones. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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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 “gallstones” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “gallstones”. 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 “gallstones” (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 “gallstones” (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.26

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

26

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)27: •

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/

27

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 gallstones: •

Basic Guidelines for Gallstones Cholelithiasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000273.htm

•

Signs & Symptoms for Gallstones Abdominal fullness, gaseous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003124.htm Abdominal indigestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003260.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm

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Gas/flatus, excessive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003124.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Gallstones Abdominal CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003789.htm Abdominal MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003796.htm Abdominal ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003777.htm Abdominal X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003815.htm Bilirubin; urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003595.htm Endoscopic retrograde cholangiopancreatography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003893.htm ERCP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003893.htm Fecal fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003588.htm Gall bladder radionuclide scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003826.htm Oral cholecystogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003821.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

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Nutrition for Gallstones Cholesterol Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002472.htm

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Fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm •

Surgery and Procedures for Gallstones Cholecystectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002930.htm

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Background Topics for Gallstones Bile Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002237.htm Biliary system Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002240.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Symptomatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002293.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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GALLSTONES DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Kinase: An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated

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

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] 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] Amenorrhea: Absence of menstruation. [NIH]

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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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU]

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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-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] 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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU]

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Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [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] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atelectasis: Incomplete expansion of the lung. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Bacteraemia: The presence of bacteria in the blood. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the

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coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basilar Artery: The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. [NIH] Belching: Noisy release of gas from the stomach through the mouth. Also called burping. [NIH]

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

Bezoar: A ball of food, mucus, vegetable fiber, hair, or other material that cannot be digested in the stomach. Bezoars can cause blockage, ulcers, and bleeding. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Fistula: Abnormal passage in any organ of the biliary tract or between biliary organs and other organs. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH]

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Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bladder Calculi: Calculi of the urinary bladder; also known as vesical calculi or bladder stones, and cystoliths. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH]

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Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Butterflies: Slender-bodies diurnal insects having large, broad wings often strikingly colored and patterned. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU]

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

Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject

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or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [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 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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the

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relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [NIH] Cholangiography: Radiographic examination of the bile ducts. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholecystography: Radiography of the gallbladder after ingestion of a contrast medium. [NIH]

Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholecystostomy: Establishment of an opening into the gallbladder either for drainage or surgical communication with another part of the digestive tract, usually the duodenum or jejunum. [NIH] Choledocholithiasis: Gallstones in the bile ducts. [NIH] Cholelithiasis: Presence or formation of gallstones. [NIH] Choleretic: A choleretic agent. [EU] Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH]

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Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] 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 Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the 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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [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 photocoagulation. [EU] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but

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some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [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

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addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH]

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Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Convalescence: The period of recovery following an illness. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cryoelectron Microscopy: Electron microscopy involving rapid freezing of the samples. The imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the

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transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [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] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydrocholic Acid: A semisynthetic bile acid made from cholic acid. It is used as a cholagogue, hydrocholeretic, diuretic, and as a diagnostic aid. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH]

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Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent. [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] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] 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 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] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH]

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Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilate: Relax; expand. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissection: Cutting up of an organism for study. [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] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diurnal: Occurring during the day. [EU] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU]

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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Edetic Acid: A chelating agent (chelating agents) that sequesters a variety of polyvalent cations. It is used in pharmaceutical manufacturing and as a food additive. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsify: To convert or to be converted into an emulsion. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopic retrograde cholangiopancreatography: ERCP. A procedure to x-ray the pancreatic duct, hepatic duct, common bile duct, duodenal papilla, and gallbladder. In this

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procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemics: A period of increased prevalence of a particular disease in a population. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] ERCP: Endoscopic retrograde cholangiopancreatography (en-do-SKAH-pik RET-ro-grade ko-LAN-jee-o-PAN-kree-a-TAW-gra-fee). A procedure to x-ray the bile and pancreatic ducts. In this procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH]

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Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [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] Evacuation: An emptying, as of the bowels. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH]

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Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] Flatus: Gas passed through the rectum. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallbladder Emptying: A process whereby bile is delivered from the gallbladder into the duodenum. The emptying is caused by both contraction of the gallbladder and relaxation of the sphincter mechanism at the choledochal terminus. [NIH] Gallic Acid: A colorless or slightly yellow crystalline compound obtained from nutgalls. It is used in photography, pharmaceuticals, and as an analytical reagent. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH]

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Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [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]

Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in

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the study of genetics. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] 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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into

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three groups: neutrophils, eosinophils, and basophils. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the

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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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemoptysis: Bronchial hemorrhage manifested with spitting of blood. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatic Duct, Common: Predominantly extrahepatic bile duct which is formed by the junction of the right and left hepatic ducts, which are predominantly intrahepatic, and, in turn, joins the cystic duct to form the common bile duct. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hepatoma: A liver tumor. [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] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird

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and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU]

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Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]

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

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signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inguinal Hernia: A small part of the large or small intestine or bladder that pushes into the groin. May cause pain and feelings of pressure or burning in the groin. Often requires surgery. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] 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] Instillation: . [EU] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] 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] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin

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or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isopropyl: A gene mutation inducer. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]

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Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lenticular: 1. Pertaining to or shaped like a lens. 2. Pertaining to the crystalline lens. 3. Pertaining to the lenticular nucleus. [EU] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Leukemia: Cancer of blood-forming tissue. [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] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and

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is itself absorbed. It is used as cholagogue and choleretic. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Lithotripsy, Laser: Fragmentation of calculi, notably urinary or biliary, by laser. It is usually performed with an endoscopically guided pulsed tunable dye laser, a combination of a pulsed laser and a dye laser usually referred to as a pulsed dye laser. It is both safe and effective when extracorporeal shockwave lithotripsy is infeasible or unsuccessful. [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 Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-calorie diet: Caloric restriction of about 800 to 1,500 calories (approximately 12 to 15 kcal/kg of body weight) per day. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [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] 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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] 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

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radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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 Microdomains: Detergent-insoluble cell membrane components. They are enriched in sphingolipids and cholesterol and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins. [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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menopause: Permanent cessation of menstruation. [NIH]

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Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [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] Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Micelles: Electrically charged colloidal particles or ions consisting of oriented molecules; aggregates of a number of molecules held loosely together by secondary bonds. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes

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place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

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] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucoproteins: Conjugated proteins in which mucopolysaccharides are combined with proteins. The mucopolysaccharide moiety is the predominant group with the protein making up only a small percentage of the total weight. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiparous: 1. Having had two or more pregnancies which resulted in viable fetuses. 2. Producing several ova or offspring at one time. [EU] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH]

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Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH]

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Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Office Management: Planning, organizing, and administering activities in an office. [NIH]

196 Gallstones

Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Oral Dissolution Therapy: A method of dissolving cholesterol gallstones. The patient takes the oral medications chenodiol (KEE-noh-DY-awl) (Chenix) and ursodiol (ERS-oh-DY-awl) (Actigall). These medicines are most often used for people who cannot have an operation. [NIH]

Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [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] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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 Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH]

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Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilla: A small nipple-shaped elevation. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH]

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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] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Percutaneous transhepatic cholangiography: A procedure to x-ray the hepatic and common bile ducts. A contrasting agent is injected into the liver or bile duct, and the ducts are then xrayed to find the point of obstruction. Also called PTC. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [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

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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] Phenotypes: An organism as observed, i. e. as judged by its visually perceptible characters resulting from the interaction of its genotype with the environment. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild

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rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plant sterols: Plant-based compounds that can compete with dietary cholesterol to be absorbed by the intestines. This results in lower blood cholesterol levels. They may have some effect in cancer prevention. Also known as phytosterols. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [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] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH]

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Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Postcholecystectomy Syndrome: A condition that occurs after gallbladder removal. The muscle between the gallbladder and the small intestine does not work properly, causing pain, nausea, and indigestion. Also called biliary dyskinesia. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] 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] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH]

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Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] 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 C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora,

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Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [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]

Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. [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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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.

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Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [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] Radiolucent: Partly or wholly permeable to X-rays or other forms of radiation contrasted with radiopaque. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in

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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] Recuperation: The recovery of health and strength. [EU] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [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] 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU]

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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] Rod: A reception for vision, located in the retina. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol

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triphosphate system, and the cyclic GMP system. [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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] 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

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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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [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] Sludge: A clump of agglutinated red blood cells. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [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] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] 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] Spasmolytic: Checking spasms; antispasmodic. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In

Dictionary 209

taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spherocytes: Small, abnormal spherical red blood cells with more than the normal amount of hemoglobin. [NIH] Spherocytosis: A condition in which there are abnormally thick, almost spherical, red blood cells or spherocytes in the blood. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [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]

Stagnation: The slowing down or stoppage of the flowing of any fluid. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

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

210 Gallstones

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stump: The end of the limb after amputation. [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] Subhepatic: The lower part of the supracolic division of the peritoneal cavity. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Symbiosis: The living together of organisms of different species. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU]

Dictionary 211

Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of

212 Gallstones

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] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] Tonicity: The normal state of muscular tension. [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] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trifluoroacetic Acid: A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis. [NIH]

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Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] 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] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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

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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] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [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] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [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] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until

Dictionary 215

symptoms appear or change. Also called observation. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Zygote: The fertilized ovum. [NIH]

217

INDEX A Abdominal Pain, 52, 82, 94, 140, 159, 181, 188, 198 Ablate, 159, 177 Ablation, 87, 159 Abscess, 32, 38, 45, 46, 47, 50, 159 Acceptor, 159, 196 Acetylcholine, 159, 170, 195 Acetylcysteine, 78, 159 Acoustic, 10, 91, 159, 163 Adaptability, 159, 168 Adenocarcinoma, 159, 184 Adenosine, 159, 166, 199 Adenylate Kinase, 99, 159 Adhesions, 46, 94, 159 Adipocytes, 159, 189 Adjustment, 6, 15, 159 Adrenal Cortex, 159, 179, 201 Adsorption, 18, 159 Adsorptive, 159, 160 Adverse Effect, 160, 207 Aerobic, 160, 192 Afferent, 160, 189 Affinity, 160, 208 Agar, 160, 200 Agonist, 24, 160, 204 Alertness, 160, 166 Algorithms, 160, 165 Alimentary, 18, 41, 45, 46, 47, 49, 50, 62, 67, 146, 160, 197, 198 Alkaline, 13, 160, 161, 166 Alkaline Phosphatase, 13, 160 Alleles, 160, 184 Allergen, 160, 175 Alternative medicine, 36, 65, 120, 160 Amenorrhea, 160, 200 Amino Acid Sequence, 161, 162, 181 Amino Acids, 161, 170, 178, 181, 198, 200, 202, 206, 212, 213 Ammonia, 110, 161 Ampulla, 161, 169, 177 Amputation, 161, 210 Anaesthesia, 161, 186 Anal, 15, 20, 161 Analog, 161, 195 Analogous, 161, 176, 212 Anatomical, 161, 165, 186, 206 Anemia, 97, 135, 161, 166, 203, 211

Anesthesia, 81, 161 Angina, 86, 97, 161 Angina Pectoris, 86, 97, 161 Animal model, 161, 213 Anionic, 63, 161 Anions, 19, 161, 188, 207 Anode, 161 Anovulation, 161, 200 Antagonism, 161, 166 Antibacterial, 161, 209 Antibiotic, 13, 161, 162, 166, 178, 209 Antibodies, 162, 183, 184, 186 Antibody, 160, 162, 171, 183, 185, 186, 188, 191, 193, 203, 204, 209, 215 Antigen, 160, 162, 171, 185, 186, 191, 204 Anti-infective, 162, 185, 188 Anti-inflammatory, 85, 162, 163 Anti-Inflammatory Agents, 162, 163 Antispasmodic, 162, 208 Antiviral, 159, 162 Anus, 161, 162, 165 Aorta, 162 Aortic Aneurysm, 33, 162 Aperture, 79, 162 Apolipoproteins, 162, 189 Aponeurosis, 162, 180 Apoptosis, 18, 162, 167 Aqueous, 12, 19, 78, 92, 162, 164, 174, 177, 185, 189 Arachidonic Acid, 162, 202 Arginine, 162, 195 Arterial, 162, 163, 169, 185, 202, 211 Arteries, 162, 163, 164, 165, 173, 190, 192, 194 Arterioles, 163, 165, 167, 192, 194 Arteriolosclerosis, 163 Arteriosclerosis, 85, 96, 163, 185, 194 Aspiration, 11, 80, 90, 163 Aspirin, 85, 120, 163 Assay, 23, 163, 204 Asymptomatic, 7, 8, 11, 14, 15, 33, 44, 45, 46, 86, 97, 108, 109, 114, 163, 197 Ataxia, 134, 135, 163, 211 Atelectasis, 11, 163 Atrophy, 81, 135, 163, 194 Attenuation, 14, 163 Auditory, 163, 191 Auditory nerve, 163, 191

218 Gallstones

Autodigestion, 163, 197 Autoimmune disease, 83, 163 B Bacteraemia, 47, 163 Bacteria, 46, 48, 159, 161, 162, 163, 164, 172, 175, 178, 179, 181, 184, 192, 204, 209, 212, 214 Bactericidal, 163, 179 Bacteriophage, 163, 200, 212 Bacteriostatic, 164, 178 Bacterium, 164, 172, 184 Basal Ganglia, 163, 164, 180 Basal Ganglia Diseases, 163, 164 Base, 58, 164, 175, 181, 188, 211, 213 Base Sequence, 164, 181 Basilar Artery, 164, 191 Belching, 104, 164 Benign, 8, 163, 164, 180, 183, 194, 204 Bezoar, 70, 164 Bilateral, 164, 200 Bile, 3, 4, 5, 7, 10, 11, 12, 13, 14, 16, 17, 18, 19, 22, 23, 24, 25, 26, 27, 28, 29, 34, 37, 41, 42, 45, 52, 53, 54, 56, 57, 62, 63, 64, 65, 78, 81, 82, 83, 84, 85, 86, 88, 89, 90, 92, 94, 95, 96, 99, 104, 107, 108, 109, 110, 113, 114, 121, 140, 141, 143, 144, 157, 164, 165, 169, 170, 173, 174, 175, 177, 178, 180, 181, 184, 188, 189, 190, 198, 209, 211, 214 Bile Acids, 14, 16, 19, 24, 26, 27, 29, 82, 83, 89, 96, 104, 164, 181, 209, 211 Bile Acids and Salts, 164 Bile Ducts, 13, 84, 92, 109, 164, 169, 180 Bile Pigments, 164, 188 Biliary Fistula, 110, 164 Biliary Tract, 8, 12, 52, 53, 82, 83, 87, 88, 92, 107, 110, 164, 166, 197 Bilirubin, 12, 13, 18, 37, 54, 67, 78, 88, 143, 156, 164, 165, 180, 185 Biochemical, 28, 160, 165, 181 Biological Transport, 165, 175 Biopsy, 165, 198 Biosynthesis, 23, 29, 86, 96, 162, 165, 190, 208 Biotechnology, 30, 31, 106, 120, 131, 134, 135, 136, 165 Bladder Calculi, 43, 165 Bloating, 144, 165, 186, 188, 195 Blood Coagulation, 165, 166 Blood pressure, 165, 167, 185, 193, 208 Blood vessel, 86, 97, 165, 167, 168, 178, 184, 188, 190, 208, 210, 211, 214

Body Fluids, 165, 166, 176, 208 Body Mass Index, 14, 15, 165, 196 Body Regions, 165, 171 Bone Marrow, 165, 173, 190 Bone scan, 165, 206 Bowel, 29, 69, 109, 118, 161, 165, 176, 187, 189, 195, 198, 210 Bowel Movement, 165, 176, 210 Brachytherapy, 165, 187, 188, 203, 215 Bradykinin, 166, 195 Branch, 153, 166, 191, 197, 203, 208, 211 Breakdown, 166, 176, 180, 208 Broad-spectrum, 13, 166 Bromine, 88, 166 Butterflies, 104, 166 Bypass, 26, 166 C Cadmium, 26, 166 Cadmium Poisoning, 166 Caffeine, 4, 53, 166 Calcification, 56, 163, 166 Calcium, 12, 17, 18, 25, 27, 29, 55, 56, 63, 64, 66, 67, 78, 80, 94, 166, 171, 192, 207 Calcium Carbonate, 64, 66, 67, 80, 166 Calculi, 44, 79, 82, 88, 92, 165, 166, 182, 190 Cannula, 81, 166 Capillary, 166, 167, 214 Capillary Fragility, 167 Carbohydrate, 110, 167, 182, 200 Carbon Dioxide, 10, 167, 199, 205 Carcinogenic, 167, 187, 209 Carcinogens, 167, 170, 196 Carcinoma, 35, 38, 39, 45, 46, 58, 119, 167 Cardiac, 166, 167, 181, 183, 194, 209 Cardiopulmonary, 10, 167 Cardiovascular, 22, 56, 114, 167 Cardiovascular disease, 22, 114, 167 Carnitine, 99, 167 Carrier Proteins, 167, 204 Case report, 17, 41, 167 Case series, 11, 167 Caspase, 26, 167 Cataracts, 97, 98, 100, 167 Catechin, 99, 167 Catheters, 90, 167, 186, 187 Cations, 168, 177, 188 Causal, 86, 96, 168, 184 Cause of Death, 27, 168 Caveolae, 23, 168 Caveolins, 168 Cell Death, 26, 162, 168, 194 Cell Differentiation, 168, 207

Index 219

Cell Division, 135, 163, 168, 193, 200 Cell membrane, 27, 100, 165, 167, 168, 175, 188, 191, 199 Cell Membrane Structures, 168 Cell proliferation, 163, 168, 207 Cell Respiration, 168, 192, 205 Cellobiose, 168 Cellulose, 65, 168, 200 Central Nervous System, 159, 166, 168, 169, 180, 183 Cerebellar, 163, 168, 205 Cerebral, 101, 163, 164, 168, 208 Cerebrovascular, 164, 167, 168, 211 Cerebrum, 168, 213 Character, 161, 168, 174 Chelating Agents, 169, 177 Chemotherapy, 26, 169 Chenodeoxycholic Acid, 50, 66, 78, 86, 89, 104, 169, 214 Chest Pain, 103, 169 Chlorine, 88, 169 Chloroform, 92, 169 Cholangiography, 7, 13, 45, 169 Cholangitis, 5, 7, 10, 12, 81, 90, 107, 108, 110, 141, 169 Cholecystitis, 7, 8, 10, 13, 14, 24, 34, 43, 81, 87, 94, 107, 108, 109, 110, 114, 141, 143, 169 Cholecystography, 7, 169 Cholecystokinin, 43, 53, 85, 94, 169 Cholecystostomy, 87, 92, 109, 169 Choledocholithiasis, 107, 108, 110, 169 Choleretic, 169, 175, 190, 214 Cholestanol, 55, 64, 169 Cholestasis, 18, 83, 104, 105, 134, 169 Cholesterol Esters, 169, 189 Cholic Acid, 19, 89, 170, 174 Choline, 19, 60, 170, 199 Cholinergic, 25, 170 Chromatin, 162, 170 Chromium, 37, 54, 170 Chromosome, 170, 172, 183, 184, 189 Chronic Disease, 81, 170 Chronic renal, 43, 170, 200, 213 Chylomicrons, 170, 189 CIS, 24, 170 Clamp, 25, 84, 170 Clear cell carcinoma, 170, 175 Clinical Medicine, 49, 170, 201 Clinical trial, 18, 75, 76, 85, 131, 170, 173, 197, 204 Cloning, 165, 170

Coagulation, 165, 170, 184, 211 Codon, 170, 181 Coenzyme, 171, 190, 208 Cofactor, 171, 202 Colic, 7, 11, 16, 44, 82, 89, 107, 108, 171 Colitis, 70, 109, 171, 187, 188 Collagen, 167, 171, 181, 200 Collapse, 81, 166, 171 Colloidal, 171, 192, 207 Colorectal, 110, 171 Combinatorial, 97, 171 Common Bile Duct, 10, 15, 24, 36, 46, 87, 89, 95, 108, 110, 171, 173, 184, 198 Complement, 171, 172 Complementary and alternative medicine, 61, 74, 171 Complementary medicine, 61, 172 Computational Biology, 131, 134, 172 Computed tomography, 7, 12, 14, 16, 56, 172, 206 Computerized axial tomography, 172, 206 Computerized tomography, 172 Concretion, 166, 172 Conjugated, 18, 164, 169, 170, 172, 174, 175, 189, 193 Conjugation, 96, 172 Connective Tissue, 165, 171, 172, 179, 180, 181 Consciousness, 172, 174 Constipation, 172, 188, 198 Constriction, 173, 188 Consumption, 4, 32, 36, 52, 54, 63, 65, 119, 173, 175, 181, 205 Contractility, 5, 25, 55, 58, 173, 177 Contraindications, ii, 173 Control group, 14, 20, 173 Convalescence, 87, 173 Coordination, 30, 169, 173 Coronary, 27, 58, 86, 96, 100, 161, 167, 173, 192, 194 Coronary Circulation, 161, 173 Coronary heart disease, 58, 86, 97, 100, 167, 173 Coronary Thrombosis, 173, 192, 194 Corpus, 173, 197, 201 Corpus Luteum, 173, 201 Cortex, 163, 173, 205 Cortical, 173, 179, 207, 211 Cryoelectron Microscopy, 18, 173 Crystallization, 27, 28, 56, 96, 97, 173 Curative, 173, 195, 211 Cyclic, 29, 166, 173, 183, 195, 202, 206

220 Gallstones

Cyclosporine, 33, 173 Cyst, 165, 173 Cysteine, 159, 173 Cystic Duct, 81, 89, 94, 171, 173, 184 Cytochrome, 26, 173 Cytoplasm, 100, 162, 168, 174, 182, 206 Cytoprotection, 24, 174 Cytoskeleton, 174, 192 Cytotoxic, 26, 174, 204, 207 D Dairy Products, 174, 206 Databases, Bibliographic, 131, 174 Decompression, 90, 174 Decompression Sickness, 174 Degenerative, 174, 184 Dehydrocholic Acid, 89, 174 Deletion, 162, 174 Dementia, 100, 174 Dendrites, 175, 194 Density, 23, 86, 97, 165, 175, 189, 196, 208 Dental Caries, 175, 180 Deoxycholic Acid, 26, 33, 89, 175 Depolarization, 175, 207 DES, 54, 175 Desensitization, 24, 175 Detoxification, 110, 175 Deuterium, 175, 185 Developed Countries, 107, 175 Diabetes Mellitus, 14, 22, 32, 86, 97, 110, 175, 182, 184, 195 Diagnostic Imaging, 34, 175 Diagnostic procedure, 7, 77, 121, 175 Dialyzer, 175, 183 Diaphragm, 175, 184 Diarrhea, 104, 141, 175, 188 Diastolic, 175, 185 Diffusion, 24, 165, 175, 188, 213 Digestion, 32, 83, 84, 103, 114, 160, 164, 165, 176, 186, 187, 190, 198, 209 Digestive system, 76, 104, 176, 181 Digestive tract, 104, 122, 143, 169, 176, 208 Dihydrotestosterone, 176, 205 Dilate, 89, 176 Dimerization, 28, 176 Diploid, 176, 200 Direct, iii, 7, 13, 24, 25, 27, 28, 96, 110, 123, 170, 176, 205, 210 Disinfectant, 176, 179 Dissection, 93, 176 Distal, 31, 84, 89, 90, 91, 176, 181, 203 Diuresis, 166, 176 Diuretic, 174, 176

Diurnal, 166, 176 Domesticated, 176, 183 Dorsum, 176, 180 Drive, ii, vi, 3, 9, 12, 17, 51, 91, 101, 107, 108, 132, 145, 176, 188 Drug Design, 21, 124, 125, 176 Drug Interactions, 104, 124, 176 Duodenum, 17, 81, 83, 84, 89, 90, 95, 164, 169, 176, 177, 178, 180, 188, 196, 197, 209 Dyskinesia, 94, 176, 201 Dyspepsia, 11, 86, 176, 186 Dysplasia, 135, 176 Dystrophy, 135, 176 E Edema, 101, 177, 213 Edetic Acid, 64, 177 Effector, 159, 171, 177, 195 Effector cell, 177, 195 Efficacy, 13, 26, 176, 177, 212 Ejection fraction, 48, 94, 177 Elasticity, 163, 177 Elective, 107, 108, 177 Electrocoagulation, 81, 170, 177 Electrolysis, 161, 168, 177 Electrolyte, 28, 177, 183, 201, 208, 213 Electrons, 164, 177, 188, 196, 203, 204 Embryo, 168, 177, 186 Empyema, 110, 177 Emulsify, 89, 177 Emulsion, 177 Endocytosis, 168, 177 Endoscope, 177, 178 Endoscopic, 5, 6, 7, 13, 15, 16, 17, 36, 37, 38, 90, 94, 120, 140, 143, 144, 156, 177, 178 Endoscopic retrograde cholangiopancreatography, 6, 7, 8, 15, 16, 90, 144, 156, 177, 178 Endothelium, 178, 195 Endothelium-derived, 178, 195 End-stage renal, 170, 178, 200 Energy balance, 178, 189 Enterohepatic, 37, 54, 110, 178 Enterohepatic Circulation, 110, 178 Environmental Exposure, 178, 196 Environmental Health, 130, 132, 178 Enzymatic, 28, 166, 171, 175, 178 Epidemics, 49, 178 Epidemiological, 13, 14, 22, 37, 54, 55, 178 Epigastric, 178, 196 ERCP, 6, 7, 15, 90, 118, 140, 144, 156, 177, 178

Index 221

Erectile, 178, 197 Erythrocytes, 19, 161, 165, 178, 184, 205 Erythromycin, 49, 53, 178 Esophageal, 178, 181 Esophagitis, 94, 103, 178, 181 Esophagus, 176, 178, 179, 181, 183, 190, 199, 205, 209 Essential Tremor, 135, 179 Estradiol, 20, 179 Estrogen, 55, 144, 179, 204, 207 Ethanol, 26, 88, 179 Ether, 4, 11, 13, 16, 64, 80, 90, 91, 92, 179 Ethnic Groups, 6, 179 Evacuation, 93, 172, 179, 189, 203 Excitatory, 25, 179 Exocrine, 169, 179, 196 Exogenous, 160, 179, 183, 198 External-beam radiation, 179, 188, 203, 215 Extracellular, 172, 177, 179, 208 Extracorporeal, 4, 5, 12, 13, 14, 16, 17, 38, 44, 50, 91, 111, 114, 179, 183, 190 Extraction, 7, 8, 13, 15, 17, 38, 87, 96, 179 F Facial, 179, 191 Family Planning, 131, 179 Fatty acids, 92, 96, 98, 99, 179, 182, 199, 202 Feces, 169, 172, 179, 210 Fetus, 179, 199, 201, 214 Fibril, 97, 179 Fibrin, 165, 179, 198, 211 Fibrosis, 83, 135, 179, 206 Filtration, 19, 179 Fistula, 19, 46, 179, 195 Fixatives, 173, 180 Flatus, 156, 180 Fluorescence, 23, 30, 31, 180 Fluorine, 88, 180 Flush, 89, 180 Fold, 9, 180 Foramen, 180, 191, 198 Fractionation, 28, 180 Fundus, 81, 180 Fungi, 172, 180, 192, 214 G Gallbladder Emptying, 34, 120, 180 Gallic Acid, 86, 180 Ganglia, 25, 159, 164, 180, 194, 198 Ganglion, 25, 180 Gas, 10, 156, 161, 164, 167, 169, 174, 175, 180, 185, 186, 187, 188, 195, 210

Gasoline, 80, 180 Gastric, 31, 82, 83, 163, 167, 180, 181, 183, 198 Gastric Acid, 82, 83, 180 Gastric Juices, 181, 198 Gastric Mucosa, 181, 198 Gastrin, 181, 185 Gastritis, 87, 181 Gastroenteritis, 166, 181 Gastroenterologist, 109, 181 Gastroesophageal Reflux, 45, 56, 181 Gastroesophageal Reflux Disease, 45, 56, 181 Gastrointestinal tract, 30, 87, 107, 108, 114, 179, 181, 208 Gelatin, 181, 182 Gels, 27, 181 Gene, 18, 19, 22, 30, 31, 100, 106, 136, 137, 160, 165, 181, 185, 188, 196 Generator, 91, 181 Genetic Code, 100, 181, 195 Genetic Techniques, 22, 181 Genetics, 21, 40, 114, 172, 182, 197 Genotype, 182, 199 Geriatric, 8, 182 Gestation, 20, 182, 199 Gland, 159, 182, 196, 202, 204, 207, 209, 211 Glucose, 14, 86, 96, 99, 118, 135, 168, 170, 175, 182, 183, 187, 204, 206 Glucose Intolerance, 175, 182 Glucose tolerance, 14, 86, 96, 182 Glucose Tolerance Test, 14, 182 Glycerol, 182, 199 Glycerophospholipids, 182, 199 Glycine, 26, 89, 164, 169, 170, 175, 182, 189 Glycoprotein, 19, 67, 82, 182, 193 Gonadal, 182, 209 Gout, 97, 182 Governing Board, 182, 201 Grade, 178, 182 Granulocytes, 182, 207 Groin, 183, 187 Growth, 27, 114, 135, 161, 162, 164, 168, 183, 191, 194, 195, 196, 200, 206, 208, 211, 213 Growth Inhibitors, 27, 183 Guanylate Cyclase, 183, 195 Guinea Pigs, 53, 183 H Haploid, 183, 200 Haptens, 160, 183, 204

222 Gallstones

Headache, 166, 183 Health Policy, 13, 183 Health Promotion, 113, 183 Heart attack, 167, 183 Heartburn, 103, 105, 156, 183, 184, 186 Heme, 12, 165, 174, 183 Hemodiafiltration, 183, 213 Hemodialysis, 43, 166, 175, 183, 213 Hemofiltration, 183, 213 Hemoglobin, 161, 169, 178, 183, 184, 209, 211 Hemoglobinuria, 135, 184 Hemolysis, 67, 184 Hemolytic, 184, 203, 211 Hemoptysis, 45, 184 Hemorrhage, 48, 177, 183, 184, 210 Hemostasis, 93, 184 Hepatic, 12, 15, 17, 23, 25, 29, 37, 41, 48, 54, 65, 68, 110, 171, 177, 182, 184, 190, 198, 208 Hepatic Duct, Common, 177, 184 Hepatitis, 39, 43, 87, 184 Hepatobiliary, 16, 22, 42, 105, 109, 110, 184 Hepatocellular, 23, 43, 184 Hepatocellular carcinoma, 43, 184 Hepatocyte, 23, 169, 184 Hepatoma, 23, 26, 184 Hereditary, 35, 100, 182, 184, 194, 205, 211 Heredity, 181, 182, 184 Heterozygote, 26, 184 Hiatal Hernia, 103, 184 Homeostasis, 20, 28, 29, 100, 101, 184 Homologous, 160, 184, 210 Hormonal, 20, 163, 185 Hormone Replacement Therapy, 144, 185 Host, 163, 179, 185, 186, 214 Hydrogen, 26, 78, 88, 159, 164, 167, 175, 185, 193, 195, 196, 202 Hydrogen Peroxide, 26, 185 Hydrolysis, 168, 185, 188, 199, 200 Hydrophobic, 24, 26, 182, 185, 189 Hyperbilirubinemia, 48, 185, 188 Hypercholesterolemia, 28, 30, 69, 85, 86, 96, 97, 99, 118, 185 Hyperglycemia, 98, 185 Hyperlipidemia, 9, 20, 99, 185 Hyperlipoproteinemia, 185 Hypersensitivity, 160, 175, 185 Hypertension, 39, 43, 86, 97, 98, 99, 163, 167, 183, 185, 195, 213 Hypertriglyceridemia, 99, 185 Hyperuricemia, 182, 185

Hypothalamus, 185, 208 I Id, 59, 69, 141, 146, 147, 152, 154, 185 Ileal, 18, 54, 185 Ileum, 185, 188 Ileus, 11, 31, 108, 110, 185 Imidazole, 98, 186 Immune response, 162, 163, 183, 186, 210, 214 Immunity, 33, 186, 196 Immunodeficiency, 135, 186 Immunofluorescence, 35, 186 Immunogenic, 186, 204 Immunohistochemistry, 25, 186 Immunotherapy, 175, 186 Impairment, 100, 163, 169, 176, 186, 192 Implant radiation, 186, 187, 188, 203, 215 In situ, 79, 80, 110, 186 In vitro, 23, 24, 42, 55, 63, 64, 66, 186, 212 In vivo, 19, 23, 26, 88, 91, 186 Incision, 90, 93, 114, 186, 187 Incisional, 11, 186 Incompetence, 181, 186 Indicative, 104, 186, 197, 214 Indigestion, 103, 105, 155, 186, 201 Induction, 24, 26, 57, 89, 186, 208 Infarction, 173, 186, 192, 194 Infection, 7, 17, 33, 43, 84, 109, 114, 181, 186, 190, 210 Inflammation, 6, 10, 24, 34, 162, 163, 169, 171, 178, 179, 181, 184, 186, 187, 197, 198, 211, 214 Inflammatory bowel disease, 109, 187 Infusion, 11, 19, 80, 85, 90, 92, 187 Ingestion, 83, 166, 169, 180, 182, 187, 200 Inguinal, 42, 187 Inguinal Hernia, 42, 187 Initiation, 40, 187 Inorganic, 12, 159, 187, 193 Insight, 20, 187 Instillation, 13, 187 Insufflation, 89, 187 Insulin, 22, 98, 182, 187 Insulin-dependent diabetes mellitus, 187 Intermittent, 80, 98, 121, 187 Internal Medicine, 6, 8, 13, 27, 52, 53, 56, 181, 187 Internal radiation, 187, 188, 203, 215 Interstitial, 165, 187, 188, 215 Intestinal, 12, 27, 29, 43, 89, 103, 105, 169, 175, 182, 187, 191

Index 223

Intestine, 19, 27, 83, 87, 164, 165, 178, 187, 189, 198 Intoxication, 187, 215 Intracellular, 18, 25, 166, 181, 186, 187, 191, 195, 201, 202, 206, 207 Intracellular Membranes, 18, 187, 191 Intramuscular, 187, 197 Intraperitoneal, 48, 187 Intravenous, 7, 13, 187, 197 Invasive, 7, 35, 81, 93, 95, 143, 186, 187, 190 Involuntary, 164, 179, 188, 194 Iodine, 53, 88, 188 Ion Channels, 188, 195 Ion Transport, 28, 188 Ions, 164, 169, 177, 185, 188, 192 Irradiation, 26, 188, 215 Irrigation, 89, 93, 188 Irritable Bowel Syndrome, 94, 188 Ischemia, 86, 97, 101, 163, 188 Isopropyl, 92, 188 Isozymes, 188, 203 J Jaundice, 41, 82, 84, 90, 103, 108, 114, 144, 156, 185, 188 Jejunum, 169, 188 K Kb, 130, 188 Kidney Disease, 76, 114, 130, 135, 141, 145, 146, 189 Kidney stone, 97, 189, 213 Kinetic, 80, 189, 198 L Laparoscopy, 38, 79, 143, 189 Large Intestine, 176, 187, 189, 205, 208 Laxative, 101, 160, 169, 189 Length of Stay, 108, 189 Lens, 167, 189 Lenticular, 98, 189 Leptin, 25, 189 Leukemia, 26, 135, 189 Library Services, 152, 189 Life Expectancy, 8, 189 Ligament, 189, 202 Ligands, 23, 189 Ligation, 24, 189 Linkage, 22, 168, 189, 199 Lip, 100, 189 Lipopolysaccharide, 30, 189 Lipoprotein, 18, 86, 97, 189, 190 Lithocholic Acid, 89, 189 Lithotripsy, Laser, 17, 190

Liver Cirrhosis, 48, 190 Liver scan, 190, 206 Lobe, 94, 100, 190 Localization, 186, 190 Localized, 22, 90, 91, 159, 175, 186, 190, 200, 213 Lovastatin, 56, 190, 208 Low-calorie diet, 145, 190 Low-density lipoprotein, 86, 97, 189, 190 Lower Esophageal Sphincter, 181, 190 Lumen, 95, 166, 190 Lymphatic, 178, 186, 190, 209 Lymphoid, 162, 190 Lymphoma, 135, 190 M Magnetic Resonance Imaging, 16, 190, 206 Malabsorption, 69, 103, 135, 191 Malformation, 25, 191 Malignant, 34, 135, 159, 163, 191, 194, 204 Malnutrition, 163, 191, 194 Mammary, 191, 204 Mammogram, 166, 191, 192 Meat, 191, 206 Meatus, 81, 191 Medial, 163, 191 Mediate, 25, 191 Mediator, 169, 191 Medicament, 101, 191 MEDLINE, 131, 134, 135, 191 Melanocytes, 191 Melanoma, 135, 191 Membrane Microdomains, 23, 191 Membrane Proteins, 168, 191 Memory, 174, 191 Menopause, 20, 55, 191, 201 Menstrual Cycle, 192, 201 Menstruation, 160, 191, 192, 196 Mental Disorders, 76, 192 Mental Health, iv, 17, 76, 130, 133, 192, 203 Mentors, 21, 192 Meta-Analysis, 86, 97, 192 Metabolic disorder, 43, 182, 192 Metabolite, 190, 192, 199 MI, 15, 157, 192 Micelles, 89, 192 Microbe, 192, 212 Microcalcifications, 166, 192 Microcirculation, 190, 192 Microorganism, 171, 192, 214 Micro-organism, 175, 183, 192

224 Gallstones

Microscopy, 16, 23, 27, 28, 30, 31, 49, 173, 192 Microspheres, 82, 83, 192 Microtubules, 23, 192 Migration, 95, 192 Mitochondria, 26, 99, 192, 196 Mitosis, 100, 162, 193 Mobilization, 25, 193 Modeling, 8, 176, 193 Modification, 62, 193, 203 Modulator, 99, 193 Molecular, 18, 20, 22, 27, 97, 131, 133, 134, 165, 172, 176, 183, 193, 213 Molecule, 27, 99, 162, 164, 171, 177, 178, 185, 193, 196, 204, 207 Monitor, 34, 84, 93, 193, 195 Monoclonal, 188, 193, 203, 215 Morphology, 27, 53, 193 Motility, 12, 23, 25, 30, 43, 47, 49, 120, 193 Motion Sickness, 193, 194 Mucinous, 180, 193 Mucolytic, 159, 193 Mucoproteins, 78, 193 Mucosa, 41, 80, 169, 181, 193 Mucus, 164, 193 Multiparous, 25, 193 Muscle Fibers, 193, 194 Muscle tension, 25, 193 Muscular Atrophy, 135, 194 Muscular Dystrophies, 176, 194 Myocardial Ischemia, 161, 194 Myocardium, 161, 192, 194 Myotonic Dystrophy, 135, 194 N Nausea, 82, 104, 114, 121, 144, 156, 181, 186, 194, 195, 201, 213 NCI, 1, 76, 129, 170, 194, 197 Necrosis, 162, 186, 192, 194 Need, 3, 80, 83, 85, 103, 107, 108, 113, 121, 125, 132, 145, 148, 160, 170, 194, 212 Neoplasia, 135, 194 Neoplasm, 194, 213 Neoplastic, 19, 190, 194 Nephropathy, 189, 194 Nerve, 100, 161, 163, 175, 180, 191, 194, 201, 206, 209, 212 Nervous System, 101, 135, 160, 168, 191, 194, 198 Networks, 67, 194 Neurodegenerative Diseases, 100, 164, 194 Neuromuscular, 25, 159, 194, 213 Neurons, 25, 175, 179, 180, 194, 195, 210

Neurotransmitters, 25, 195 Neutrons, 188, 195, 203 Niacin, 99, 195 Nitric Oxide, 30, 195 Nonulcer Dyspepsia, 103, 195 Nuclear, 21, 23, 58, 164, 172, 177, 180, 194, 195 Nuclei, 172, 177, 190, 193, 195, 202 Nucleic acid, 164, 181, 195 Nucleus, 96, 100, 101, 162, 164, 170, 173, 174, 175, 189, 195, 202, 211 O Octreotide, 109, 118, 195 Ocular, 98, 195 Odds Ratio, 195, 205 Office Management, 110, 111, 195 Oligomenorrhea, 196, 200 Omega-3 fatty acid, 99, 196 Oncogene, 135, 196 Opacity, 167, 175, 196 Oral Dissolution Therapy, 11, 13, 111, 196 Organ Culture, 196, 212 Organelles, 173, 174, 191, 196 Orthostatic, 195, 196 Osteoporosis, 196, 204 Ovaries, 196, 200, 207 Ovary, 173, 179, 196 Overexpress, 23, 196 Overweight, 9, 25, 36, 54, 59, 65, 121, 144, 145, 196 Ovum, 173, 182, 196, 201, 215 Oxidation, 98, 159, 174, 196 P Palate, 196, 208, 214 Palliative, 196, 211 Pancreas, 6, 107, 159, 176, 181, 187, 196, 197, 208 Pancreatic, 40, 42, 47, 70, 103, 135, 140, 167, 169, 177, 178, 181, 196, 197 Pancreatic cancer, 40, 47, 135, 196 Pancreatic Ducts, 178, 196 Pancreatic Juice, 181, 196, 197 Pancreatitis, 6, 7, 8, 10, 12, 13, 17, 40, 50, 70, 82, 84, 90, 108, 110, 114, 118, 120, 197 Papilla, 36, 177, 197 Parenteral, 85, 109, 197 Parenteral Nutrition, 85, 109, 197 Paroxysmal, 135, 161, 197 Particle, 197, 208, 212 Patch, 25, 197 Pathogenesis, 12, 15, 17, 18, 20, 21, 24, 25, 28, 46, 47, 48, 57, 65, 107, 109, 111, 197

Index 225

Pathologic, 162, 165, 173, 180, 185, 197, 203 Pathologic Processes, 162, 197 Pathologies, 97, 197 Pathophysiology, 5, 18, 105, 107, 110, 197 Patient Education, 115, 142, 144, 145, 150, 152, 157, 197 Patient Selection, 6, 13, 197 PDQ, 141, 197 Pelvic, 197, 202 Penis, 100, 197 Pepsin, 198 Pepsin A, 198 Peptic, 103, 198 Peptic Ulcer, 103, 198 Peptide, 169, 189, 198, 200, 202, 212 Percutaneous, 7, 8, 12, 13, 14, 17, 38, 46, 81, 92, 109, 110, 190, 198 Percutaneous transhepatic cholangiography, 7, 198 Perforation, 110, 162, 180, 198 Peripheral Nervous System, 194, 198, 208, 210 Peristalsis, 30, 198 Peritoneal, 36, 107, 187, 198, 210 Peritoneal Cavity, 187, 198, 210 Peritoneum, 198 Peritonitis, 110, 198 Petroleum, 180, 198 Pharmaceutical Preparations, 168, 179, 181, 198 Pharmacokinetics, 176, 198 Pharmacologic, 161, 199, 212 Pharynx, 181, 199 Phenotypes, 20, 21, 22, 199 Phosphatidic Acids, 199 Phosphatidylcholines, 23, 199 Phospholipases, 199, 207 Phospholipids, 45, 66, 89, 179, 189, 199 Phosphorus, 62, 166, 199 Phosphorylate, 99, 199 Phosphorylation, 99, 159, 199, 203 Photodynamic therapy, 26, 199 Photosensitizing Agents, 26, 199 Physical Examination, 111, 199 Physiologic, 160, 165, 175, 192, 199, 202, 204 Physiology, 58, 103, 110, 181, 199 Pilot study, 26, 57, 199 Placenta, 179, 199, 201 Plague, 17, 199 Plant Growth Regulators, 183, 200 Plant sterols, 64, 66, 200

Plants, 167, 169, 170, 182, 193, 200, 206, 212 Plaque, 88, 200 Plasma, 19, 23, 86, 97, 98, 99, 162, 168, 169, 181, 182, 184, 185, 200, 207 Platelet Activation, 200, 208 Platelet Aggregation, 195, 200 Platelets, 195, 200, 211 Ploidy, 35, 200 Pneumonitis, 94, 166, 200 Poisoning, 166, 169, 181, 187, 194, 200 Polycystic, 98, 135, 200 Polycystic Ovary Syndrome, 98, 200 Polypeptide, 161, 171, 198, 200, 208, 211 Polysaccharide, 162, 168, 200 Polyvalent, 177, 200 Port, 47, 84, 89, 200, 201 Port-a-cath, 200, 201 Postcholecystectomy Syndrome, 11, 12, 201 Posterior, 161, 163, 164, 176, 196, 201, 214 Postmenopausal, 118, 196, 201, 204 Postoperative, 5, 13, 15, 46, 201 Postprandial, 20, 201 Postsynaptic, 201, 207, 210 Potassium, 78, 201 Potentiation, 201, 207 Practicability, 201, 212 Practice Guidelines, 133, 146, 201 Precipitation, 12, 66, 201 Precursor, 20, 64, 162, 170, 177, 178, 201, 214 Prenatal, 20, 67, 177, 201 Prevalence, 5, 6, 9, 14, 19, 22, 24, 38, 41, 43, 57, 119, 178, 195, 201 Progeny, 172, 201 Progesterone, 20, 201, 209 Progression, 43, 161, 201, 213 Progressive, 163, 168, 170, 174, 183, 194, 200, 201, 213 Prone, 26, 50, 201 Prone Position, 50, 201 Prophylaxis, 85, 86, 96, 97, 202 Proportional, 86, 97, 202 Prospective study, 46, 50, 202 Prostaglandin, 66, 202 Prostaglandins A, 202 Prostate, 135, 202 Protein C, 161, 162, 163, 170, 189, 202 Protein S, 106, 110, 135, 136, 165, 178, 181, 202, 206 Protons, 185, 202, 203

226 Gallstones

Protozoa, 172, 192, 202, 214 Proximal, 84, 176, 203 Psoriasis, 199, 203 Psyllium, 73, 203 Puberty, 20, 203 Public Health, 5, 52, 58, 106, 133, 145, 203 Public Policy, 131, 203 Publishing, 6, 13, 30, 53, 107, 108, 203 Pulmonary, 165, 169, 173, 183, 203 Pulmonary Edema, 169, 203 Pulse, 193, 203 Purgative, 189, 203 Pyruvate Kinase, 35, 203 Q Quality of Life, 108, 203, 210 Quaternary, 82, 203 R Race, 192, 203 Radiation, 161, 178, 179, 180, 187, 188, 199, 203, 204, 206, 215 Radiation therapy, 179, 180, 187, 188, 203, 215 Radioactive, 165, 185, 186, 187, 188, 190, 195, 203, 204, 206, 215 Radiography, 6, 169, 204 Radioimmunoassay, 25, 204 Radiolabeled, 188, 203, 204, 215 Radiological, 140, 198, 204 Radiologist, 109, 204 Radiology, 12, 45, 57, 64, 66, 110, 140, 204 Radiolucent, 10, 204 Radiopharmaceutical, 181, 204 Radiotherapy, 165, 188, 204, 215 Raloxifene, 99, 204, 207 Randomized, 49, 50, 57, 177, 204 Reabsorption, 178, 204 Reactive Oxygen Species, 24, 204 Reagent, 169, 180, 204 Receptor, 20, 23, 24, 25, 41, 57, 99, 162, 204, 207 Recombination, 172, 204 Rectum, 162, 165, 171, 176, 180, 187, 189, 202, 205 Recuperation, 80, 205 Recur, 14, 143, 205 Recurrence, 5, 7, 8, 14, 17, 96, 118, 205 Red blood cells, 178, 184, 205, 206, 208, 209 Red Nucleus, 163, 205 Reductase, 99, 190, 205, 208 Refer, 1, 171, 180, 190, 195, 205 Reflux, 87, 141, 181, 205

Refraction, 205, 209 Refractory, 177, 205 Regimen, 177, 205 Regurgitation, 181, 183, 205 Relative risk, 4, 205 Remission, 205 Renal pelvis, 189, 205 Respiration, 167, 193, 205 Retinoblastoma, 135, 205 Retrograde, 13, 90, 140, 205 Ribosome, 206, 212 Risk factor, 4, 5, 7, 15, 20, 22, 30, 32, 48, 52, 86, 96, 107, 114, 118, 121, 132, 144, 202, 205, 206 Risk patient, 7, 206 Rod, 164, 170, 206 S Salivary, 176, 196, 206 Salivary glands, 176, 206 Saponins, 206, 209 Saturated fat, 96, 206 Scans, 12, 206 Schizoid, 206, 215 Schizophrenia, 206, 215 Schizotypal Personality Disorder, 206, 215 Sclerosis, 81, 135, 163, 206 Screening, 22, 97, 170, 197, 206 Second Messenger Systems, 195, 206 Secretion, 12, 17, 18, 20, 23, 29, 54, 57, 110, 187, 193, 195, 206, 207 Secretory, 18, 207, 210 Sedentary, 6, 207 Seizures, 197, 207 Selective estrogen receptor modulator, 204, 207 Semen, 202, 207 Semisynthetic, 174, 207 Senile, 100, 196, 207 Sequencing, 21, 207 Serum, 17, 20, 26, 30, 58, 62, 99, 100, 101, 118, 171, 190, 198, 204, 207 Serum Albumin, 204, 207 Sex Characteristics, 203, 207, 211 Sex Determination, 135, 207 Shock, 4, 5, 10, 12, 13, 14, 16, 17, 38, 44, 50, 101, 110, 111, 145, 190, 207, 212 Side effect, 4, 80, 123, 125, 160, 185, 207, 210, 212 Signal Transduction, 25, 168, 207 Signs and Symptoms, 16, 132, 205, 208, 213 Simvastatin, 37, 65, 208

Index 227

Skeletal, 99, 170, 194, 208 Skeleton, 202, 208 Sludge, 20, 35, 85, 94, 109, 208 Small intestine, 164, 169, 170, 173, 176, 178, 185, 187, 188, 201, 208 Smooth muscle, 25, 166, 208, 210 Snoring, 101, 208 Social Environment, 203, 208 Sodium, 29, 78, 101, 182, 204, 208 Solvent, 52, 61, 67, 80, 88, 90, 92, 110, 169, 179, 182, 208 Somatostatin, 25, 195, 208 Sound wave, 143, 204, 208, 213 Spasmolytic, 87, 208 Spastic, 188, 208 Specialist, 147, 208 Species, 176, 181, 183, 192, 193, 203, 204, 208, 210, 212, 213, 214, 215 Specificity, 16, 160, 209 Spectrum, 5, 26, 209 Spherocytes, 209 Spherocytosis, 35, 209 Sphincter, 89, 95, 110, 180, 209 Spinal cord, 33, 39, 49, 168, 169, 180, 194, 198, 209 Spleen, 190, 209 Splenectomy, 35, 209 Sporadic, 194, 205, 209 Staging, 206, 209 Stagnation, 81, 209 Standard therapy, 13, 209 Stasis, 17, 24, 25, 85, 209 Steel, 170, 209 Steroid, 57, 164, 206, 208, 209 Stimulant, 166, 209 Stimulus, 173, 176, 177, 188, 209, 211 Stool, 188, 189, 210 Stress, 167, 181, 188, 194, 210 Stroke, 58, 76, 101, 130, 167, 210 Structure-Activity Relationship, 26, 210 Stump, 100, 210 Subacute, 186, 210 Subclinical, 186, 207, 210 Subcutaneous, 159, 177, 197, 210 Subhepatic, 46, 47, 210 Substance P, 178, 192, 207, 210 Substrate, 28, 99, 210 Suction, 17, 93, 179, 210 Supplementation, 62, 67, 210 Supportive care, 197, 210 Suppurative, 110, 210 Symbiosis, 5, 210

Symphysis, 202, 210 Synapses, 195, 210 Synaptic, 207, 210 Synergistic, 86, 97, 211 Systemic, 124, 162, 165, 186, 188, 203, 211, 215 Systolic, 185, 211 T Taurine, 19, 26, 73, 89, 164, 169, 170, 175, 189, 211 Telangiectasia, 135, 211 Temporal, 191, 211 Testis, 179, 211 Testosterone, 205, 211 Thalamic, 163, 211 Thalamic Diseases, 163, 211 Thalassemia, 48, 211 Therapeutics, 41, 47, 50, 124, 211 Thorax, 159, 211 Threshold, 19, 26, 185, 211 Thrombophlebitis, 11, 211 Thrombosis, 202, 210, 211 Thrombus, 173, 186, 194, 200, 211 Thyroid, 188, 211 Tin, 26, 211 Tissue Culture, 23, 211 Tolerance, 159, 182, 212 Tomography, 36, 212 Tonicity, 184, 212 Topical, 3, 5, 179, 185, 212 Toxic, iv, 19, 83, 91, 92, 98, 172, 178, 186, 199, 212 Toxicity, 19, 83, 176, 212 Toxicology, 132, 212 Toxins, 162, 186, 212 Trace element, 170, 180, 211, 212 Traction, 170, 212 Transduction, 207, 212 Transfection, 165, 212 Translation, 107, 178, 212 Translocation, 27, 178, 212 Transmitter, 79, 159, 188, 191, 210, 212 Transplantation, 170, 212 Trauma, 95, 164, 178, 183, 194, 197, 211, 212 Treatment Outcome, 15, 212 Triage, 12, 212 Trifluoroacetic Acid, 101, 212 Triglyceride, 86, 97, 98, 185, 213 Tuberculosis, 173, 213 Tuberous Sclerosis, 135, 213 Tubulin, 192, 213

228 Gallstones

Tumor model, 26, 213 Tumour, 180, 213 U Ulcer, 195, 198, 213 Ultrafiltration, 19, 183, 213 Ultrasonography, 6, 7, 13, 15, 16, 22, 140, 213 Ultrasound test, 52, 94, 213 Unconscious, 185, 213 Uraemia, 197, 213 Ureter, 190, 205, 213 Urethra, 197, 202, 213, 214 Uric, 182, 185, 213 Urinary, 165, 166, 190, 213 Urine, 156, 165, 176, 184, 189, 205, 213, 214 Ursodeoxycholic Acid, 5, 13, 26, 57, 78, 83, 86, 89, 214 Uterus, 173, 180, 192, 196, 201, 214 Uvula, 208, 214 V Vaccines, 214 Vagina, 175, 192, 214 Vascular, 85, 88, 96, 98, 100, 178, 186, 190, 192, 195, 199, 211, 214 Vasculitis, 197, 214

Vasodilator, 30, 166, 214 Vegetarianism, 66, 214 Vein, 187, 195, 211, 214 Venous, 202, 214 Ventricular, 177, 214 Ventricular Dysfunction, 177, 214 Venules, 165, 167, 192, 214 Vertebrae, 209, 214 Veterinary Medicine, 131, 214 Viral, 159, 212, 214 Virulence, 212, 214 Virus, 43, 163, 200, 212, 214 Viscosity, 45, 80, 92, 159, 214 Vitro, 214 Vivo, 88, 91, 214 W Watchful waiting, 8, 144, 214 Withdrawal, 92, 215 X Xenograft, 161, 213, 215 X-ray, 7, 156, 172, 177, 178, 180, 188, 191, 195, 198, 203, 204, 206, 215 X-ray therapy, 188, 215 Z Zygote, 172, 215

Index 229

230 Gallstones

Index 231

232 Gallstones