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

FLUCONAZOLE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Fluconazole: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00435-6 1. Fluconazole-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 fluconazole. 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 FLUCONAZOLE.......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Fluconazole ................................................................................... 8 E-Journals: PubMed Central ....................................................................................................... 27 The National Library of Medicine: PubMed ................................................................................ 43 CHAPTER 2. NUTRITION AND FLUCONAZOLE ................................................................................ 91 Overview...................................................................................................................................... 91 Finding Nutrition Studies on Fluconazole .................................................................................. 91 Federal Resources on Nutrition ................................................................................................... 96 Additional Web Resources ........................................................................................................... 96 CHAPTER 3. ALTERNATIVE MEDICINE AND FLUCONAZOLE ......................................................... 99 Overview...................................................................................................................................... 99 National Center for Complementary and Alternative Medicine.................................................. 99 Additional Web Resources ......................................................................................................... 106 General References ..................................................................................................................... 107 CHAPTER 4. DISSERTATIONS ON FLUCONAZOLE ......................................................................... 109 Overview.................................................................................................................................... 109 Dissertations on Fluconazole ..................................................................................................... 109 Keeping Current ........................................................................................................................ 109 CHAPTER 5. PATENTS ON FLUCONAZOLE .................................................................................... 111 Overview.................................................................................................................................... 111 Patents on Fluconazole .............................................................................................................. 111 Patent Applications on Fluconazole........................................................................................... 116 Keeping Current ........................................................................................................................ 122 CHAPTER 6. BOOKS ON FLUCONAZOLE ........................................................................................ 123 Overview.................................................................................................................................... 123 Chapters on Fluconazole ............................................................................................................ 123 CHAPTER 7. PERIODICALS AND NEWS ON FLUCONAZOLE .......................................................... 125 Overview.................................................................................................................................... 125 News Services and Press Releases.............................................................................................. 125 Academic Periodicals covering Fluconazole............................................................................... 127 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 129 Overview.................................................................................................................................... 129 U.S. Pharmacopeia..................................................................................................................... 129 Commercial Databases ............................................................................................................... 130 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135 Other Commercial Databases..................................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Finding Associations.................................................................................................................. 142 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 145 Overview.................................................................................................................................... 145 Preparation................................................................................................................................. 145 Finding a Local Medical Library................................................................................................ 145 Medical Libraries in the U.S. and Canada ................................................................................. 145

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ONLINE GLOSSARIES................................................................................................................ 151 Online Dictionary Directories ................................................................................................... 151 FLUCONAZOLE DICTIONARY ................................................................................................ 153 INDEX .............................................................................................................................................. 205

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with fluconazole 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 fluconazole, 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 fluconazole, 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 fluconazole. 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 fluconazole, 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 fluconazole. 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 FLUCONAZOLE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on fluconazole.

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

Candidiasis: Pathogenesis, Clinical Characteristics, and Treatment Source: CDA Journal. Journal of the California Dental Association. 28(12): 942-948. December 2000. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: Candida organisms live on the skin and mucous membranes of up to 75 percent of the population. They can live commensally without causing harm or can change to an aggressive form and invade tissue, causing both acute and chronic disease in the host. This article discusses the pathogenesis of candidiasis, the clinical characteristics of oral infection, local and systemic factors that predispose to infection, and treatment. Oropharyngeal candidiasis manifests clinically as acute

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Fluconazole

pseudomembranous lesions, acute atrophic lesions, chronic atrophic lesions, chronic hypertrophic or hyperplastic lesions, and angular cheilitis. Systemic infection leading to candidemia can be devastating and cause up to a 60 percent mortality rate in medical or post surgical intensive care wards. Oral nystatin, clotrimazole, and fluconazole usually provide appropriate therapy, although resistance to medications is increasing, particularly in immunocompromised hosts. 8 figures. 1 table. 53 references. •

Antifungal Agents and Their Renal Implications in the Neonate Source: Journal of Perinatal and Neonatal Nursing. 8(1): 59-73. June 1994. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, P.O. Box 990, Frederick, MD 21701-9782. (800) 638-8437. Fax (301) 695-7931. Summary: In this article, the authors discuss antifungal agents and their renal implications in the neonate. The authors note that the incidence of superficial or systemic fungal infections has been increasing in neonates. The cause of this increased susceptibility to fungal infections is due to the increased use of mechanical ventilation, indwelling catheters, broad-spectrum antibiotic therapy, parenteral nutrition, and steroid therapy. The authors discuss the etiology, signs, symptoms, diagnosis, and treatment of the usual neonatal fungal infections. Each of the antifungal agents used to treat neonates is discussed with regard to its mechanism of action, pharmacokinetics, indications, normal and renal functional impairment dosing, and adverse effects. Antifungal agents covered are amphotericin B, clotrimazole, flucytosine, fluconazole, itraconazole, ketoconazole, miconazole, and nystatin. 2 tables. 25 references. (AA-M).

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Identification of Candida Dubliniensis in a Study of HIV-Seropositive Pediatric Dental Patients Source: Pediatric Dentistry. 22(3): 234-238. May-June 2000. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2616. Summary: Oral fungal colonization remains one of the most common opportunistic infections observed in both adult and pediatric HIV-infected patients. Although Candida albicans is the most frequently isolated opportunistic fungal species, a recently characterized Candida species, C. dubliniensis, has gained attention due to its almost exclusive association with HIV-seropositive individuals. This article reports on a study undertaken to prospectively screen for the presence of C. dubliniensis among pediatric HIV-positive patients. Oral samples taken from 27 children were cultured for the presence of yeast. Among the 27 patients tested, 3 patients were found to harbor C. dubliniensis, one of which also grew C. glabrata; 12 patients were colonized with C. albicans, while the remaining 12 patients were negative for yeast. All three C. dubliniensis isolates were found to be susceptible to fluconazole. These results confirm the presence of this novel species in a dental pediatric HIV-seropositive population and supports the need for further investigation into the prevalence and pathogenesis of C. dubliniensis. 1 figure. 30 references.

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Epidemiology of Non-Albicans Candida in Oropharyngeal Candidiasis in HIV Patients Source: SCD. Special Care in Dentistry. 20(5): 178-181. September-October 2000. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824.

Studies

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Summary: Oropharyngeal candidiasis (OPC) is the most common fungal infection in patients with HIV infection. The most common organism isolated in OPC is C. albicans, however, this article explores the epidemiology (causes) of non-albicans Candida in oropharyngeal candidiasis in HIV patients. Fluconazole has been proven to be very effective in treating this infection, but decreased susceptibility of Candida to this drug has emerged. Certain non-albicans species such as C. glabrata and C. krusei are commonly less susceptible to fluconazole that C. albicans and are being isolated with increased frequency in HIV patients. The authors report on a study undertaken to determine if the presence of non-albicans Candida with OPC in HIV patients had an impact on clinical presentation. The results show that late stage HIV patients have a high prevalence of Candida with decreased susceptibility to fluconazole, especially non-albicans species. OPC episodes with non-albicans isolates were more likely to require higher doses of fluconazole to achieve clinical care. Also, the presence of nonalbicans Candida was more frequently associated with severe symptoms. 4 figures. 1 table. 17 references. •

Management of Candiduria Source: Current Urology Reports. 2(4): 321-325. August 2001. Contact: Current Science, Inc. 400 Market Street, Suite 700, Philadelphia, PA 19106 (800) 427-1796. Fax (215) 574-2225. E-mail: [email protected]. Website: http://www.current-reports.com. Summary: The distinction between Candida colonization of the urinary tract and infection is often blurred. This review article summarizes the diagnosis and management of candiduria (presence of the fungal species candida in the urine). Asymptomatic candiduria is particularly common in catheterized intensive care patients. To date, few studies have addressed the appropriate treatment regimens for candiduria. Fluconazole has become a mainstay of therapy; however, when to treat, whom to treat, and how long to treat are still largely unanswered questions. Asymptomatic nosocomial candiduria infrequently requires treatment intervention because morbidity is low and ascending infection and candidemia are rare complications. An understanding of the anatomic site of infection drives treatment decisions. More research is needed to define diagnostic criteria and therapeutic pathways. 1 table. 32 references.

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Preventing Illness: Peace of Mind Through Prophylaxis Source: Positively Aware; Fall 1993. Contact: Test Positive Aware Network, 5537 N Broadway, Chicago, IL, 60640, (773) 9899400, http://www.tpan.com. Summary: This article discusses prophylaxis and HIV-related illnesses, beginning with an explanation of CD4 lymphocytes and how the CD4 cell count determines when prophylactic treatment should begin. The prophylactic drugs examined include Septra or Bactrim for Pneumocystis carinii pneumonia (PCP), with Dapsone as an alternative. Septra is also indicated for toxoplasmosis, while Mycobutin is used for Mycobacterium avium complex (MAC); Fluconazole, for candidiasis; and Izoniazid, for tuberculosis (TB). In each case, the infections themselves are discussed as well as possible side effects from the treatments. Also, routine vaccinations are also recommended for HIV-positive persons. Prophylactic treatments do not mean infections will not occur.

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Fluconazole

Nonreflux-Related Inflammatory Esophageal Conditions Source: Current Opinion in Gastroenterology. 8(4): 579-582. August 1992. Summary: This article discusses recent advances in nonreflux-related inflammatory esophageal conditions. The article reviews infectious diseases and the esophagus, including AIDS and HIV complex, esophageal tuberculosis, and the postpolio syndrome; drug-induced esophageal lesions; and other inflammatory conditions, including Behcet's disease, antracosis, and esophageal lichen planus. The author focuses on drug therapy for patients with AIDS and inflammatory esophageal conditions, concluding that fluconazole is probably a good candidate for prophylaxis of relapse but that further research is needed. 2 tables. 26 annotated references. (AA-M).

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Candida Infections of the Oropharynx and GI Tract: Pathogenesis, Prevention, Treatment Source: Practical Gastroenterology. 16(5): 10-11, 14-16, 18-19. May 1992. Summary: This article discusses the pathogenesis, prevention, and treatment of candida infections of the oropharynx and gastrointestinal (GI) tract. Topics include the organism itself, host defense factors and immune system diseases, diagnostic features of candidiasis, clinical studies of candidiasis therapy in four groups of patients (patients with cancer, patients for whom candida prophylaxis is appropriate, HIV-infected persons, and newborns), and resistance and invasive infection. The author considers the development of effective oral antifungal therapy (eg, ketoconazole and fluconazole), noting some of the complications that can arise with such therapy. 28 references.

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Systematic Review of the Effectiveness of Antifungal Drugs for the Prevention and Treatment of Oropharyngeal Candidiasis in HIV-positive Patients Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 92(2): 170-179. August 2001. Contact: Available from Mosby, Inc. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Website: www.harcourthealth.com. Summary: This article reports on a systematic review of randomized clinical trials (published between 1966 and 2000) that was undertaken to determine the strength of evidence for the effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B, fluconazole, ketoconazole, and itraconazole) to prevent and treat oral candidiasis (thrush, a fungal infection) in patients who are HIV positive. The automated database search identified 366 articles; six met inclusion and exclusion criteria with respect to prophylaxis (prevention), and 12 met criteria for treatment of oral candidiasis. The results showed that evidence for the prophylactic effectiveness of fluconazole is good, although insufficient to draw conclusions about the other antifungals. Evidence for treatment effectiveness is insufficient for amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole, and itraconazole. The authors also offer suggestions for strengthening the evidence base: use of larger, more well defined groups; control for immunologic status; viral load; history of oral candidiasis; past exposure to antifungals; baseline oral Candida carriage; drug interactions; and antiretroviral therapy; and consistent use of compliance monitors, fungal speciation, and susceptibility testing. 3 tables. 33 references.

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Oral Candidosis Source: Quintessence International. 33(7): 521-532. July-August 2002.

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Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. Summary: This article reviews clinical practice guidelines for oral candidosis, the most common opportunistic fungal infection encountered in dentistry. Normally a benign inhabitant of mucous membranes, the fungal organism Candida albicans, may present serious, even life-threatening infection in specific patient populations. As an opportunistic organism, C. albicans is extremely responsive to any process resulting in immunosuppression. The clinical manifestations of oral candidosis are variable, occasionally complicating the clinical diagnosis and management. Treatment is often initially rendered based on a provisional clinical diagnosis and supplemented with diagnostic laboratory tests. Specific treatments should be tailored to the individual patient, based on the current health status of the patient and the clinical presentation and severity of the infection. Appended to the article are five summaries of potential drug therapy for candidosis, covering the indications, contraindications, drug interactions, administration, efficacy, toxicity, length of treatment, cessation of treatment, and instructions to the patient for itraconazole, fluconazole, ketoconazole, clotrimazole, and nystatin. 4 figures. 2 tables. 44 references. •

Fungal Infections Commonly Found in Individuals With HIV/AIDS Source: STEP Perspective; Vol. 4, No. 2. Contact: Seattle Treatment Education Project, 1123 E John St, Seattle, WA, 98102, (206) 329-4857, http://www.thebody.com/step/steppage.html. Summary: This article reviews fungal infections commonly found in symptomatic HIV infection, focusing on those caused by Candida albicans and Cryptococcus neoformans. The discussion on candidiasis examines the manifestations, diagnoses, and treatments for oropharyngeal candidiasis, or thrush, Candida esophagitis, and vaginal candidiasis. The use of topical agents such as nystatin and clotrimazole is suggested for treating thrush and vaginal candidiasis, in addition to miconazole for the latter. The systemic agents ketaconazole and fluconazole are recommended for severe cases of oropharyngeal and vaginal candidiasis, and Candida esophagitis. A section on cryptococcosis emphasizes cryptococcal meningitis, referring to the often-subtle symptoms, tests available for diagnoses, and aspects of treatment with fluconazole or Amphotericin-B.

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Review of Oral Fungal Infections and Appropriate Therapy Source: JADA. Journal of the American Dental Association. 126(1): 63-72. January 1995. Summary: This article reviews oral fungal infections and the therapeutic options for each. The authors emphasize that dental health care providers must recognize oral fungal pathogens that often are markers for early signs of immune deterioration. Topics covered include localized fungal infections, including the various types of oral candidiasis; deep-seated fungal infections, including aspergillosis, cryptococcosis, histoplasmosis, geotrichosis, blastomycosis, and mucormycosis; diagnostic considerations for these deep-seated fungal infections; antifungal medications; polyene antibiotic antifungals, including amphotericin B and nystatin; azole antifungals, including clotrimazole, miconazole, ketoconazole, fluconazole, and itraconazole; and the cost of therapy. Throughout the article, the authors discuss the impact of these fungal infections on individuals with immunosuppressive diseases. 4 tables. 56 references. (AA-M).

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Vulvodynia and Vulvar Vestibulitis: Challenges in Diagnosis and Management Source: American Family Physician. 59(6): 1547-1556. March 15, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article reviews the diagnosis and management of vulvodynia, a problem most family physicians can expect to encounter. It is a syndrome of unexplained vulvar pain, frequently accompanied by physical disabilities, limitation of daily activities, sexual dysfunction, and psychologic distress. The patient's vulvar pain usually has an acute onset and, in most cases, becomes a chronic problem lasting months to years. The pain is often described as burning or stinging, or a feeling of rawness or irritation. Vulvodynia may have multiple causes, with several subsets, including cyclic vulvovaginitis, vulvar vestibulitis syndrome, essential (dysesthetic) vulvodynia, and vulvar dermatoses. Evaluation should include a thorough history and physical examination as well as cultures for bacteria and fungus, KOH microscopic examination, and biopsy of any suspicious areas. Proper treatment mandates that the correct type of vulvodynia be identified. Depending on the specific diagnosis, treatment may include fluconazole, calcium citrate, tricyclic antidepressants, topical corticosteroids, physical therapy with biofeedback, surgery, or laser therapy. Since vulvodynia is often a chronic condition, regular medical followup and referral to a support group are helpful for most patients. 8 figures. 1 table. 29 references. (AA).

Federally Funded Research on Fluconazole The U.S. Government supports a variety of research studies relating to fluconazole. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to fluconazole. 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 fluconazole. The following is typical of the type of information found when searching the CRISP database for fluconazole: •

Project Title: ACTG 323 FLUCONAZOLE AS THERAPY FOR OROPHARYNGEAL CANDIDIASIS Principal Investigator & Institution: Schooley, Robert T.; Professor of Medicine & Head; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002

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

Studies

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Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACTG 323/MSG40--USE OF FLUCONAZOLE AS CHRONIC SUPR THERAPY VS EPISODIC THERAPY Principal Investigator & Institution: Reichman, Richard C.; Professor; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACTG 323--FLUCONAZOLE AS CHRONIC SUPP. THERAPY VS. EPISODIC THERAPY IN HIV+ PTS Principal Investigator & Institution: Sacks, Henry S.; Director; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACTG 323--FLUCONAZOLE AS CHRONIC SUPPRESSIVE THERAPY VS EPISODIC THERAPY Principal Investigator & Institution: Macgregor, Rob R.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACTG 323--PHASE IV OPEN LABEL COMPARING CHRONIC SUPPRESSIVE THERAPY Principal Investigator & Institution: Bartlett, John G.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Compare the use of fluconazole as continuous prophylaxis versus episodic therapy in subjects with recurrent oral thrush. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALBICANS

AIDS:

COMBATTING

DRUG

RESISTANCE

OF CANDIDA

Principal Investigator & Institution: Cannon, Richard D.; University of Otago Leith St Dunedin, Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2004 Summary: (provided by applicant): Candida albicans is a pathogenic yeast that causes serious fungal infections in the immunocompromised and opponunistic Candida infections can be the first indication of immunosuppression in HIV+ individuals. AIDS patients frequently suffer from oropharyngeal candidiasis (OPC) and require antifungal

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therapy. In the 1990s there was a dramatic increase in the failure of fluconazole therapy for AIDS patients with OPC due to C. albicans strains developing fluconazole resistance. The most common mechanism responsible for high level fluconazole resistance in these yeast was over-expression of drug efflux pump Cdrl p. Globally, OFC remains a major opponunistic infection in HIVIAIDS, and the widespread use of fluconazole in the third world is likely to maintain pressure on C. albicans to develop resistance. The overall objective of this research is to use a novel strategy to improve the treatment of AIDS patients with oral candidiasis by combating azoleresistance in C. albicans. Specific objectives are to: 1. Employ a novel heterologous functional hyperexpression system to determine the mechanism of pumping by Cdrl p, using both in vitro mutagenized Cdrl p and Cdrl proteins from clinical C. albicans isolates (obtained from AIDS patients) that demonstrate high and low pump activities. 2. Use the heterologous functional hyper-expression of Cdrlp to screen a unique combinatorial Doctapeptide library for peptides that inhibit the pump. This work will validate a novel approach to combating azole-resistance in C. albicana An understanding of drug pumping mechanisms may indicate new ways to circumvent efflux-mediated resistance. This project is expected to identify a lead compound with the potential to sensitize resistant strains to azole antifungals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AMBISOME VS APHOTERICIN B IN AIDS PATIENTS WITH CRYPTOCOCCAL MENINGITIS Principal Investigator & Institution: Javaly, Kedernath; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANALYSIS OF THE CANDIDA ALBICANS PROTEOME Principal Investigator & Institution: Lopez-Ribot, Jose L.; Associate Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Candida albicans is by far the most frequently isolated human mycotic agent. In the oral cavity, oropharyngeal candidiasis (OPC) is a significant cause of morbidity in patients with HIV or AIDS. Other forms of mucosal candidiasis are also frequent in different patient populations such as infants, denture wearers, the elderly, and following antibiotic therapy. Azole derivatives, in particular fluconazole, are generally effective in the treatment of mucosal candidiasis. However, resistance has emerged as an important clinical problem. Large-scale DNA sequencing has provided an important sequence infrastructure for protein analysis. The term "Proteomics" refers to large-scale characterization of the proteins present in a cell, tissue or organism (the proteome) and involves the combined application of techniques to resolve, identify, quantitate and characterize proteins, as well as bioinformatics tools to store, communicate and interlink the resulting information. The experimental design of this proposal takes advantage of the recently completed NIDCR-funded Candida albicans genome sequencing project. The post-genomic era offers unprecedented opportunities to study host-fungal interactions. The specific aims of this proposal include: i) a pilot feasibility study of the analysis of the C. albicans proteome under a wide variety of conditions and development of a searchable proteomic map and

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11

database as a resource for the fungal community, ii) analysis of C. albicans azole resistance by proteomics and identification of proteins implicated in the regulatory networks of multidrug resistance. We will expect that these projects will establish the foundations for creating a fundamental tool for the C. albicans research community and for providing a detailed large-scale study of a biological phenomenon (drug resistance) with important clinical repercussions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADJUVANTS

ANTIFUNGALS

FROM

MARINE

INVERTEBRATES--AIDS

Principal Investigator & Institution: Molinski, Tadeusz F.; Professor; Chemistry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 01-MAR-1997; Project End 31-MAY-2005 Summary: (provided by applicant): AIDS-related fungal infections are important targets for reduction of mortality and improvement in the quality of life for people living with AIDS. Each new generation of azole drugs, such as fluconazole, have succumbed to recurrent cross resistance. Natural products are represented among clinically useful antifungal agents. Marine invertebrates, particularly Porifera (sponges) that produce chemically diverse libraries of natural products, some of which show antifungal activity. The general goal of this competitive renewal is to find and identify small molecules from marine organisms that are active against fluconazole-resistant strains of Candida albicans and inherently fluconazole-resistant non-albicans species, including Candida glabrata and Candida krusei and use these as prototypes leads for antifungal drugs. We plan to prepare and screen extracts for antifungal agents using mechanism-selective approach that may be useful identifying new leads for antifungal therapy. This program embodies a rational search for compounds with unique mechanisms of action, including inhibition of fungal sphingolipid biosynthesis, that complement current therapies and intervene at strategic points in fungal cell metabolism or life cycle. Active components will be isolated by a combination of solvent-partitioning, chromatography, liquid-liquid centrifugal counter current chromatography and other techniques. The in vitro antibiotic susceptibilities of pathogenic fungi will be evaluated in a panel of fluconazole-resistant fungi. Selected leads will be advanced to in vivo evaluation in murine models of C. albicans, Cryptococcus neoformans and C. glabrata. The structures of novel compounds will be determined by a combination of spectroscopic techniques including mass spectrometry, nuclear magnetic spectroscopy, circular dichroism and X-ray crystallography. Absolute stereochemistry of chiral molecules will be determined using a combination of chiroptical techniques and chemical degradation. Derivatives of existing leads, including the C. glabrata-specific dimeric sphingolipid, oceanapiside, will be synthesized de novo or by semi-synthetic modification to prepare limited libraries of analogs for structure-activity studies. Optimized leads identified from those libraries will be advanced to in vitro and in vivo evaluation. The strengths of this program include a successful track record in targeting emergent pathogenic fungi, including fIuconazole-resistant Candida species that are of importance in human health, and maximization of chemical diversity to enhance the chances of discovery of natural product antifungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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•

Project Title: REGULATION

AZOLES

AND

CANDIDA

IN

AIDS-TRANSCRIPTIONAL

Principal Investigator & Institution: White, Theodore C.; Associate Member; Seattle Biomedical Research Institute 307 Westlake Ave N, Suite 500 Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 30-SEP-1994; Project End 30-APR-2008 Summary: (provided by applicant): Candida albicans, a pathogenic yeast, is the cause of fungal infections in immune-compromised patient populations including AIDS patients. These infections are treated with antifungal drugs including the azole fluconazole. Extensive azole use has resulted in resistance which is a growing and significant problem. As molecular mechanisms of resistance are identified, it becomes important to understand the pathways which regulate these mechanisms in both susceptible and resistant strains. Currently, little is known about the transcriptional regulation of the ERG11 gene in C. albicans, the product of which is the target of the azole drugs and a biosynthetic step in the synthesis of ergosterol, the fungal equivalent of cholesterol. The Overall Goal of this research is to understand the interactions between azoles and C. albicans by studying the expression and regulation of genes associated with resistance. This proposal focuses on the transcriptional regulation of ERG11. The Specific Aims are: 1) To characterize regions of the ERG11 promoter that are important for transcriptional regulation. 2) To identify and characterize the transcription factors that regulate the ERG11 promoter. 3) To characterize the newly described ECM22 transcription factor in C. albicans for its effect on ERG11 and azole susceptibility; disruption of gene results in azole hyper-susceptibility. 4) To characterize additional C. albicans genes, identified by genomic approaches, that regulate azole susceptibility. The interactions between azoles and fungal cells, and the resulting azole drug resistance, will continue to be a clinically significant issue for the foreseeable future. Understanding the transcriptional regulation of ERG11 and of ergosterol biosynthesis, and understanding how fungal cells respond to azole drugs may lead to improvements in diagnosis, treatment and prevention of fungal infections and of resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGY AND DRUG RESISTANCE OF CANDIDA BIOFILMS Principal Investigator & Institution: Ghannoum, Mahmoud A.; Professor and Center Director; Dermatology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2005 Summary: (provided by the applicant): Candida-associated denture stomatitis (chronic atrophic candidiasis) is the most prevalent superficial oral infection and the most common form of Candida-associated disease. The etiology of denture stomatitis involves dental plaque. Dental plaque consists of a complex biofilm of bacteria and yeasts, predominantly Candida albicans. C. albicans biofilms have received much less attention than bacterial biofilms, and our present knowledge of their biology and drug resistance is at a rudimentary stage. Frequent denture stomatitis treatment failures combined with a steadily increasing population of elderly people, many of whom will be endentulous, make this area of study particularly important. The long-range goal of our work is to understand the biology and drug resistance of C. albicans biofilms. Our preliminary work in this new area resulted in the successful development of a reproducible model of C. albicans-associated biofilms (Publication #1). Since the last submission, we used this model to: 1) define the three stages of C. albicans associated biofilm development, 2) demonstrate that C. albicans biofilm is a highly heterogeneous

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13

structure, 3) show that the antifungal resistance of C. albicans biofilm increases in conjunction with biofilm development, 4) show that C. albicans has greater ability than the less pathogenic C. parapsilosis and Saccharomyces cerevisiae to form denture biofilm, and 5) show that C. albicans genes are differentially expressed under biofilm and planktonic conditions. Additionally, we initiated efforts to construct a C. albicans DNA array, and developed a bioprosthetic associated candidal biofilm model. Importantly, our studies showed that biofilm grown in our in vitro model has similar morphology as that growing in vivo on a catheter obtained from a patient with catheterassociated infection. Specific aims of the current proposal are: Specific Aim 1: Use our established biofilm model to determine the antifungal susceptibility profiles of C. albicans isolates obtained from denture stomatitis patients, and to study the effect of antifungal agents on the growth kinetics of C. albicans bioflims. Specific Aim 2: Investigate the mechanism(s) responsible for increased antifungal resistance of biofilmassociated C. albicans. Specific Aim 3: Identify genes that are involved in the formation and contribute to the development of antifungal resistance of C. albicans biofilms. By studying biofilm model systems and applying this knowledge to the patient population, we will gain a wealth of data about the biology and drug resistance of C. albicans in biofilms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: C. ALBICANS FROM HIV+ INDIVIDUALS&ITS ROLE IN DRUG RESIS Principal Investigator & Institution: Vargas, Kaaren G.; Dows Inst for Dental Research; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant) As a recent graduate from a PhD program and newly appointed assistant professor at The University of Iowa, I feel that I would benefit significantly from the Faculty Transition portion of the K22. In conjunction with the completion of the research proposed, the PI will receive training in the ethics of biomedical research. The research project itself will receive guidance from a number of very experienced researchers. Drs. Michael Pfaller, Christopher Squier, Georgia Johnson, Philip Wertz and David Soll. The research experience that is outlined in this proposal will enable me to develop into an independent investigator and contributor to the advancement of science. I will receive extensive support from my advisors and the College of Dentistry. Research facilities are available for my use and courses are offered that will enable me to conduct research in a responsible manner. The. experimental portion sets out to answer the following questions: 1. What is the antifungal susceptibility of C. albicans switch phenotypes isolated from HIV-positive individuals? 2. Are there differences in uptake of antifungals among different switch phenotypes or differences in ergosterol content in the presence of antifungals and are there differences in expression of known multi-drug resistance genes (MDR1, CDR1 and ERG11) among the different switch phenotypes? and 3. Are different switch phenotypes better able to survive under in vivo conditions of antifungal drug therapy for candidiasis? For this, a collection of samples from HIV+ and HIV- individuals previously collected by the PI and Dr. Michael Pfaller will be used. From these studies we hope to increase our understanding of the role that phenotypic switching plays in antifungal drug resistance, which is an increasing problem in severely immunosuppressed individuals. This increased knowledge could lead to improvements in treatment of oral candidiasis in all immunocompromised individuals. In the long-term, I would like to make significant

14

Fluconazole

contributions to science in the area of antifungal drug resistance. It is an exciting area of research and I feel strongly that I have the motivation to accomplish this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CS96 209 SCH56592 VERSUS FLUCONAZOLE IN THE TREATMENT OF OROPHARYNGEAL CANDIDA Principal Investigator & Institution: Wheat, Joseph; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENINGITIS

DISCONTINUATION

ANTIFUNGAL

FOR

CRYPTOCOCCAL

Principal Investigator & Institution: Aberg, Judith; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF FLUCONAZOLE ON PHARMACOKINETICS OF TACROLIMUS Principal Investigator & Institution: Benet, Leslie; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FLUCONAZOLE IN OROPHARYNGEA CANDIDIASIS

HIV+

SUBJECTS

WITH

RECURRENT

Principal Investigator & Institution: Valentine, Fred; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANDIDIASIS

FLUCONAZOLE

RESISTANCE

IN

OROPHARYNGEAL

Principal Investigator & Institution: Patterson, Thomas; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002 Summary: This protocol is designed to study the development of fluconazole resistance in patients with advanced immunodeficiency, to correlate that resistance with clinical response and to test the effectiveness of using high doses of fluconazole to treat

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15

oropharyngeal infections. The study is presently in its 2-year clinical follow-up phase and is closed to new enrollment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FLUCONAZOLE VS EPISODIC IN HIV+ PTS WITH CANDIDIASIS Principal Investigator & Institution: Flexner, Charles W.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Compare the use of fluconazole as continuous prophylaxis versus episodic therapy in subjects with recurrent oral thrush. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FOCUSED PARALLEL SYNTHESIS OF DICATION ANTIFUNGAL AGENTS Principal Investigator & Institution: Tidwell, Richard R.; Professor of Pathology and Laboratory Me; Pathology and Lab Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: The proposed studies stem from our previous research on the antifungal activity of dicationic molecules. These initial in vitro studies on over 300 dication molecules showed that leading compounds were both inhibitory and fungicidal against Candida albicans and Cryptococcus neoformans with MIC80S of <0.09 g/mg and MFCs of 0.10 g/ml against both organisms. Our studies also demonstrated that the compounds were active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans and fluconazole-resistant strains of C. albicans and C. neoformans. An outside laboratory confirmed our in vitro data and also showed that leading compounds against A. fumigatus had IC50 values that were less than 0.0050 mu g/ml and selectivity indices, when compared to HeLa cell, over 2000. More importantly, the outside laboratory demonstrated that one of the compounds was equally as active as fluconazole in a mouse survival model of candidiasis. The above findings along with our studies on the toxicology and pharmacology of dicationic compounds clearly show that these molecules have great potential as antifungal agents. The current proposal will expand these initial studies by synthesizing over 2,400 related molecules per year utilizing combinatorial chemistry technology and testing these molecules in an in vitro model for activity against C. albicans and A. fumigatus and toxcity in THP-1 cell (human monocytes). Since the exact mechanism of antifungal activity is not known, and previous results indicated that more than one mode of action may contribute to their antifungal activity the compounds will be screened against the organism rather than a specific target. The antifungal data will be subjected to detailed QSAR and modeling studies and these results will be used to guide either the expansion of proposed libraries, the development of new libraries, or off resin synthesis of a small subset of related molecules. Finally, selected molecules will be tested in animal models of fungal infections. This proposal brings together a seasoned group of investigators with over seven years of successful collaboration on antimicrobial research. Utilizing the combinatorial chemistry methodology to build focused libraries coupled with highthroughput screening and data management will optimize the groups chances of achieving the goal of this project; the discovery of new antifungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

16

•

Fluconazole

Project Title: GENETIC CONTROL OF NUTRITION STARVATION IN YEAST Principal Investigator & Institution: Fink, Gerald R.; Professor of Molecular Genetics, Mit; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2004; Project Start 01-JUL-1984; Project End 30-NOV-2007 Summary: This proposal will use the molecular genetics of Saccharomyces cerevisiae and Candida albicans to determine the role of polyploidy and gene duplications in gene expression. Genomes have evolved by duplication of existing genetic material, either whole genomes or individual genes; however, such duplications can lead to abnormal growth. Many tumors contain a large proportion of cells that are hyperploid, and, for some, increased ploidy carries a good prognosis, predicting an increased sensitivity to anti-mitotic drugs. Experiments are designed to identify all the Saccharomyces genes required for polyploid formation and for the survival of polyploid cells in stationary phase using whole genome knockout libraries. The role of gene silencing in the control of gone expression in polyploids will be determined by whole genome chromatin immunoprecipitation. The mechanism of gene silencing and variegation will be elucidated for the FLO genes, a highly duplicated gone family with one expressed locus (FL011), and many silent subtelomeric members. These experiments will determine the role of chromatin factors, nutrition, mutation, and recombination in silencing and desilencing the ensemble of FLO genes. Experiments are also designed to reveal the mechanism by which the non-telomeric gene FL011 switches epigenetically between the "on" and "off" states. A genome wide screen will identify the prevalence of variegation in gene expression. As FLO genes are the cell surface adhesins of fungi, their ability to switch could be critical virulence factors in pathogens. The importance of silencing and desilencing for human health will be determined in the human fungal pathogen, Candida albicans, an obligate diploid. Candida's resistance to the antifungal agent, fluconazole, is unstable in strains heterozygous for the recessive erg3 mutation. We will determine the role of diploidy and the histone deactylases in generating high-level drug resistance and will screen the Candida genome for other genes that lead to fluconazole resistance by this silencing mechanism. These Candida studies could identify the factors that will improve the effectiveness of current antifungal therapies. Experiments using DNA microarrays are designed to identify compounds used by Saccharomyces to sense its density. The experiments proposed will lead to a deeper understanding of the ability to proliferate at low cell densities, a more realistic scenario for fungal pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC VARIABILITY OF THE YEAST CANDIDA ALBICANS Principal Investigator & Institution: Sherman, Fred; Professor; Biochemistry and Biophysics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-MAR-1993; Project End 30-NOV-2004 Summary: (Verbatim from Applicant's Abstract): Clinical isolates of the pathogenic yeast Candida albicans exhibit extensive variation in electrophoretic karyotypes and in phenotypic polymorphism. In this connection, systematic studies conducted in our laboratory revealed that laboratory strains of C. albicans spontaneously give rise to high frequencies of many different types of mutants having altered phenotypes and karyotypes. The significance of the chromosomal alterations was established with spontaneous mutants that acquired the ability to utilize alternative carbon sources. A causal relationship was established with a series of Sou- to Sou+ to Sou- to Sou+ derivatives, in which the Sou- (L-sorbose none-utilizing) and Sou+ (L-sorbose utilizing) strains were, respectively, disomic and monosomic for chromosome 5. Furthermore,

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17

transcription of the SOU1 gene, required for L-sorbose utilization, was regulated by the copy number of chromosome 5, in spite of the fact that SOU1 resides on a different chromosome. A hypothetical negative regulator, CSU51, was postulated to reside on chromosome 5, such that transcription of SOU1 is dependent on the ratio of the CSU51 to SOU1 copy number. Other examples of negative regulation by chromosome copy number include the utilization of D-arabinose, Aru- to Aru+, and resistance to the antifungal agent, fluconazole, FluS to FluR, thus establishing a general regulatory mechanism. The major long-term goal of the proposed research is to determine mechanisms of this newly-discovered regulatory process in C. albicans, by which gene expression is controlled by chromosome copy number. Several candidates of the negative regulator residing on chromosome 5 have been isolated from a library of chromosome 5 DNA, and these are being characterized. These regulators will be investigated for their direct or indirect interaction with the SOU1 structural gene. The additional negative regulators, which were retrieved from a total genomic library, and which are located on different chromosomes, will be analyzed for their involvement in the regulatory network controlled by chromosome copy number. This work establishes for the first time a negative regulatory network for a secondary carbon source in an important pathogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGEN

GENOMIC

REARRANGEMENTS

AND

REGULATION

OF

Principal Investigator & Institution: Magee, Paul T.; Professor; Genetics, Cell Biology & Develpmnt; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFICATION OF C ALBICANS FLUCONAZOLE RESISTANCE GENE Principal Investigator & Institution: Mitchell, Aaron P.; Professor; Microbiology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): C. albicans is the most common fungal pathogen of humans. It causes an array of infections, ranging from oral and vaginal candidiasis to life-threatening candidemia and invasive disease. Fluconazole and other azoles are the major antifungals currently in use, in particular for long-term treatment. This application focuses on the mechanisms by which fluconazole resistance arises in C. albicans. Three major mechanisms that contribute to azole resistance: overexpression of drug efflux pumps (CDR1, CDR2, and MDR1 gene products), overexpression of the fluconazole target gene ERG11, and mutational alteration of ERG11. Our understanding of resistance mechanisms is limited in two ways, however. First, the mutations that cause overexpression of efflux pumps or of ERG11 have not been associated with genetic loci, so the genetic basis for resistance is unknown. Second, many azole-resistant clinical isolates do not overexpress CDR1, CDR2, MDR1, or ERG11, and do not have alterations of the ERG11 gene. Thus, these isolates have become resistant through an uncharacterized mechanism. We will use the C. albicans genomic sequence for functional identification of transcriptional regulators that govern fluconazole resistance

18

Fluconazole

with two strategies. First, we will new fluconazole resistance regulators through insertional mutagenesis targeted to transcription factor genes. Second, we will circumvent problems associated with redundant regulatory proteins through the strategy of "transcription factor reprogramming." The strategy uses transcription factor fusion proteins that have hyperactive and dominant negative characteristics. These approaches will define the regulators that govern known resistance mechanisms and may reveal the regulators that govern other clinically relevant resistance mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFECTIOUS COMPLICATIONS Principal Investigator & Institution: Corey, Lawrence; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 18-MAR-2002; Project End 30-NOV-2006 Summary: (provided by applicant): The spectrum of infectious complications after hematopoietic stem cell transplantation (HSCT) has been markedly altered in the last decade. Early ganciclovir therapy has reduced CMV infection but its hematopoietic toxicity limits its use, and the lack of immune reconstitution to CMV, especially among those with GVHD, has resulted in a high incidence of CMV reactivation disease late after transplant. Also, while fluconazole prophylaxis has markedly reduced invasive candidal infections, the incidence of aspergillosis has tripled. Most cases now occur in the nonneutropenic, but highly immunosuppressed host, illustrating the potential importance of T cell immunity in this entity. Subclinical primary CMV infection (i.e., acquisition of CMV infection below the threshold of current antigenemia assays) in CMV seronegative recipients of a seropositive donors (D+R-) appears to be a newly identified risk factor for the acquisition of pulmonary aspergillosis and invasive bacterial infections. The specific aims of the project are: Specific Aim 1. To reduce the morbidity and mortality of late onset CMV disease after HSCT. A randomized doubleblind study will be performed to examine whether valganciclovir will prevent late onset CMV disease without increased CMV resistance or further delay in CMV immune reconstitution. Specific Aim 2. To determine the role of T cell mediated immunity in the development and outcome of post-engraftment aspergillosis. CD4+ and CD8+ T cell responses to A. fumigatus antigens and neutrophil anti-hyphal activity will be assessed longitudinally in allogeneic HSCT recipients to define whether those with altered responses are at greater risk of infection and poor outcome. Studies to define responses to purified antigen preparations will be initiated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: KARYOTYPES OF C. ALBICANS FLUCONAZOLE RESISTANT MUTANTS Principal Investigator & Institution: Rustchenko, Elena; Biochemistry and Biophysics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Through the work of many groups, fluconazole resistance in some, but not all clinical isolates has been associated with the gene target of the drug, ERG11, as well as genes for cellular pumps, CDR1, CDR2 and MDR1. The mechanisms implicating these genes in resistance are not fully understood, and it is uncertain that the entire repertoire of fluconazole genes have been identified. In our recent work, we showed for the first time that under laboratory condition 10 independent fluconazole resistant mutants that derived after a short exposure of one

Studies

19

week to the drug, all lost a copy of chromosome 4. The mRNA level of the above mentioned genes in these mutants was not changed. A total of 7 independent fluconazole resistant mutants that derived after at least one month of exposure to the drug, all possessed the diminution of chromosome 4, and acquired a second specific change, an extra-copy of chromosome 3. Consistently, the expression of the gene CDR1, which is carried on the duplicated chromosome, but not of the other genes, was increased. Our results are remarkably similar to the published data describing series of C. albicans sequentially isolated clinical strains with a progressive increase of resistance over time, which did not initially show or did not have any mutations or overexpression of the genes associated with the resistance. We propose to test our hypothesis that the primary response of clinical isolates to fluconazole is specific changes in chromosomal copy number. The higher resistance levels of later clinical isolates can be viewed as secondary changes, which occur as a result of accumulation of gene mutations under prolonged selective pressure. We developed special procedure to isolate and handle C. albicans series of sequential genetically related strains from patients undergoing fluconazole treatment, thus protecting the isolates from stresses other than action of fluconazole, which can induce undesirable chromosomal instability. The reliable series of strains will be characterized for their electrophoretic karyotypes. If the change in copy number of a specific chromosome(s) is/are observed with clinical samples resistant to fluconazole, we are in the position to further study the still unknown genes responsible for this novel mechanism of resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF INHIBITORY DRUG INTERACTIONS Principal Investigator & Institution: Kunze, Kent L.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The long-term objective of the research described in this grant proposal is to better understand metabolism-based drug-drug interactions that are underpredicted from in vitro data. This is important because underprediction of effect has negative consequences for drug therapy and the development of new drugs. It is also important because these outliers represent a significant fraction of clinically relevant drug-drug interactions. An in-depth understanding of why predictions fail should improve predictive efforts. The interactions we propose to study are drawn from the larger class of interactions that appear to arise as the result concentrative cell uptake and/or metabolites of the interactant drug. Predictive quality is degraded because the magnitude of the inhibition depends not only on the concentration of the interactant drug at the active site, but also on the activity of the enzymes involved in converting the drug to the proximate inhibitory metabolite as well as the mechanism of metabolite inhibition. The first section of this proposal investigates two potent inhibitors of P450catalyzed drug metabolism, fluvoxamine and itraconazole, who's in vivo effects are 10to 100- fold higher than predicted. Fluvoxamine causes potent and differential inhibition of at least 4 important human P450' s in vivo. Aims 1-3 will identify the sources of the underprediction for each enzyme by examining the importance of concentrative uptake as well as direct inhibitory effects of fluvoxamine, itraconazole and their major metabolites on enzyme activities in microsomal preparations and human hepatocytes. The finding that time dependent, persistent inhibition of CYP3A4 activity by itraconazole is observed in microsomes and intestinal cells further suggests that itraconazole is a mechanism-based inhibitor of this important enzyme. Aim 4 will assess if other factors, such as concentrative uptake, are required to fully explain the effect of

20

Fluconazole

itraconazole and, if so, to identify them. The second section of the proposal addresses the propensity of alkylamine containing drugs to elicit irreversible inhibition of enzyme activity via formation of MI complexes in vivo and in vitro. This process requires that the alkylamine undergo as many as 4 rounds of oxidation to the corresponding Cnitroso metabolite prior to the inhibitory event. This very complex type of inhibition has not been fully characterized and a deeper understanding of the underlying mechanisms is critical for meaningful and reproducible in vitro-in vivo predictions of inhibitory effect. Aims 5 and 6 of this proposal set out to fully describe the kinetics of the system and evaluate the limits and advantages of a less complex empirical approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC INTESTINAL DRUG INTERACTIONS Principal Investigator & Institution: Thummel, Kenneth E.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term goal of the research described in this grant proposal is to understand the mechanistic basis for inhibitory drug interactions involving human CYP3A4. This is important for the avoidance of adverse events with the numerous drugs in clinical use today that are either a substrate or inhibitor of the enzyme. It will also aid greatly in predicting the in vivo inhibitory potential for new molecular entities under develop. We hypothesize that effects of several clinically important inhibitory drugs on the first-pass clearance of CYP3A substrate occurs predominantly with the intestinal mucosa, and they can last well beyond the period of inhibitor absorption. This will be investigated with the following Specific Aims: I. To determine whether the inhibitory effect of azole anti-fungals on the first-pass metabolism of the CYP3A marker midazolam occurs predominantly within the intestinal mucosa rather than liver, and whether this preferential inhibition persists will beyond the period of inhibitor absorption due to sequestration of inhibitor in the mucosa. II. To determine whether inhibition of intestinal rather than hepatic first-pass is the predominant mechanism by which dialkylamine inhibitors elevate the systemic availability of orally administered midazolam, and to determine whether the time-course of inhibition parallels the formation of a slowly reversible MI-CYP3A complex. III. To determine if the in vivo effect during multiple dosing of a prototype macrolide inhibitor, erythromycin, an oral midazolam bioavailability, depends on the amount of CYP3A4 expressed in the intestinal mucosa and the accumulation over time of the di-desmethyl erythromycin metabolite in that tissue. We will employ three experimental paradigms; pharmacokinetic studies in healthy human volunteers; in vitro metabolic studies in human-derived Caco-2 cell culture monolayers; and in vivo intestinal extraction studies in a domestic pig model. This three-tiered approach should allow us to identify the contribution of readily predictable, reversible interactions between inhibitor and substrate, and current unpredictable, slowly reversible phenomena such as intracellular inhibitor sequestration and MI complex formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MK 0991 VS FLUCONAZOLE IN ESOPHAGEAL CANDIDIASIS Principal Investigator & Institution: Graybill, John R.; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002

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Summary: This study will evaluate the safety, tolerability and efficacy of a new antifungal agent as compared to fluconazole in the treatment of esophageal candidiasis. Patients will be stratified by neutrophil count and randomized to either the study drug or fluconazole. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MK-0991 VS FLUCONAZOLE FOR ESOPHAGEAL CANDIDIASIS Principal Investigator & Institution: Pratha, Vijaya; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW DRUGS FOR OPPORTUNISTIC INFECTIONS Principal Investigator & Institution: Clark, Alice M.; Vice Chancellor for Research and Sponsor; Natl Ctr/Develop Natural Prod; University of Mississippi P.O. Box 907 University, Ms 386770907 Timing: Fiscal Year 2004; Project Start 01-JUL-1989; Project End 30-JUN-2009 Summary: (provided by applicant): The overall goal of this project is to identify new compounds, as well as new pathways to discover new compounds for development of new treatments for the major AIDS- and cancer-related disseminated fungal infections. This is a competitive renewal of R01 AI27094 and expands our current work in the area of antifungal drug discovery, with an emphasis on the identification of mechanistically characterized and validated novel antifungal compounds. Our approach is to validate the unique lead compounds with antifungal and resistance-reversing properties that were identified in the previous project period, determine their mechanisms of action, and evaluate their in vivo efficacies against resistant strains. The specific aims of this project are: 1. Validate new lead compounds (already in hand) that show reversal of fluconazole resistance by using efflux pump assays and genomic approaches; 2. Determine mechanisms of action of lead antifungal compounds using genomic profiling approaches, and validate the molecular targets identified using genetic and biochemical strategies; 3. Evaluate the in vivo efficacy of selected lead compounds in murine models of systemic mycoses, including activity against resistant strains; and, 4. Identify other new lead compounds that exhibit unique mechanistic profiles. Successful completion of the proposed work will yield new prototype lead compounds that will serve as templates for development of new classes of antifungal agents, as templates for the development of new drugs to be used in combination with existing antifungal agents to reverse resistance to these agents, and as probes to identify novel mechanisms of action that can be exploited in the future search for other new derivatives. This information will expand the foundation of knowledge regarding the therapeutic control of these infections and the understanding of the basic biology of these pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL ANTIFUNGAL DRUG TARGETS IN CRYPTOCOCCUS NEOFORMANS Principal Investigator & Institution: Heitman, Joseph B.; Professor; Molecular Genetics and Microbiology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006

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Summary: Fungal infections are increasingly common as a result of AIDS, transplantation, high dose chemotherapy, steroid treatment, antibiotic treatment, and invasive procedures. However, existing antifungal agents are limited to amphotericin B, flucytosine, and azoles, and drug resistant strains are emerging. We propose to elucidate signal transduction cascades regulating fungal growth and virulence as targets for antifungal drug development. We propose studies on both Candida albicans, the most common human fungal pathogen, and Cryptococcus neoformans, the leading cause of fungal meningitis and an important opportunistic fungal pathogen. We have discovered that the immunosuppressive drugs rapamycin, cyclosporin A, and FK506 have potent antifungal activity. In studies supported by this award, we have identified the fungal drug target proteins, including FKBP12, the Tor1 kinase, and two cyclophilin A homologs. Our studies demonstrate that the antifungal effects of rapamycin are mediated via a complex with FKBP12 that inhibits the fungal Tor1 kinase homolog. We have identified nonimmunosuppressive analogs of each of these drugs that retain antifungal activity. By genetic and biochemical approaches, we show that these analogs take advantage of structural differences between host and fungal enzymes, sparing immune function while impairing fungal cell growth. Finally, we have identified examples of potent synergistic drug interactions. For example, the calcineurin inhibitors cyclosporin A and FK506 are potently synergistic with azoles in Candida albicans. Here we propose to establish the cellular functions and targets of the rapamycin target protein Tor1. The TOR1 gene will be disrupted in diploid strains of C. neoformans to test if it is essential. Targets of the Tor kinase will be identified by genetic and two hybrid screens, and by analyzing gene expression with genome arrays. We will also identify the targets of the C. neoformans cyclosporin A target proteins, the Cpa1 and Cpa2 cyclophilins, which are important for cell growth and virulence. We will determine the molecular basis of synergistic drug interactions. First, we will identify a novel target of the FKBP12-FK506 complex that is synergistic with proton pump inhibitors in C. neoformans. Second, we will focus on the roles of FKBP12 and calcineurin in azole action in C. albicans, testing the hypothesis that calcineurin is either essential or becomes essential during cell membrane stress as a result of azole treatment. Finally, we will test rapamycin and nonimmunosuppressive rapamycin analogs, and the synergistic combination of calcineurin inhibitors and azoles, in animal models of cryptococcosis and candidiasis. Our long term goal is to identify unique targets and develop novel antifungal drug therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL AZOLE RESISTANCE MECHANISMS IN CANDIDA ALBICANS Principal Investigator & Institution: Rogers, P David.; Pharmacy; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2005 Summary: (provided by applicant): Azole antifungal resistance has emerged as a significant problem in the management of infections caused by a number of fungal species including Candida. This problem has had a significant impact in immunocompromised patient populations, particularly those suffering from AIDS. While the use of highly active antiretroviral therapy (HAART) has reduced the frequency of OPC among AIDS patients in the United States, limited access to such therapy in underdeveloped countries, poor compliance, and toxicity associated with HAART will likely contribute to an increase in this problem among AIDS patients world-wide. Understanding the molecular basis of azole resistance will facilitate the

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development of therapeutic strategies to circumvent this problem and improve the utility of the azole class of antifungal agents. The aim of this proposal is to identify and characterize novel molecular mechanisms of azole antifungal resistance in Candida albicans. The central hypothesis behind this proposal is that specific molecular mechanisms are responsible for the stepwise acquisition of azole antifungal resistance in C. albicans. We will use an integrated functional genomic and proteomic approach to characterize and compare the gene expression and proteomic profiles of serial isolates within and between multiple matched sets of azole-susceptible and -resistant isolates of C. albicans. These studies will identify genes and gene products that are associated with the azole resistance phenotype. They will also identify genes and gene products that are coordinately regulated with known resistance mechanisms and hence lend insight into the regulation of these mechanisms. We will also screen azole resistant isolates for genes required for this phenotype using an antisense cDNA library. Targeted gene disruption and over-expression will be used to assess the role of candidate resistance genes in this process. These mutants will then be examined for changes in in vitro azole susceptibility, and in certain cases for secondary effects on the azole resistance gene expression and proteomic profile. Additional studies will examine the nucleotide sequences of key genes for point mutations that may play a role in this process. These studies will further elucidate the molecular basis for azole antifungal resistance and will identify novel targets for future work towards the development of compounds that will both abrogate resistance and enhance the utility of the azole class of antifungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PFIZER R 0437:STUDY OF FLUCONAZOLE + AMPHOTERICIN B IN TREATMENT OF C Principal Investigator & Institution: Hyslop, Newton E.; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACODYNAMICS IN ANTIFUNGAL RESISTANCE Principal Investigator & Institution: Andes, David R.; Assistant Professor; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): The research performed in the context of the K08 follows work as a fellow and by combining pharmocodynamics (PD) and molecular biology will open the development of an entirely untapped field of study. C. albicans is the most common opportunistic pathogen in HIV infected patients. Azoles are frontline agents for treatment of Candida infections, however therapy remains suboptimal and several mechanisms of azole resistance have recently emerged. There is a need for improved therapy and an understanding of drug exposure factors that lead to and prevent of the emergence of resistance. The proposed research is divided into two phases. (l) In phase one, azole PDs will be studied in a murine model. The findings obtained in the PD studies will be used to optimize dosing of azoles and investigate the relationship between the emergence of specific resistance mechanisms and azole dosing using (a) reconstruction experiments with a susceptible parent strain, doped with a fixed level of the genetically related resistant mutant strain and (b) a strain which has demonstrated temporary phenotypic resistance. (2) In phase two, basic studies of gene

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expression in C. albicans will be undertaken and correlated with results of phase I PD studies. Serial analysis of gene expression (SAGE) will be used to study mRNA abundance in C. albicans on a genome-wide basis. The biologic variables will include: the adaptive response of C. albicans to azole antibiotics (a) during the initial exposure, (b) following exposure during period of inhibition and regrowth, or the postantifungal effect (PAFE), and (c) the effect of specific known resistance mutations on these responses. The candidate's goal is to integrate knowledge of antifungal PD and the acquisition of approaches and skills in molecular biology through the completion of this grant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHASE IV RANDOMIZED STUDY OF FLUCONAZOLE AS CHRONIC SUPPRESSIVE THERAPY Principal Investigator & Institution: Goldman, Mitchell; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POTENTIATORS OF FLUCONAZOLE ACTIVITY IN CANDIDA Principal Investigator & Institution: Markham, Penelope N.; Head, Research Biology; Influx, Inc. 2201 W Campbell Park Dr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-DEC-2003 Summary: (provided by applicant): The goal of this Phase II SBIR project is to develop a clinically useful potentiator of the most widely used antifungal drugs, azoles. The major shortcoming of azole drugs is that they do not kill fungi but merely inhibit their growth. In fact, for the most medically important fungal pathogen, Candida albicans, this growth inhibition is only partial. The survival of the pathogen in the presence of the drug is the likely cause of the recurrence of fungal infections and emergence of azole resistance. Our Phase I studies identified two compounds in whose presence azoles become strongly fungicidal. These compounds show no antifungal activity on their own and no toxicity to human cells in culture. Structural derivatives of these two leads, displaying improved activity and pharmacological properties, will be obtained through intensive synthetic efforts. The biological activity of these derivatives will be thoroughly characterized in vitro. Their ability to improve antifungal activity of fluconazole will be tested in a murine model of systemic candidiasis. Finally, the molecular mechanism of action of the potentiators will be investigated in biochemical and genetic experiments. It is expected that the compounds developed in this project will significantly improve the improve the effectiveness of antifungal therapy. PROPOSED COMMERCIAL APPLICATION: The commercial product envisioned is a fungicidal combination of fluconazole with an adjuvant that potentiates antifungal activity. Such a product would have a major impact on the therapeutic and prophylactic treatment options for systemic Candida infections Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION OF CANDIDIASIS IN CRITICALLY III PATIENTS Principal Investigator & Institution: Sylvester, Shelley L.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218

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Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The Candidate, Dr. Sylvester, is a post-doctoral fellow in Infectious Diseases and a doctoral candidate in the Graduate Training Program in Clinical Investigation at Johns Hopkins University. Through this award she seeks to become an independent investigator in patient-oriented research, with expertise in the area of Candida and candidiasis in compromised patient populations. Experts in clinical investigation, critical care, medical mycology, and biostatistics will mentor her. She will supplement her research activities and her knowledge of introductory biostatistics and epidemiology with advanced courses in clinical investigation, biostatistics and research ethics at the Bloomberg School of Public Health. To prepare for translational aspects of her future research, she will take courses in immunology, microbiology and molecular biology. Background - Candida is a deadly and increasingly common pathogen in critically ill patients. In certain patient populations, including critically ill surgical patients at Johns Hopkins, antifungal prophylaxis has been shown to prevent Candida infections. Antifungal prophylaxis has not been well studied in critically ill medical patients. The emergence of antimicrobial resistance among Candida species presents a major concern with regard to the widespread use of prophylaxis. Dr. Sylvester proposes to explore the ecology of Candida and the impact of antifungal prophylaxis in critically ill patients. Specific Aims. 1 ). To determine Candida species distribution and fluconazole susceptibilities in high-risk SICU patients and compare current species distribution and susceptibility data to data collected during a 1998-1999 randomized, double blind placebo-controlled trial of fluconazole prophylaxis in critically ill surgical patients at Johns Hopkins. 2). To determine Candida species distribution and fluconazole susceptibilities in high-risk MICU patients, to whom fluconazole prophylaxis is not given, and compare these data to data collected concurrently from high-risk SICU patients, to whom antifungal prophylaxis is routinely administered. 3). To evaluate, in a randomized, double blind, placebo-controlled trial, the effect of antifungal prophylaxis on the prevention of invasive Candida infection in high-risk, critically ill medical patients. Significance. The overall goals of this research are to define the ecology of Candida in critically ill patients, to define the impact of antifungal prophylaxis on this ecology, to assess differences in ecology and predictors of invasive infection in critically ill medical and surgical patients, and to develop a safe, effective strategy to prevent these often-fatal infections in critically ill medical patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED STUDY OF USE OF FLUCONAZOLE AS CHRONIC SUPPRESSIVE THERAPY Principal Investigator & Institution: Kelly, Meera; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF DRUG RESISTANCE GENES IN C. ALBICANS Principal Investigator & Institution: Kumamoto, Carol A.; Associate Professor; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This research project investigates the regulation of drug resistance genes in Candida albicans. Greater than 90% of AIDS patients suffer

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from oropharyngeal candidiasis (OPC). Fluconazole is the most commonly prescribed antifungal drug for these infections due to its efficacy and lack of side effects. Treatment failures with fluconazole have risen, most notably in AIDS patients with recurrent OPC that receive extended fluconazole therapy. The majority of treatment failures are due to fluconazole resistant C. albicans isolates. Although resistant C. albicans strain most often exhibit increased drug efflux due to the increased transcription of multidrug resistance pumps, little is known concerning the molecular mechanisms that lead to this increased transcription. C. aibicans drug resistant mutants have been isolated that increase transcription of the multidrug efflux pumps MDR1 and CDR2. These mutations fall into two classes: (i) transacting mutations that lead to high level expression of either MDR1 or CDR2, and (ii) cis-acting promoter mutations that lead to a more moderate, fluconazole-dependent increase in the transcription of either MDR1 or CDR2. The proposed research will analyze these mutations at the molecular level, determine the mechanisms that lead to increased transcription of these drug resistance pumps, and study the influence of drug selection regimens on the acquisition of these mutations. The long-term goal of these studies is to contribute to a more informed use of fluconazole with respect to prophylaxis, drug dosage regimens and the development of fluconazole resistant strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TDM & DRUG INTERACTIONS IN HIVINFECTED SUBSTANCE ABUSERS Principal Investigator & Institution: Morse, Gene D.; Chairman; Pharmacy Practice; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This application describes an innovative approach to the rapid assessment of complex drug interactions between protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs), and commonly prescribed medications including methadone, ethinyl estradiol, fluconazole, pravastatin, and fluoxetine in HIV-infected, substance abusers The proposed methodology employs a Therapeutic Drug Monitoring (TDM) program that will facilitate rapid determination of ART in subjects receiving multiple interacting medications Specific aims 1) Implement a TDM program that will establish a mechanism to investigate protease inhibitor (PI) and NNRTI pharmacokinetics in HIV-infected, substance abusers receiving ART, determine drug exposure parameters (Cmin, AUC) and inhibitory quotients (IQs), 2) Determine the pharmacokinetics of selected interacting medications (methadone, ethinyl estradiol, fluconazole, pravastatin, fluoxetine) in HIV-infected, substance abusers receiving ART, 3) Determine in vitro and ex vivo total and unbound plasma concentrations of protease inhibitors and NNRTIs in HIV-infected, substance abusers utilizing novel analytical approaches including HPLC, LC-MS-MS and capillary electrophoresis, 4) Develop and validate a capillary electrophoresis assay capable of enantiomeric separation to enhance the pharmacokinetic analysis of interacting medications, 5) Examine pharmacogenetic factors that may identify individuals at greater risk for insufficient or excessive systemic drug exposure while receiving complex regimens with multiple drug-drug interactions The proposed TDM-drug-drug interaction program integrates a comprehensive antiretroviral clinical pharmacology research group, an HPLC/LC-MS analytical facility, a pharmacometrics laboratory, a web-based TDM enrollment infrastructure, and four HIV clinical centers caring for substance abusers Innovative pharmacokinetic and pharmacodynamic modeling approaches to assess complex drug-drug interaction analyses of PI and NNRTIs from HIV-infected substance abusers and non-substance

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abusers will be conducted. Clinical sites will enroll subjects while drug measurement and data analysis will be conducted at the central pharmacology laboratory. These studies will provide insight into clinical interactions that face clinicians and patients today, and identify priority drug interactions that require more traditional pharmacokinetic trials to identify specific mechanisms of interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE YEAST ERGOSTEROL PATHWAY Principal Investigator & Institution: Bard, Martin; Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2004; Project Start 01-JUN-1995; Project End 31-MAY-2008 Summary: (provided by applicant): Serious fungal infections are rising due to the increased use of immunosuppressive agents (either employed to sustain organ transplants or as the result of cancer therapy). Membrane sterol and the sterol biosynthetic pathway have long been target sites for antifungal drugs. Two of the most widely used antifungal classes, the polyenes (amphotericin B) target plasma membranebound sterols and the azoles (fluconazole, and itraconazole) target the cytochrome P450mediated step, lanosterol C-14 demethylation. Saccharomyces cerevisiae contains the best characterized sterol pathway at the genetic and molecular levels and is an excellent model system to study the topographical organization of sterol enzymes and the interactions between these enzymes within one or more sterol complexes. The postsqualene pathway leading to ergosterol in fungi or cholesterol in animal cells share eleven enzymatic reactions in addition to a scaffold protein required for efficient C-4 demethylation. In the post-squalene pathway only two enzymes in the cholesterol pathway and three in the ergosterol pathway account for the structural differences between these molecules. One goal of this proposal is to co-immunoprecipitate the sterol biosynthetic enzymes in order to determine whether there is a single enzymatic complex or several interacting complexes leading to end-product sterol. Specific pair wise enzymatic interactions will be evaluated using a membrane two-hybrid system. In addition interactions between sterol biosynthetic enzymes and sterol esterification enzymes will also be studied. A second major goal of this proposal is to investigate how loss of the ERG27 gene product leads to loss of the upstream enzymatic reaction, the oxidosqualene cyclase (Erg7p). This interaction will be studied at the transcriptional and post-translational levels. A number of transcriptional activators and repressors that affect several genes in the sterol pathway will be studied. Among these are the UPC2 and ECM22, YER064c and MOT3. A screen for novel transcriptional regulators of the C4 demethylation genes will also be undertaken. Finally, we will complete our analysis of the ERG9 promoter which encodes the squalene synthase, the first enzyme in the mevalonate-sterol pathway dedicated to sterol synthesis. 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

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

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

Activities of fluconazole (UK 49,858) and ketoconazole against ketoconazolesusceptible and -resistant Candida albicans. by Hughes CE, Bennett RL, Tuna IC, Beggs WH.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172136

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Activities of Fluconazole and Voriconazole against 1,586 Recent Clinical Isolates of Candida Species Determined by Broth Microdilution, Disk Diffusion, and Etest Methods: Report from The ARTEMIS Global Antifungal Susceptibility Program, 2001. by Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153922

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Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. by Rogers TE, Galgiani JN.; 1986 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180572

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Activity of SCH 56592 compared with those of fluconazole and itraconazole against Candida spp. by Law D, Moore CB, Denning DW.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164118

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Addition of Caspofungin to Fluconazole Does Not Improve Outcome in Murine Candidiasis. by Graybill JR, Bocanegra R, Najvar LK, Hernandez S, Larsen RA.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161841

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Amphotericin B and Fluconazole Affect Cellular Charge, Macrophage Phagocytosis, and Cellular Morphology of Cryptococcus neoformans at Subinhibitory Concentrations. by Nosanchuk JD, Cleare W, Franzot SP, Casadevall A.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89056

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Amphotericin B Colloidal Dispersion Combined with Flucytosine with or without Fluconazole for Treatment of Murine Cryptococcal Meningitis. by Diamond DM, Bauer M, Daniel BE, Leal MA, Johnson D, Williams BK, Thomas AM, Ding JC, Najvar L, Graybill JR, Larsen RA.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105493

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Antagonistic effects of fluconazole and 5-fluorocytosine on candidacidal action of amphotericin B in human serum. by Martin E, Maier F, Bhakdi S.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188207

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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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Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. by Klepser ME, Wolfe EJ, Jones RN, Nightingale CH, Pfaller MA.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163923

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Antifungal Susceptibility Testing of Fluconazole by Flow Cytometry Correlates with Clinical Outcome. by Wenisch C, Moore CB, Krause R, Presterl E, Pichna P, Denning DW.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88170

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Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia. NIAID Mycoses Study Group and the Candidemia Study Group. by Rex JH, Pfaller MA, Barry AL, Nelson PW, Webb CD.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162481

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Antigen Clearance during Treatment of Disseminated Histoplasmosis with Itraconazole versus Fluconazole in Patients with AIDS. by Wheat LJ, Connolly P, Haddad N, Le Monte A, Brizendine E, Hafner R.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127009

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Assay of fluconazole by high-performance liquid chromatography with a mixedphase column. by Wallace JE, Harris SC, Gallegos J, Foulds G, Chen TJ, Rinaldi MG.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190563

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Assay of fluconazole by megabore capillary gas-liquid chromatography with nitrogen-selective detection. by Harris SC, Wallace JE, Foulds G, Rinaldi MG.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172520

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Assessment of Antifungal Activities of Fluconazole and Amphotericin B Administered Alone and in Combination against Candida albicans by Using a Dynamic In Vitro Mycotic Infection Model. by Lewis RE, Lund BC, Klepser ME, Ernst EJ, Pfaller MA.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105608

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Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. by Wingard JR, Merz WG, Rinaldi MG, Miller CB, Karp JE, Saral R.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188080

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Candida Isolates from Neonates: Frequency of Misidentification and Reduced Fluconazole Susceptibility. by Rowen JL, Tate JM, Nordoff N, Passarell L, McGinnis MR.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85744

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Characterization and Quantitation of the Pharmacodynamics of Fluconazole in a Neutropenic Murine Disseminated Candidiasis Infection Model. by Andes D, van Ogtrop M.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89432

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Characterization of Heteroresistance to Fluconazole among Clinical Isolates of Cryptococcus neoformans. by Yamazumi T, Pfaller MA, Messer SA, Houston AK, Boyken L, Hollis RJ, Furuta I, Jones RN.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149577

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Clonal and Spontaneous Origins of Fluconazole Resistance in Candida albicans. by Xu J, Ramos AR, Vilgalys R, Mitchell TG.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86380

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Colony Size Can Be Used To Determine the MIC of Fluconazole for Pathogenic Yeasts. by Xu J, Vilgalys R, Mitchell TG.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105058

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Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. by Sugar AM, Hitchcock CA, Troke PF, Picard M.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162590

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Combination therapy with amphotericin B and fluconazole against invasive candidiasis in neutropenic-mouse and infective-endocarditis rabbit models. by Sanati H, Ramos CF, Bayer AS, Ghannoum MA.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163912

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Combination therapy with fluconazole and flucytosine in the murine model of cryptococcal meningitis. by Nguyen MH, Najvar LK, Yu CY, Graybill JR.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163860

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Combined effect of fluconazole and recombinant human interleukin-1 on systemic candidiasis in neutropenic mice. by Kullberg BJ, van 't Wout JW, Poell RJ, van Furth R.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190322

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Combined therapy with fluconazole and flucytosine in murine cryptococcal meningitis. by Allendoerfer R, Marquis AJ, Rinaldi MG, Graybill JR.; 1991 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245086

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Comparative Efficacies of Terbinafine and Fluconazole in Treatment of Experimental Coccidioidal Meningitis in a Rabbit Model. by Sorensen KN, Sobel RA, Clemons KV, Calderon L, Howell KJ, Irani PR, Pappagianis D, Williams PL, Stevens DA.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101607

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Comparative evaluation of alternative methods for broth dilution susceptibility testing of fluconazole against Candida albicans. by Pfaller MA, Grant C, Morthland V, Rhine-Chalberg J.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263062

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Comparative evaluation of macrodilution and chromogenic agar screening for determining fluconazole susceptibility of Candida albicans. by Patterson TF, Kirkpatrick WR, Revankar SG, McAtee RK, Fothergill AW, McCarthy DI, Rinaldi MG.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229494

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Comparative Evaluation of National Committee for Clinical Laboratory Standards Broth Macrodilution and Agar Dilution Screening Methods for Testing Fluconazole Susceptibility of Cryptococcus neoformans. by Kirkpatrick WR, McAtee RK, Revankar SG, Fothergill AW, McCarthy DI, Rinaldi MG, Patterson TF.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104822

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Comparative evaluation of three antifungal susceptibility test methods for Candida albicans isolates and correlation with response to fluconazole therapy. by Ruhnke M, Schmidt-Westhausen A, Engelmann E, Trautmann M.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229485

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Comparative resistance of Candida albicans clinical isolates to fluconazole and itraconazole in vitro and in vivo in a murine model. by Valentin A, Le Guennec R, Rodriguez E, Reynes J, Mallie M, Bastide JM.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163328

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Comparison of a spectrophotometric microdilution method with RPMI-2% glucose with the National Committee for Clinical Laboratory Standards reference macrodilution method M27-P for in vitro susceptibility testing of amphotericin B, flucytosine, and fluconazole against Candida albicans. by Rodriguez-Tudela JL, Berenguer J, Martinez-Suarez JV, Sanchez R.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163462

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Comparison of D0870, a new triazole antifungal agent, to fluconazole for inhibition of Candida albicans cytochrome P-450 by using in vitro assays. by Venkateswarlu K, Denning DW, Manning NJ, Kelly SL.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163335

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Comparison of fluconazole and amphotericin B for prevention and treatment of experimental Candida endocarditis. by Witt MD, Bayer AS.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245416

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Comparison of fluconazole and amphotericin B for treatment of disseminated candidiasis and endophthalmitis in rabbits. by Filler SG, Crislip MA, Mayer CL, Edwards JE Jr.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=244993

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Comparison of fluconazole and amphotericin B for treatment of experimental Candida albicans endocarditis in rabbits. by Chemlal K, Saint-Julien L, Joly V, Farinotti R, Seta N, Yeni P, Carbon C.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163098

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Comparison of fluconazole and amphotericin B for treatment of experimental Candida endocarditis caused by non-C. albicans strains. by Witt MD, Imhoff T, Li C, Bayer AS.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188117

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Comparison of fluconazole and amphotericin B in prophylaxis of experimental Candida endocarditis caused by non-C. albicans strains. by Bayer AS, Witt MD, Kim E, Ghannoum MA.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163144

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Comparison of fluconazole and amphotericin B in treating histoplasmosis in immunosuppressed mice. by Kobayashi GS, Travis SJ, Medoff G.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175844

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Comparison of Fluconazole and Itraconazole in a Rabbit Model of Coccidioidal Meningitis. by Sorensen KN, Sobel RA, Clemons KV, Pappagianis D, Stevens DA, Williams PL.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89905

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Comparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomycosis. by Fierer J, Kirkland T, Finley F.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171511

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Comparison of in vivo activity of fluconazole with that of amphotericin B against Candida tropicalis, Candida glabrata, and Candida krusei. by Fisher MA, Shen SH, Haddad J, Tarry WF.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172680

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Comparison of itraconazole and fluconazole in treatment of cryptococcal meningitis and candida pyelonephritis in rabbits. by Perfect JR, Savani DV, Durack DT.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180445

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Comparison of oral fluconazole and clotrimazole troches as treatment for oral candidiasis in patients infected with human immunodeficiency virus. by Koletar SL, Russell JA, Fass RJ, Plouffe JF.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172036

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Comparison of Results Obtained by Testing with Three Different Agar Media and by the NCCLS M27-A Method for In Vitro Testing of Fluconazole against Candida spp. by Rubio MC, Gil J, de Ocariz IR, Benito R, Rezusta A.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156545

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Comparison of the in vitro activities of the echinocandin LY303366, the pneumocandin MK-0991, and fluconazole against Candida species and Cryptococcus neoformans. by Krishnarao TV, Galgiani JN.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164044

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Comparison of the Susceptibilities of Candida spp. to Fluconazole and Voriconazole in a 4-Year Global Evaluation Using Disk Diffusion. by Hazen KC, Baron EJ, Lopes Colombo A, Girmenia C, Sanchez-Sousa A, del Palacio A, de Bedout C, Gibbs DL.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=309015

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Comparison of Visual and Spectrophotometric Methods of Broth Microdilution MIC End Point Determination and Evaluation of a Sterol Quantitation Method for In Vitro

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Susceptibility Testing of Fluconazole and Itraconazole against Trailing and Nontrailing Candida Isolates. by Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, Harrison LH, Sofair AN, Warnock AD.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127334 •

Correlation between E-Test, Disk Diffusion, and Microdilution Methods for Antifungal Susceptibility Testing of Fluconazole and Voriconazole. by Matar MJ, Ostrosky-Zeichner L, Paetznick VL, Rodriguez JR, Chen E, Rex JH.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153338

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Correlation of Fluconazole MICs with Clinical Outcome in Cryptococcal Infection. by Aller AI, Martin-Mazuelos E, Lozano F, Gomez-Mateos J, Steele-Moore L, Holloway WJ, Gutierrez MJ, Recio FJ, Espinel-Ingroff A.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89910

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Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1. by Cameron ML, Schell WA, Bruch S, Bartlett JA, Waskin HA, Perfect JR.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192407

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Cyclic AMP and Fluconazole Resistance in Saccharomyces cerevisiae. by Kontoyiannis DP, Rupp S.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89950

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Demonstration of synergy with fluconazole and either ibuprofen, sodium salicylate, or propylparaben against Candida albicans in vitro. by Scott EM, Tariq VN, McCrory RM.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162998

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Different components in human serum inhibit multiplication of Cryptococcus neoformans and enhance fluconazole activity. by Nassar F, Brummer E, Stevens DA.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162970

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Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial Candida albicans Isolates from Human Immunodeficiency VirusInfected Patients with Oropharyngeal Candidiasis. by Lopez-Ribot JL, McAtee RK, Lee LN, Kirkpatrick WR, White TC, Sanglard D, Patterson TF.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105968

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Dynamic and Heterogeneous Mutations to Fluconazole Resistance in Cryptococcus neoformans. by Xu J, Onyewu C, Yoell HJ, Ali RY, Vilgalys RJ, Mitchell TG.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90307

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Effect of fluconazole on fungicidal activity of flucytosine in murine cryptococcal meningitis. by Larsen RA, Bauer M, Weiner JM, Diamond DM, Leal ME, Ding JC, Rinaldi MG, Graybill JR.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163494

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Effect of Fluconazole on Indinavir Pharmacokinetics in Human Immunodeficiency Virus-Infected Patients. by De Wit S, Debier M, De Smet M, McCrea J, Stone J, Carides A, Matthews C, Deutsch P, Clumeck N.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105391

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Effect of fluconazole on pharmacokinetics of 2',3'-dideoxyinosine in persons seropositive for human immunodeficiency virus. by Bruzzese VL, Gillum JG, Israel DS, Johnson GL, Kaplowitz LG, Polk RE.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162681

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Effect of Fluconazole on the Pharmacokinetics of Doxorubicin in Nonhuman Primates. by Warren KE, McCully CM, Walsh TJ, Balis FM.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89824

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Effect of fluconazole on the steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients. by Borin MT, Cox SR, Herman BD, Carel BJ, Anderson RD, Freimuth WW.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164031

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Effect of fluconazole on viability of Candida albicans over extended periods of time. by Sohnle PG, Hahn BL, Erdmann MD.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163587

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Effect of macrophage colony-stimulating factor on anticryptococcal activity of bronchoalveolar macrophages: synergy with fluconazole for killing. by Brummer E, Nassar F, Stevens DA.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284700

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Effect of Prolonged Fluconazole Treatment on Candida albicans in Diffusion Chambers Implanted into Mice. by Sohnle PG, Hahn BL.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128792

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Effect of severity of meningitis on fungicidal activity of flucytosine combined with fluconazole in a murine model of cryptococcal meningitis. by Ding JC, Bauer M, Diamond DM, Leal MA, Johnson D, Williams BK, Thomas AM, Najvar L, Graybill JR, Larsen RA.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163965

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Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans. by van Etten EW, van de Rhee NE, van Kampen KM, Bakker-Woudenberg IA.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245371

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Effects of Cytokines and Fluconazole on the Activity of Human Monocytes against Candida albicans. by Baltch AL, Smith RP, Franke MA, Ritz WJ, Michelsen PB, Bopp LH.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90246

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Effects of Fluconazole and Clarithromycin on Rifabutin and 25-O-Desacetylrifabutin Pharmacokinetics. by Jordan MK, Polis MA, Kelly G, Narang PK, Masur H, Piscitelli SC.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90031

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Efficacies of High-Dose Fluconazole plus Amphotericin B and High-Dose Fluconazole plus 5-Fluorocytosine versus Amphotericin B, Fluconazole, and 5Fluorocytosine Monotherapies in Treatment of Experimental Endocarditis, Endophthalmitis, and Pyelonephritis Due to Candida albicans. by Louie A, Liu W, Miller DA, Sucke AC, Liu QF, Drusano GL, Mayers M, Miller MH.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89573

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Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis. by Clemons KV, Hanson LH, Perlman AM, Stevens DA.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171724

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Evaluation of Etest Method for Determining Fluconazole and Voriconazole MICs for 279 Clinical Isolates of Candida Species Infrequently Isolated from Blood. by Maxwell MJ, Messer SA, Hollis RJ, Boyken L, Tendolkar S, Diekema DJ, Pfaller MA.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150324

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Evaluation of the Etest and Disk Diffusion Methods for Determining Susceptibilities of 235 Bloodstream Isolates of Candida glabrata to Fluconazole and Voriconazole. by Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154736

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Evaluation of the Etest Method for Determining Fluconazole Susceptibilities of 402 Clinical Yeast Isolates by Using Three Different Agar Media. by Pfaller MA, Messer SA, Karlsson A, Bolmstrom A.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105167

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Experimental Induction of Fluconazole Resistance in Candida tropicalis ATCC 750. by Barchiesi F, Calabrese D, Sanglard D, Falconi Di Francesco L, Caselli F, Giannini D, Giacometti A, Gavaudan S, Scalise G.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89916

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Flucytosine-Fluconazole Cross-Resistance in Purine-Cytosine Permease-Deficient Candida lusitaniae Clinical Isolates: Indirect Evidence of a Fluconazole Uptake Transporter. by Noel T, Francois F, Paumard P, Chastin C, Brethes D, Villard J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152504

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Fungicidal Activity of Fluconazole against Candida albicans in a Synthetic VaginaSimulative Medium. by Moosa MY, Sobel JD, Elhalis H, Du W, Akins RA.; 2004 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=310176

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Fungicidal Synergism of Fluconazole and Cyclosporine in Candida albicans Is Not Dependent on Multidrug Efflux Transporters Encoded by the CDR1, CDR2, CaMDR1, and FLU1 Genes. by Marchetti O, Moreillon P, Entenza JM, Vouillamoz J, Glauser MP, Bille J, Sanglard D.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153326

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G484S Amino Acid Substitution in Lanosterol 14-[alpha] Demethylase (ERG11) Is Related to Fluconazole Resistance in a Recurrent Cryptococcus neoformans Clinical Isolate. by Rodero L, Mellado E, Rodriguez AC, Salve A, Guelfand L, Cahn P, CuencaEstrella M, Davel G, Rodriguez-Tudela JL.; 2003 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=253790

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Genetic Basis for Differential Activities of Fluconazole and Voriconazole against Candida krusei. by Fukuoka T, Johnston DA, Winslow CA, de Groot MJ, Burt C, Hitchcock CA, Filler SG.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152512

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Heteroresistance to Fluconazole and Voriconazole in Cryptococcus neoformans. by Mondon P, Petter R, Amalfitano G, Luzzati R, Concia E, Polacheck I, Kwon-Chung KJ.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89380

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Hospital Specificity, Region Specificity, and Fluconazole Resistance of Candida albicans Bloodstream Isolates. by Pfaller MA, Lockhart SR, Pujol C, Swails-Wenger JA, Messer SA, Edmond MB, Jones RN, Wenzel RP, Soll DR.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104870

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Hypothesis on the mechanism of resistance to fluconazole in Histoplasma capsulatum. by Wheat J, Marichal P, Vanden Bossche H, Le Monte A, Connolly P.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163721

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Identification and Expression of Multidrug Transporters Responsible for Fluconazole Resistance in Candida dubliniensis. by Moran GP, Sanglard D, Donnelly SM, Shanley DB, Sullivan DJ, Coleman DC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105690

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Identification of Major Glucan-Associated Cell Wall Proteins of Candida albicans and Their Role in Fluconazole Resistance. by Angiolella L, Micocci MM, D'Alessio S, Girolamo A, Maras B, Cassone A.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127269

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Immunization with the Candida albicans Membrane Fraction and in Combination with Fluconazole Protects against Systemic Fungal Infections. by Mizutani S, Endo M, Ino-ue T, Kurasawa M, Uno Y, Saito H, Kato I, Takesako K.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89665

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Impact of the Order of Initiation of Fluconazole and Amphotericin B in Sequential or Combination Therapy on Killing of Candida albicans In Vitro and in a Rabbit Model of Endocarditis and Pyelonephritis. by Louie A, Kaw P, Banerjee P, Liu W, Chen G, Miller MH.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90317

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Improved medium for fluconazole susceptibility testing of Candida albicans. by Rodriguez-Tudela JL, Martinez-Suarez JV.; 1994 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284394

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In Vitro Activities of Caspofungin Compared with Those of Fluconazole and Itraconazole against 3,959 Clinical Isolates of Candida spp., Including 157 Fluconazole-Resistant Isolates. by Pfaller MA, Diekema DJ, Messer SA, Hollis RJ, Jones RN.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149290

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In Vitro Activities of Posaconazole (Sch 56592) Compared with Those of Itraconazole and Fluconazole against 3,685 Clinical Isolates of Candida spp. and Cryptococcus neoformans. by Pfaller MA, Messer SA, Hollis RJ, Jones RN.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90743

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In vitro activities of terbinafine in combination with fluconazole and itraconazole against isolates of Candida albicans with reduced susceptibility to azoles. by Barchiesi F, Falconi Di Francesco L, Scalise G.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164012

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In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates. by Uzun O, Kocagoz S, Cetinkaya Y, Arikan S, Unal S.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163869

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In vitro activity of BMS-181184 compared with those of fluconazole and amphotericin B against various candida spp. by Wardle HM, Law D, Denning DW.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163508

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In Vitro Activity of Nystatin Compared with Those of Liposomal Nystatin, Amphotericin B, and Fluconazole against Clinical Candida Isolates. by Arikan S, Ostrosky-Zeichner L, Lozano-Chiu M, Paetznick V, Gordon D, Wallace T, Rex JH.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140327

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In vitro and in vivo antifungal activities of DU-6859a, a fluoroquinolone, in combination with amphotericin B and fluconazole against pathogenic fungi. by Nakajima R, Kitamura A, Someya K, Tanaka M, Sato K.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162773

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In Vitro Antifungal Activity of Nikkomycin Z in Combination with Fluconazole or Itraconazole. by Li RK, Rinaldi MG.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89286

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In vitro evaluation of combination of fluconazole and flucytosine against Cryptococcus neoformans var. neoformans. by Nguyen MH, Barchiesi F, McGough DA, Yu VL, Rinaldi MG.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162809

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In Vitro Interaction of Flucytosine Combined with Amphotericin B or Fluconazole against Thirty-Five Yeast Isolates Determined by both the Fractional Inhibitory Concentration Index and the Response Surface Approach. by Te Dorsthorst DT, Verweij PE, Meletiadis J, Bergervoet M, Punt NC, Meis JF, Mouton JW.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127432

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Induction potential of fluconazole toward drug-metabolizing enzymes in rats. by Lavrijsen KL, Van Houdt JM, Van Dyck DM, Meuldermans WE, Heykants JJ.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171605

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Influence of local radiotherapy on penetration of fluconazole into human saliva. by Oliary J, Tod M, Louchahi K, Petitjean O, Frachet B, Le Gros V, Brion N.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192775

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Interaction between Fluconazole and Amphotericin B in Mice with Systemic Infection Due to Fluconazole-Susceptible or -Resistant Strains of Candida albicans. by Louie A, Banerjee P, Drusano GL, Shayegani M, Miller MH.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89574

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Isolation of Candida species on media with and without added fluconazole reveals high variability in relative growth susceptibility phenotypes. by Schoofs A, Odds FC, Colebunders R, Ieven M, Wouters L, Goossens H.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163976

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Mechanism of Fluconazole Resistance in Candida albicans Biofilms: Phase-Specific Role of Efflux Pumps and Membrane Sterols. by Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165995

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Mechanism of Fluconazole Resistance in Candida krusei. by Orozco AS, Higginbotham LM, Hitchcock CA, Parkinson T, Falconer D, Ibrahim AS, Ghannoum MA, Filler SG.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105912

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Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B. by Ghannoum MA, Filler SG, Ibrahim AS, Fu Y, Edwards JE Jr.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245483

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Molecular epidemiology of Candida isolates from AIDS patients showing different fluconazole resistance profiles. by Lischewski A, Ruhnke M, Tennagen I, Schonian G, Morschhauser J, Hacker J.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228034

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Molecular Mechanisms of Fluconazole Resistance in Candida dubliniensis Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis. by Perea S, Lopez-Ribot JL, Wickes BL, Kirkpatrick WR, Dib OP, Bachmann SP, Keller SM, Martinez M, Patterson TF.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127221

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Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy. by Mukherjee J, Feldmesser M, Scharff MD, Casadevall A.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162752

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Multicenter Comparative Evaluation of Six Commercial Systems and the National Committee for Clinical Laboratory Standards M27-A Broth Microdilution Method for

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Fluconazole Susceptibility Testing of Candida Species. by Morace G, Amato G, Bistoni F, Fadda G, Marone P, Montagna MT, Oliveri S, Polonelli L, Rigoli R, Mancuso I, La Face S, Masucci L, Romano L, Napoli C, Tato D, Buscema MG, Belli CM, Piccirillo MM, Conti S, Covan S, Fanti F, Cavanna C, D'Alo F, Pitzurra L.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120637 •

Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. by Albertson GD, Niimi M, Cannon RD, Jenkinson HF.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163632

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Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical Candida albicans Strains. by Franz R, Kelly SL, Lamb DC, Kelly DE, Ruhnke M, Morschhauser J.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106000

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Multiple Patterns of Resistance to Fluconazole in Candida glabrata Isolates from a Patient with Oropharyngeal Candidiasis Receiving Head and Neck Radiation. by Redding SW, Kirkpatrick WR, Saville S, Coco BJ, White W, Fothergill A, Rinaldi M, Eng T, Patterson TF, Lopez-Ribot J.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149712

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Novel Fluorescent Broth Microdilution Method for Fluconazole Susceptibility Testing of Candida albicans. by Liao RS, Rennie RP, Talbot JA.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88218

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Optimizing the Correlation between Results of Testing In Vitro and Therapeutic Outcome In Vivo for Fluconazole by Testing Critical Isolates in a Murine Model of Invasive Candidiasis. by Rex JH, Nelson PW, Paetznick VL, Lozano-Chiu M, EspinelIngroff A, Anaissie EJ.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105467

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Optimizing Voriconazole Susceptibility Testing of Candida: Effects of Incubation Time, Endpoint Rule, Species of Candida, and Level of Fluconazole Susceptibility. by Lozano-Chiu M, Arikan S, Paetznick VL, Anaissie EJ, Rex JH.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85370

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Overexpression of Erg11p by the Regulatable GAL1 Promoter Confers Fluconazole Resistance in Saccharomyces cerevisiae. by Kontoyiannis DP, Sagar N, Hirschi KD.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89564

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Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain. by Martinez-Suarez JV, Rodriguez-Tudela JL.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162772

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Penetration of Oral Fluconazole into Gynecological Tissues. by Mikamo H, Kawazoe K, Sato Y, Izumi K, Ito T, Ito K, Tamaya T.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89035

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Persistence of Oropharyngeal Candida albicans Strains with Reduced Susceptibilities to Fluconazole among Human Immunodeficiency Virus-Seropositive Children and Adults in a Long-Term Care Facility. by Makarova NU, Pokrowsky VV, Kravchenko AV, Serebrovskaya LV, James MJ, McNeil MM, Lasker BA, Warnock DW, Reiss E.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154751

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Pharmacodynamics of Fluconazole in a Murine Model of Systemic Candidiasis. by Louie A, Drusano GL, Banerjee P, Liu QF, Liu W, Kaw P, Shayegani M, Taber H, Miller MH.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105753

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Pharmacokinetic Studies of Fluconazole in Rabbits Characterizing Doses Which Achieve Peak Levels in Serum and Area under the Concentration-Time Curve Values Which Mimic Those of High-Dose Fluconazole in Humans. by Louie A, Liu QF, Drusano GL, Liu W, Mayers M, Anaissie E, Miller MH.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105634

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Pharmacokinetics and bioavailability of fluconazole in patients with AIDS. by DeMuria D, Forrest A, Rich J, Scavone JM, Cohen LG, Kazanjian PH.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192248

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Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. by Tett S, Moore S, Ray J.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162835

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Pharmacokinetics and tissue penetration of fluconazole in rabbits. by Walsh TJ, Foulds G, Pizzo PA.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172461

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Pharmacokinetics of 18F-labeled fluconazole in healthy human subjects by positron emission tomography. by Fischman AJ, Alpert NM, Livni E, Ray S, Sinclair I, Callahan RJ, Correia JA, Webb D, Strauss HW, Rubin RH.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187952

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Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. by Tucker RM, Williams PL, Arathoon EG, Levine BE, Hartstein AI, Hanson LH, Stevens DA.; 1988 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172178

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Pharmacokinetics of fluconazole in cerebrospinal fluid and serum of rabbits: validation of an animal model used to measure drug concentrations in cerebrospinal fluid. by Madu A, Cioffe C, Mian U, Burroughs M, Tuomanen E, Mayers M, Schwartz E, Miller M.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284693

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Pharmacokinetics of fluconazole in saliva and plasma after administration of an oral suspension and capsules. by Koks CH, Meenhorst PL, Hillebrand MJ, Bult A, Beijnen JH.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163444

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Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients. by El-Yazigi A, Ellis M, Ernst P, Spence D, Hussain R, Baillie FJ.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163824

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Pneumocandin L-743,872 enhances the activities of amphotericin B and fluconazole against Cryptococcus neoformans in vitro. by Franzot SP, Casadevall A.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163710

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Potent Synergism of the Combination of Fluconazole and Cyclosporine in Candida albicans. by Marchetti O, Moreillon P, Glauser MP, Bille J, Sanglard D.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90072

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Precision and Accuracy of Fluconazole Susceptibility Testing by Broth Microdilution, Etest, and Disk Diffusion Methods. by Barry AL, Pfaller MA, Rennie RP, Fuchs PC, Brown SD.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127270

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Prevalence of Molecular Mechanisms of Resistance to Azole Antifungal Agents in Candida albicans Strains Displaying High-Level Fluconazole Resistance Isolated from Human Immunodeficiency Virus-Infected Patients. by Perea S, Lopez-Ribot JL, Kirkpatrick WR, McAtee RK, Santillan RA, Martinez M, Calabrese D, Sanglard D, Patterson TF.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90716

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Prospective, Multicenter Surveillance Study of Candida glabrata: Fluconazole and Itraconazole Susceptibility Profiles in Bloodstream, Invasive, and Colonizing Strains and Differences between Isolates from Three Urban Teaching Hospitals in New York City (Candida Susceptibility Trends Study, 1998 to 1999). by Safdar A, Chaturvedi V, Koll BS, Larone DH, Perlin DS, Armstrong D.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128796

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Quality Control Limits for Fluconazole Disk Susceptibility Tests on Mueller-Hinton Agar with Glucose and Methylene Blue. by Barry A, Bille J, Brown S, Ellis D, Meis J, Pfaller M, Rennie R, Rinaldi M, Rogers T, Traczewski M.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165306

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Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis. by ArthingtonSkaggs BA, Warnock DW, Morrison CJ.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90017

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Quantitation of Ergosterol Content: Novel Method for Determination of Fluconazole Susceptibility of Candida albicans. by Arthington-Skaggs BA, Jradi H, Desai T, Morrison CJ.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85559

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Random Amplification of Polymorphic DNA and Microsatellite Genotyping of Preand Posttreatment Isolates of Candida spp. from Human Immunodeficiency Virus-

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Infected Patients on Different Fluconazole Regimens. by Metzgar D, van Belkum A, Field D, Haubrich R, Wills C.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105037 •

Rapid and sensitive assay for fluconazole which uses gas chromatography with electron capture detection. by Rege AB, Walker-Cador JY, Clark RA, Lertora JJ, Hyslop NE Jr, George WJ.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190572

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Rapid, Transient Fluconazole Resistance in Candida albicans Is Associated with Increased mRNA Levels of CDR. by Marr KA, Lyons CN, Rustad T, Bowden RA, White TC.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105901

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Response to fluconazole by 23 patients with human immunodeficiency virus infection and oral candidiasis: pharmacological and mycological factors. by Lacassin F, Damond F, Chochillon C, Longuet P, Lebras J, Vilde JL, Leport C.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163452

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Reversible fluconazole resistance in Candida albicans: a potential in vitro model. by Calvet HM, Yeaman MR, Filler SG.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163746

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Safety and Tolerability of Fluconazole in Children. by Novelli V, Holzel H.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89397

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Sensitive Bioassay for Determination of Fluconazole Concentrations in Plasma Using a Candida albicans Mutant Hypersusceptible to Azoles. by Marchetti O, Majcherczyk PA, Glauser MP, Bille J, Moreillon P, Sanglard D.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90358

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Sputum levels of fluconazole in humans. by Ebden P, Neill P, Farrow PR.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284264

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Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography. by Rex JH, Hanson LH, Amantea MA, Stevens DA, Bennett JE.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245118

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Successful Treatment of Fluconazole-Resistant Oropharyngeal Candidiasis by a Combination of Fluconazole and Terbinafine. by Ghannoum MA, Elewski B.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95798

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Susceptibility Testing of Fluconazole by the NCCLS Broth Macrodilution Method, ETest, and Disk Diffusion for Application in the Routine Laboratory. by Vandenbossche I, Vaneechoutte M, Vandevenne M, De Baere T, Verschraegen G.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120224

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Synergistic Activity of the N-Terminal Peptide of Human Lactoferrin and Fluconazole against Candida Species. by Lupetti A, Paulusma-Annema A, Welling

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MM, Dogterom-Ballering H, Brouwer CP, Senesi S, van Dissel JT, Nibbering PH.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149030 •

The Candida dubliniensis CdCDR1 Gene Is Not Essential for Fluconazole Resistance. by Moran G, Sullivan D, Morschhauser J, Coleman D.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127416

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Uptake and intracellular activity of fluconazole in human polymorphonuclear leukocytes. by Pascual A, Garcia I, Conejo C, Perea EJ.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187636

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Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS. by Berry AJ, Rinaldi MG, Graybill JR.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190584

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Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model. by Barchiesi F, Najvar LK, Luther MF, Scalise G, Rinaldi MG, Graybill JR.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163320

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Variation in Susceptibility of Bloodstream Isolates of Candida glabrata to Fluconazole According to Patient Age and Geographic Location. by Pfaller MA, Messer SA, Boyken L, Tendolkar S, Hollis RJ, Diekema DJ.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154732

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Variations in fluconazole susceptibility and DNA subtyping of multiple Candida albicans colonies from patients with AIDS and oral candidiasis suffering one or more episodes of infection. by Redding SW, Pfaller MA, Messer SA, Smith JA, Prows J, Bradley LL, Fothergill AW, Rinaldi MG.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229836

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Variations in fluconazole susceptibility and electrophoretic karyotype among oral isolates of Candida albicans from patients with AIDS and oral candidiasis. by Pfaller MA, Rhine-Chalberg J, Redding SW, Smith J, Farinacci G, Fothergill AW, Rinaldi MG.; 1994 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262970

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

A case of HIV-associated cerebral histoplasmosis successfully treated with fluconazole. Author(s): Knapp S, Turnherr M, Dekan G, Willinger B, Stingl G, Rieger A. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 September; 18(9): 658-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534189

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A comparative study of the efficacy and safety of fluconazole oral suspension and amphotericin B oral suspension in cancer patients with mucositis. Author(s): Lefebvre JL, Domenge C; Study Group of Mucositis. Source: Oral Oncology. 2002 June; 38(4): 337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076696

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A comparison of fluconazole oral suspension and amphotericin B oral suspension in older patients with oropharyngeal candidosis. Multicentre Study Group. Author(s): Taillandier J, Esnault Y, Alemanni M. Source: Age and Ageing. 2000 March; 29(2): 117-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10791445

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A double-blind comparison of fluconazole and nystatin in the prevention of candidiasis in patients with leukaemia. Antifungal Prophylaxis Study Group. Author(s): Young GA, Bosly A, Gibbs DL, Durrant S. Source: European Journal of Cancer (Oxford, England : 1990). 1999 August; 35(8): 120813. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10615231

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A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis. Author(s): Havu V, Heikkila H, Kuokkanen K, Nuutinen M, Rantanen T, Saari S, Stubb S, Suhonen R, Turjanmaa K. Source: The British Journal of Dermatology. 2000 January; 142(1): 97-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10651701

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A global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion. Global Antifungal Surveillance Group. Author(s): Meis J, Petrou M, Bille J, Ellis D, Gibbs D. Source: Diagnostic Microbiology and Infectious Disease. 2000 April; 36(4): 215-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10764963

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A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Author(s): Rex JH, Pappas PG, Karchmer AW, Sobel J, Edwards JE, Hadley S, Brass C, Vazquez JA, Chapman SW, Horowitz HW, Zervos M, McKinsey D, Lee J, Babinchak T, Bradsher RW, Cleary JD, Cohen DM, Danziger L, Goldman M, Goodman J, Hilton E, Hyslop NE, Kett DH, Lutz J, Rubin RH, Scheld WM, Schuster M, Simmons B, Stein DK, Washburn RG, Mautner L, Chu TC, Panzer H, Rosenstein RB, Booth J; National Institute of Allergy and Infectious Diseases Mycoses Study Group. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 May 15; 36(10): 1221-8. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746765

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A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Author(s): Villanueva A, Gotuzzo E, Arathoon EG, Noriega LM, Kartsonis NA, Lupinacci RJ, Smietana JM, DiNubile MJ, Sable CA. Source: The American Journal of Medicine. 2002 September; 113(4): 294-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12361815

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Absence of clinically relevant drug interactions following simultaneous administration of didanosine-encapsulated, enteric-coated bead formulation with either itraconazole or fluconazole. Author(s): Damle B, Hess H, Kaul S, Knupp C. Source: Biopharmaceutics & Drug Disposition. 2002 March; 23(2): 59-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932960

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Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by Broth microdilution, disk diffusion, and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001. Author(s): Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ. Source: Journal of Clinical Microbiology. 2003 April; 41(4): 1440-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682127

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Acute generalized exanthematous pustulosis induced by oral fluconazole. Author(s): Alsadhan A, Taher M, Krol A. Source: Journal of Cutaneous Medicine and Surgery. 2002 March-April; 6(2): 122-4. Epub 2002 February 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992184

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Acute hepatitis and rash to fluconazole. Author(s): Su FW, Perumalswami P, Grammer LC. Source: Allergy. 2003 November; 58(11): 1215-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616149

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Adherence of different Candida dubliniensis isolates in the presence of fluconazole. Author(s): Borg-von Zepelin M, Niederhaus T, Gross U, Seibold M, Monod M, Tintelnot K. Source: Aids (London, England). 2002 June 14; 16(9): 1237-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12045488

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Amphotericin B versus fluconazole for controlling fungal infections in neutropenic cancer patients. Author(s): Johansen HK, Gotzsche PC. Source: Cochrane Database Syst Rev. 2002; (2): Cd000239. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076388

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An open, randomized, comparative study of oral fluconazole, itraconazole and terbinafine therapy in onychomycosis. Author(s): Arca E, Tastan HB, Akar A, Kurumlu Z, Gur AR. Source: The Journal of Dermatological Treatment. 2002 March; 13(1): 3-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006131

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Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafungin (LY 303366) alone and in combination against Candida spp. and Crytococcus neoformans via time-kill methods. Author(s): Roling EE, Klepser ME, Wasson A, Lewis RE, Ernst EJ, Pfaller MA. Source: Diagnostic Microbiology and Infectious Disease. 2002 May; 43(1): 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052624

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Antifungal prophylaxis with low doses fluconazole in patients with hematological malignancies. Author(s): Goranov S, Spasov E, Grudeva-Popova J, Vakrilov V. Source: Folia Med (Plovdiv). 1999; 41(4): 68-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10786208

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Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia? Author(s): Kovacicova G, Krupova Y, Lovaszova M, Roidova A, Trupl J, Liskova A, Hanzen J, Milosovic P, Lamosova M, Macekova L, Szovenyiova Z, Purgelova A, Obertik T, Bille J, Krcmery V. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2000 December; 6(4): 216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810569

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Biliary concentrations of fluconazole in a patient with candidal cholecystitis: case report. Author(s): Bozzette SA, Gordon RL, Yen A, Rinaldi M, Ito MK, Fierer J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1992 October; 15(4): 701-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1420685

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Bioavailability of fluconazole administered via a feeding tube in intensive care unit patients. Author(s): Nicolau DP, Crowe H, Nightingale CH, Quintiliani R. Source: The Journal of Antimicrobial Chemotherapy. 1995 August; 36(2): 395-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8522469

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Bioavailability of fluconazole and ketoconazole in human stratum corneum and oral mucosa. Author(s): Pierard GE, Rurangirwa A, Pierard-Franchimont C. Source: Clinical and Experimental Dermatology. 1991 May; 16(3): 168-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1934566

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Bioavailability of fluconazole in surgical intensive care unit patients: a study comparing routes of administration. Author(s): Rosemurgy AS, Markowsky S, Goode SE, Plastino K, Kearney RE. Source: The Journal of Trauma. 1995 September; 39(3): 445-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7473906

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Bioavailability of fluconazole in the skin after oral medication. Author(s): Wildfeuer A, Faergemann J, Laufen H, Pfaff G, Zimmermann T, Seidl HP, Lach P. Source: Mycoses. 1994 March-April; 37(3-4): 127-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7845418

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Bioequivalence study of two fluconazole capsule formulations in healthy volunteers. Author(s): Pereira R, Fidelis S, Vanunci ML, Oliveira CH, Mendes GD, Abib E, Moreno RA. Source: Int J Clin Pharmacol Ther. 2004 January; 42(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756386

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Breakthrough candidaemias during empirical therapy with fluconazole in non-cancer and non-HIV adults caused by in vitro-susceptible Candida spp.: report of 33 cases. Author(s): Kovacicova G, Mateicka F, Hanzen J, Liskova A, Sabo A, Szovenyova Z, Chmelik B, Huttova M, Krcmery V. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(10): 749-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728041

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Breakthrough candidemia during antifungal treatment with fluconazole in patients with hematologic malignancies. Author(s): Girmenia C, Martino P, Cassone A. Source: Blood. 1996 January 15; 87(2): 838-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555510

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Breakthrough fungaemia in neonates and infants caused by Candida albicans and Candida parapsilosis susceptible to fluconazole in vitro. Author(s): Krcmery V, Huttova M, Mateicka F, Laho L, Jurga L, Ondrusova A, Tarekova Z, Kralinsky K, Hanzen J, Liskova A, Mrazova M, Sabo A, Pisarcikova M, Kovacicova G, Chovancova D, Szovenyiova Z. Source: The Journal of Antimicrobial Chemotherapy. 2001 October; 48(4): 521-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11581231

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Breast pain during lactation that resolved with fluconazole: two case studies. Author(s): Hoover K. Source: Journal of Human Lactation : Official Journal of International Lactation Consultant Association. 1999 June; 15(2): 98-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10578783

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Candida isolates from neonates: frequency of misidentification and reduced fluconazole susceptibility. Author(s): Rowen JL, Tate JM, Nordoff N, Passarell L, McGinnis MR. Source: Journal of Clinical Microbiology. 1999 November; 37(11): 3735-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10523588

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Candida lusitaniae infections in the era of fluconazole availability. Author(s): Hawkins JL, Baddour LM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 January 15; 36(2): E14-8. Epub 2003 Jan 03. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522762

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Candida peritonitis due to peptic ulcer perforation: incidence rate, risk factors, prognosis and susceptibility to fluconazole and amphotericin B. Author(s): Lee SC, Fung CP, Chen HY, Li CT, Jwo SC, Hung YB, See LC, Liao HC, Loke SS, Wang FL, Lee JC. Source: Diagnostic Microbiology and Infectious Disease. 2002 September; 44(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376027

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Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. Author(s): Marr KA, Seidel K, White TC, Bowden RA. Source: The Journal of Infectious Diseases. 2000 January; 181(1): 309-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10608780

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Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Author(s): Sobel JD, Kauffman CA, McKinsey D, Zervos M, Vazquez JA, Karchmer AW, Lee J, Thomas C, Panzer H, Dismukes WE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 January; 30(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10619727

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Caspofungin activity against clinical isolates of fluconazole-resistant Candida. Author(s): Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Diekema DJ. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5729-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662968

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Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans. Author(s): Yamazumi T, Pfaller MA, Messer SA, Houston AK, Boyken L, Hollis RJ, Furuta I, Jones RN. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 267-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517859

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Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative. Author(s): Niimi K, Harding DR, Parshot R, King A, Lun DJ, Decottignies A, Niimi M, Lin S, Cannon RD, Goffeau A, Monk BC. Source: Antimicrobial Agents and Chemotherapy. 2004 April; 48(4): 1256-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15047528

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Clinical factors associated with fluconazole resistance and short-term survival in patients with Candida bloodstream infection. Author(s): Takakura S, Fujihara N, Saito T, Kudo T, Iinuma Y, Ichiyama S; Japan Invasive Mycosis Surveillance Study Group. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2004 May; 23(5): 380-8. Epub 2004 April 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15112070

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Clinical features and treatment of Malassezia folliculitis with fluconazole in orthotopic heart transplant recipients. Author(s): Rhie S, Turcios R, Buckley H, Suh B. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 February; 19(2): 215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703699

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Clinical resistance of recurrent Candida albicans vulvovaginitis to fluconazole in the presence and absence of in vitro resistance. Author(s): MacNeill C, Weisz J, Carey JC. Source: J Reprod Med. 2003 February; 48(2): 63-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621787

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Clonal and spontaneous origins of fluconazole resistance in Candida albicans. Author(s): Xu J, Ramos AR, Vilgalys R, Mitchell TG. Source: Journal of Clinical Microbiology. 2000 March; 38(3): 1214-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10699025

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Combined action of fluconazole and PMNs from uremic patients in clearing intracellular Candida albicans. Author(s): Tullio V, Cuffini AM, Giacchino F, Mandras N, Roana J, Comune L, Merlino C, Carlone NA. Source: J Chemother. 2003 June; 15(3): 301-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868562

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Comparison of fluconazole and nystatin oral suspensions for treatment of oral candidiasis in infants. Author(s): Goins RA, Ascher D, Waecker N, Arnold J, Moorefield E. Source: The Pediatric Infectious Disease Journal. 2002 December; 21(12): 1165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12506950

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Comparison of results obtained by testing with three different agar media and by the NCCLS M27-A method for in vitro testing of fluconazole against Candida spp. Author(s): Rubio MC, Gil J, De Ocariz IR, Benito R, Rezusta A. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2665-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791899

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Comparison of the susceptibilities of Candida spp. to fluconazole and voriconazole in a 4-year global evaluation using disk diffusion. Author(s): Hazen KC, Baron EJ, Colombo AL, Girmenia C, Sanchez-Sousa A, del Palacio A, de Bedout C, Gibbs DL; Global Antifungal Surveillance Group. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5623-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662952

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Correlation of in vitro itraconazole and fluconazole susceptibility with clinical outcome for patients with vulvovaginal candidiasis. Author(s): Costa M, Passos XS, Miranda AT, de Araujo RS, Paula CR, Silva Mdo R. Source: Mycopathologia. 2004 January; 157(1): 43-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008344

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Cryptococcus neoformans var neoformans resistant to fluconazole in an HIV-negative patient with chronic lymphocytic leukemia. Author(s): Assing K, Birgens H, Arendrup M. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 May; 9(5): 441-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848761

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Current status and fluconazole treatment of pelvic fungal gynecological infections. Author(s): Mikamo H, Sato Y, Hayasaki Y, Tamaya T. Source: Chemotherapy. 2000 May-June; 46(3): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765038

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Debilitating folliculitis barbae candidomycetica in a trumpeter: successful treatment with fluconazole. Author(s): Kick G, Korting HC. Source: Mycoses. 1998 September-October; 41(7-8): 339-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9861841

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Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency virus-infected patients. Author(s): Martins MD, Lozano-Chiu M, Rex JH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 November; 27(5): 1291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9827284

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Decrease in Candida albicans strains with reduced susceptibility to fluconazole following changes in prescribing policies. Author(s): Lopez J, Pernot C, Aho S, Caillot D, Vagner O, Dalle F, Durnet-Archeray MJ, Chavanet P, Bonnin A. Source: The Journal of Hospital Infection. 2001 June; 48(2): 122-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11428879

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Delay of onset of candidemia and emergence of Candida krusei fungemia in hematologic patients receiving prophylactic fluconazole. Author(s): Jarque I, Saavedra S, Martin G, Peman J, Perez Belles C, Sanz MA. Source: Haematologica. 2000 April; 85(4): 441-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10757896

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Delirium associated with amitriptyline/fluconazole drug. Author(s): Duggal HS. Source: General Hospital Psychiatry. 2003 July-August; 25(4): 297-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850665

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Desenitization to fluconazole in an AIDS patient. Author(s): Takahashi T, Hitani A, Yamada H, Nakamura T, Iwamoto A. Source: The Annals of Pharmacotherapy. 2001 May; 35(5): 642-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346073

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Detection of fluconazole-resistant Candida strains by a disc diffusion screening test. Author(s): Sandven P. Source: Journal of Clinical Microbiology. 1999 December; 37(12): 3856-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565896

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Detection of fluconazole-resistant isolates of Candida glabrata by using an agar screen assay. Author(s): Nelson SM, Cartwright CP. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2141-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734262

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Determinants for the development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients. Author(s): Masia Canuto M, Gutierrez Rodero F, Ortiz de la Tabla Ducasse V, Hernandez Aguado I, Martin Gonzalez C, Sanchez Sevillano A, Martin Hidalgo A. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2000 August; 19(8): 593601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11014621

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Developing and implementing guidelines to promote appropriate use of fluconazole therapy in an AIDS clinic. Author(s): Anassi EO, Egbunike IG, Akpaffiong MJ, Ike EN, Cate TR. Source: Hosp Pharm. 1994 June; 29(6): 576-8, 581-2, 585-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10134178

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Development of azole resistance during fluconazole maintenance therapy for AIDSassociated cryptococcal disease. Author(s): Friese G, Discher T, Fussle R, Schmalreck A, Lohmeyer J. Source: Aids (London, England). 2001 November 23; 15(17): 2344-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11698718

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Development of secondary resistance to fluconazole in Cryptococcus neoformans isolated from a patient with AIDS. Author(s): Alves SH, Lopes JO, Costa JM, Klock C. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 1997 NovemberDecember; 39(6): 359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9674289

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Development of simultaneous resistance to fluconazole in Candida albicans and Candida dubliniensis in a patient with AIDS. Author(s): Ruhnke M, Schmidt-Westhausen A, Morschhauser J. Source: The Journal of Antimicrobial Chemotherapy. 2000 August; 46(2): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933656

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Disk diffusion method for fluconazole susceptibility testing of Candida albicans strains. Author(s): Yucesoy M, Guldas NS, Yulug N. Source: J Chemother. 2001 April; 13(2): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11330363

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Disseminated cutaneous sporotrichosis in an AIDS patient receiving maintenance therapy with fluconazole for previous cryptococcal meningitis. Author(s): Goldani LZ, Aquino VR, Dargel AA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 June; 28(6): 1337-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10451188

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Dosage adjustment of fluconazole during continuous renal replacement therapy (CAVH, CVVH, CAVHD, CVVHD). Author(s): Pittrow L, Penk A. Source: Mycoses. 1999 April; 42(1-2): 17-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10394842

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Dosing guidelines for fluconazole in patients with renal failure. Author(s): Cousin L, Berre ML, Launay-Vacher V, Izzedine H, Deray G. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 November; 18(11): 2227-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551347

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Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Author(s): Pelz RK, Hendrix CW, Swoboda SM, Diener-West M, Merz WG, Hammond J, Lipsett PA. Source: Annals of Surgery. 2001 April; 233(4): 542-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11303137

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Drugs recently released in Belgium. Fluconazole--xamoterol fumarate. Author(s): Harvengt C. Source: Acta Clin Belg. 1990; 45(5): 353-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1980391

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Effect of fluconazole on blood levels of tacrolimus. Author(s): Hairhara Y, Makuuchi M, Kawarasaki H, Takayama T, Kubota K, Ito M, Tanaka H, Yoshino H, Hirata M, Kita Y, Kusaka K, Sano K, Saiura A, Ijichi M, Matsukura A, Watanabe M, Hashizume K, Nakatsuka T. Source: Transplantation Proceedings. 1999 November; 31(7): 2767. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10578284

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Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide. Author(s): Niemi M, Neuvonen M, Juntti-Patinen L, Backman JT, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 2003 July; 74(1): 25-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12844132

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Effect of fluconazole on the pharmacokinetics and pharmacodynamics of oral and rectal bromazepam: an application of electroencephalography as the pharmacodynamic method. Author(s): Ohtani Y, Kotegawa T, Tsutsumi K, Morimoto T, Hirose Y, Nakano S. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 183-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831541

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Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Author(s): Kami M, Machida U, Okuzumi K, Matsumura T, Mori Si S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y. Source: British Journal of Haematology. 2002 April; 117(1): 40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918531

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Effect of prolonged fluconazole treatment on Candida albicans in diffusion chambers implanted into mice. Author(s): Sohnle PG, Hahn BL. Source: Antimicrobial Agents and Chemotherapy. 2002 October; 46(10): 3175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234841

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Effects of fluconazole administration in critically ill patients: analysis of bacterial and fungal resistance. Author(s): Rocco TR, Reinert SE, Simms HH. Source: Archives of Surgery (Chicago, Ill. : 1960). 2000 February; 135(2): 160-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668874

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Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabratainfected p47phox-/- knockout mice. Author(s): Ju JY, Polhamus C, Marr KA, Holland SM, Bennett JE. Source: Antimicrobial Agents and Chemotherapy. 2002 May; 46(5): 1240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959551

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Efficacy of caspofungin in the treatment of esophageal candidiasis resistant to fluconazole. Author(s): Kartsonis N, DiNubile MJ, Bartizal K, Hicks PS, Ryan D, Sable CA. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2002 October 1; 31(2): 183-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394797

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Efficacy of fluconazole and itraconazole in the treatment of oral candidiasis in HIV patients. Author(s): Menon T, Umamaheswari K, Kumarasamy N, Solomon S, Thyagarajan SP. Source: Acta Tropica. 2001 October 22; 80(2): 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600094

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Efficacy, tolerability and development of resistance in HIV-positive patients treated with fluconazole for secondary prevention of oropharyngeal candidiasis: a randomized, double-blind, placebo-controlled trial. Author(s): Pagani JL, Chave JP, Casjka C, Glauser MP, Bille J. Source: The Journal of Antimicrobial Chemotherapy. 2002 August; 50(2): 231-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161404

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Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to 2000: increased susceptibility of Candida species to fluconazole. Author(s): Hsueh PR, Teng LJ, Yang PC, Ho SW, Luh KT. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Winter; 8(4): 311-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12523628

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Emergence of resistance to fluconazole as a cause of failure during treatment of histoplasmosis in patients with acquired immunodeficiency disease syndrome. Author(s): Wheat LJ, Connolly P, Smedema M, Brizendine E, Hafner R; AIDS Clinical Trials Group and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 December 1; 33(11): 1910-3. Epub 2001 October 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11692303

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Enhanced contact activity of fluconazole in association with antioxidants against fluconazole-resistant organisms. Author(s): Simonetti G, Villa A, Simonetti N. Source: The Journal of Antimicrobial Chemotherapy. 2002 August; 50(2): 257-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161408

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Enhanced extracellular production of aspartyl proteinase, a virulence factor, by Candida albicans isolates following growth in subinhibitory concentrations of fluconazole. Author(s): Wu T, Wright K, Hurst SF, Morrison CJ. Source: Antimicrobial Agents and Chemotherapy. 2000 May; 44(5): 1200-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770752

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Enteral fluconazole is well absorbed in critically ill surgical patients. Author(s): Pelz RK, Lipsett PA, Swoboda SM, Merz W, Rinaldi MG, Hendrix CW. Source: Surgery. 2002 May; 131(5): 534-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019407

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Enteral fluconazole population pharmacokinetics in patients in the surgical intensive care unit. Author(s): Rajagopalan P, Pelz RK, Lipsett PA, Swoboda SM, Rinaldi MG, Hendrix CW. Source: Pharmacotherapy. 2003 May; 23(5): 592-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741433

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Evaluation of Etest method for determining fluconazole and voriconazole MICs for 279 clinical isolates of Candida species infrequently isolated from blood. Author(s): Maxwell MJ, Messer SA, Hollis RJ, Boyken L, Tendolkar S, Diekema DJ, Pfaller MA. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1087-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624034

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Evaluation of the Etest and disk diffusion methods for determining susceptibilities of 235 bloodstream isolates of Candida glabrata to fluconazole and voriconazole. Author(s): Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1875-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734220

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Fixed drug eruption due to fluconazole. Author(s): Heikkila H, Timonen K, Stubb S. Source: Journal of the American Academy of Dermatology. 2000 May; 42(5 Pt 2): 883-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10767695

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Fluconazole and itraconazole susceptibility of clinical isolates of Cryptococcus neoformans at a tertiary care centre in India: a need for care. Author(s): Datta K, Jain N, Sethi S, Rattan A, Casadevall A, Banerjee U. Source: The Journal of Antimicrobial Chemotherapy. 2003 October; 52(4): 683-6. Epub 2003 September 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951350

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Fluconazole and itraconazole susceptibility of vaginal yeast isolates from Slovakia. Author(s): Sojakova M, Liptajova D, Borovsky M, Subik J. Source: Mycopathologia. 2004 February; 157(2): 163-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119851

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Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care unit patient. Author(s): Gandhi PJ, Menezes PA, Vu HT, Rivera AL, Ramaswamy K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 December 1; 60(23): 2479-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686224

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Fluconazole for antifungal prophylaxis in chemotherapy-induced neutropenia. Author(s): Preston SL, Briceland LL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 January 15; 52(2): 164-73; Quiz 205-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879543

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Fluconazole improves survival in septic shock: a randomized double-blind prospective study. Author(s): Jacobs S, Price Evans DA, Tariq M, Al Omar NF. Source: Critical Care Medicine. 2003 July; 31(7): 1938-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847386

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Fluconazole in combination with flucytosine in the treatment of fluconazole-resistant Candida infections. Author(s): Girmenia C, Venditti M, Martino P. Source: Diagnostic Microbiology and Infectious Disease. 2003 July; 46(3): 227-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867100

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Fluconazole induced fixed drug eruption: a rare offender. Author(s): Goel A, Jain C. Source: The Journal of Dermatology. 2004 April; 31(4): 345-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15187332

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Fluconazole inhibits pseudohyphal growth in Saccharomyces cerevisiae. Author(s): Kontoyiannis DP. Source: Chemotherapy. 2000 March-April; 46(2): 100-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10671759

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Fluconazole plus amphotericin B combinations are not contraindicated and may add benefit for the treatment of candidemia. Author(s): Odds FC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 May 15; 36(10): 1229-31. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746766

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Fluconazole resistance rate of Candida species from different regions and hospital types in Taiwan. Author(s): Yang YL, Cheng HH, Ho YA, Hsiao CF, Lo HJ. Source: J Microbiol Immunol Infect. 2003 September; 36(3): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582563

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Fluconazole use in burns patients. Author(s): Rayatt S, Wienbren M, Clarke J. Source: Burns : Journal of the International Society for Burn Injuries. 2000 February; 26(1): 109-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10630329

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Fluconazole versus itraconazole for the prevention of fungal infections in haematooncology. Author(s): Huijgens PC, Simoons-Smit AM, van Loenen AC, Prooy E, van Tinteren H, Ossenkoppele GJ, Jonkhoff AR. Source: Journal of Clinical Pathology. 1999 May; 52(5): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10560360

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Fluconazole: optimized antifungal therapy based on pharmacokinetics. Author(s): Silling G. Source: Mycoses. 2002; 45 Suppl 3: 39-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12690970

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Fluconazole: Pfizer asked to lower Africa price. Author(s): James JS. Source: Aids Treat News. 2000 March 17; (339): 5-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870451

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Fluconazole-induced agranulocytosis with eosinophilia. Author(s): Wong-Beringer A, Shriner K. Source: Pharmacotherapy. 2000 April; 20(4): 484-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772380

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Fluconazole-resistant cryptococcal meningitis. Author(s): Momoff N, Parrish A. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 June; 93(6): 444. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916384

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Fluconazole-resistant Cryptococcus neoformans isolated from an immunocompetent patient without prior exposure to fluconazole. Author(s): Orni-Wasserlauf R, Izkhakov E, Siegman-Igra Y, Bash E, Polacheck I, Giladi M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 December; 29(6): 1592-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10585832

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Flucytosine-fluconazole cross-resistance in purine-cytosine permease-deficient Candida lusitaniae clinical isolates: indirect evidence of a fluconazole uptake transporter. Author(s): Noel T, Francois F, Paumard P, Chastin C, Brethes D, Villard J. Source: Antimicrobial Agents and Chemotherapy. 2003 April; 47(4): 1275-84. Erratum In: Antimicrob Agents Chemother. 2003 June; 47(6): 2062. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654658

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Fungicidal activity of fluconazole against Candida albicans in a synthetic vaginasimulative medium. Author(s): Moosa MY, Sobel JD, Elhalis H, Du W, Akins RA. Source: Antimicrobial Agents and Chemotherapy. 2004 January; 48(1): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693534

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G484S amino acid substitution in lanosterol 14-alpha demethylase (ERG11) is related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical isolate. Author(s): Rodero L, Mellado E, Rodriguez AC, Salve A, Guelfand L, Cahn P, CuencaEstrella M, Davel G, Rodriguez-Tudela JL. Source: Antimicrobial Agents and Chemotherapy. 2003 November; 47(11): 3653-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576140

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Ganciclovir/acyclovir and fluconazole prophylaxis after simultaneous kidneypancreas transplantation. Author(s): Stratta RJ. Source: Transplantation Proceedings. 1998 March; 30(2): 262. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9532024

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Gas chromatographic analysis, with electron capture detection, of the antifungal drug fluconazole in microvolumes of human plasma. Author(s): Beijnen JH, Meenhorst PL, van Gijn R, Hazelager WA, Koks CH, Underberg WJ. Source: Journal of Pharmaceutical and Biomedical Analysis. 1991; 9(10-12): 1173-5. Erratum In: J Pharm Biomed Anal 1992 April; 10(4): 315. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1822192

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Gas chromatographic method for the determination of fluconazole, a novel antifungal agent, in human plasma and urine. Author(s): Wood PR, Tarbit MH. Source: Journal of Chromatography. 1986 November 28; 383(1): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3029152

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Genetic dissimilarity of two fluconazole-resistant Candida albicans strains causing meningitis and oral candidiasis in the same AIDS patient. Author(s): Berenguer J, Diaz-Guerra TM, Ruiz-Diez B, Bernaldo de Quiros JC, Rodriguez-Tudela JL, Martinez-Suarez JV. Source: Journal of Clinical Microbiology. 1996 June; 34(6): 1542-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8735114

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Genotypic characterization of sequential Candida albicans isolates from fluconazoletreated neutropenic patients. Author(s): van Belkum A, Melchers W, de Pauw BE, Scherer S, Quint W, Meis JF. Source: The Journal of Infectious Diseases. 1994 May; 169(5): 1062-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8169392

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Glucuronidation of 3'-azido-3'-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Author(s): Trapnell CB, Klecker RW, Jamis-Dow C, Collins JM. Source: Antimicrobial Agents and Chemotherapy. 1998 July; 42(7): 1592-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9660989

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Granulocyte-macrophage colony-stimulating factor and fluconazole enhance anticryptococcal activity of monocytes from AIDS patients. Author(s): Tascini C, Vecchiarelli A, Preziosi R, Francisci D, Bistoni F, Baldelli F. Source: Aids (London, England). 1999 January 14; 13(1): 49-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10207544

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Granulomatous amebic encephalitis in a patient with AIDS: isolation of acanthamoeba sp. Group II from brain tissue and successful treatment with sulfadiazine and fluconazole. Author(s): Seijo Martinez M, Gonzalez-Mediero G, Santiago P, Rodriguez De Lope A, Diz J, Conde C, Visvesvara GS. Source: Journal of Clinical Microbiology. 2000 October; 38(10): 3892-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11015431

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Hazards of inadequate fluconazole dosage to treat deep-seated or systemic Candida albicans infection. Author(s): Flanagan PG, Barnes RA. Source: The Journal of Infection. 1997 November; 35(3): 295-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9459405

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Hepatosplenic candidiasis: successful treatment with fluconazole. Author(s): Kauffman CA, Bradley SF, Ross SC, Weber DR. Source: The American Journal of Medicine. 1991 August; 91(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1867239

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Hepatosplenic candidosis in an immunosuppressed patient responding to fluconazole. Author(s): Torres-Valdivieso MJ, Lopez J, Melero C, Vivanco JL, Cela E, Garcia A, Ruiz Contreras J, Serrano C. Source: Mycoses. 1994 November-December; 37(11-12): 443-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7659134

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Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis. Author(s): Martinez M, Lopez-Ribot JL, Kirkpatrick WR, Bachmann SP, Perea S, Ruesga MT, Patterson TF. Source: The Journal of Antimicrobial Chemotherapy. 2002 March; 49(3): 515-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11864952

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Heteroresistance to fluconazole and voriconazole in Cryptococcus neoformans. Author(s): Mondon P, Petter R, Amalfitano G, Luzzati R, Concia E, Polacheck I, KwonChung KJ. Source: Antimicrobial Agents and Chemotherapy. 1999 August; 43(8): 1856-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10428902

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High dose oral fluconazole for oropharyngeal candidosis in AIDS. Author(s): Ansari AM, Gould IM, Douglas JG. Source: The Journal of Antimicrobial Chemotherapy. 1990 April; 25(4): 720-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2351637

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High-dose fluconazole for treatment of cryptococcal disease in patients with human immunodeficiency virus infection. The California Collaborative Treatment Group. Author(s): Haubrich RH, Haghighat D, Bozzette SA, Tilles J, McCutchan JA. Source: The Journal of Infectious Diseases. 1994 July; 170(1): 238-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8014509

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High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS. Author(s): Menichetti F, Fiorio M, Tosti A, Gatti G, Bruna Pasticci M, Miletich F, Marroni M, Bassetti D, Pauluzzi S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 May; 22(5): 838-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8722942

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High-dose fluconazole therapy in Intensive Care Unit. Author(s): De Bellis P, Bonfiglio M, Gerbi G, Bacigalupo P, Buscaglia G, Guido P, Massobrio B. Source: Minerva Anestesiol. 2003 March; 69(3): 145-52, 153-57. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792583

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High-dose fluconazole therapy in patients with severe fungal infections. Author(s): Voss A, de Pauw BE. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 March; 18(3): 165-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10357048

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High-dose therapy with fluconazole > or = 800 mg day-1. Author(s): Duswald KH, Penk A, Pittrow L. Source: Mycoses. 1997 November; 40(7-8): 267-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9476509

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High-performance liquid chromatographic determination of the antifungal drug fluconazole in plasma and saliva of human immunodeficiency virus-infected patients. Author(s): Koks CH, Rosing H, Meenhorst PL, Bult A, Beijnen JH. Source: Journal of Chromatography. B, Biomedical Applications. 1995 January 20; 663(2): 345-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7735482

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Histoplasmosis in the acquired immunodeficiency syndrome (AIDS): treatment with itraconazole and fluconazole. Author(s): Sharkey-Mathis PK, Velez J, Fetchick R, Graybill JR. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 1993 July; 6(7): 80919. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8389850

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Hospital specificity, region specificity, and fluconazole resistance of Candida albicans bloodstream isolates. Author(s): Pfaller MA, Lockhart SR, Pujol C, Swails-Wenger JA, Messer SA, Edmond MB, Jones RN, Wenzel RP, Soll DR. Source: Journal of Clinical Microbiology. 1998 June; 36(6): 1518-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9620370

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Human carcinogenic risk assessment based on hormonal effects in a carcinogenicity study in rats with the antifungal agent, fluconazole. Author(s): Paulus G, Longeart L, Monro AM. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1994; 14(6): 251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7709362

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Human subcutaneous tissue distribution of fluconazole: comparison of microdialysis and suction blister techniques. Author(s): Sasongko L, Williams KM, Day RO, McLachlan AJ. Source: British Journal of Clinical Pharmacology. 2003 November; 56(5): 551-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651730

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Hypokalaemia in patients with acute myeloid leukaemia after treatment with fluconazole. Author(s): Kidd D, Ranaghan EA, Morris TC. Source: Lancet. 1989 May 6; 1(8645): 1017. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2565490

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Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Author(s): Posteraro B, Sanguinetti M, Sanglard D, La Sorda M, Boccia S, Romano L, Morace G, Fadda G. Source: Molecular Microbiology. 2003 January; 47(2): 357-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519188

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Impact of lysozyme and lactoferrin on oral Candida isolates exposed to polyene antimycotics and fluconazole. Author(s): Anil S, Samaranayake LP. Source: Oral Diseases. 2002 July; 8(4): 199-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12206401

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In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazoleresistant isolates. Author(s): Pfaller MA, Diekema DJ, Messer SA, Hollis RJ, Jones RN. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 1068-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604543

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In vitro activities of voriconazole, posaconazole, and fluconazole against 4,169 clinical isolates of Candida spp. and Cryptococcus neoformans collected during 2001 and 2002 in the ARTEMIS global antifungal surveillance program. Author(s): Pfaller MA, Messer SA, Boyken L, Hollis RJ, Rice C, Tendolkar S, Diekema DJ. Source: Diagnostic Microbiology and Infectious Disease. 2004 March; 48(3): 201-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023430

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In vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine against Aspergillus spp. Author(s): Mosquera J, Sharp A, Moore CB, Warn PA, Denning DW. Source: The Journal of Antimicrobial Chemotherapy. 2002 August; 50(2): 189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161398

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In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592). Author(s): Yildiran ST, Fothergill AW, Sutton DA, Rinaldi MG. Source: Mycoses. 2002 November; 45(9-10): 378-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12421285

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In vitro susceptibility of yeasts for fluconazole and itraconazole. Evaluation of a microdilution test. Author(s): Nenoff P, Oswald U, Haustein UF. Source: Mycoses. 1999; 42(11-12): 629-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10680439

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Influence of fluconazole at subinhibitory concentrations on cell surface hydrophobicity and phagocytosis of Candida albicans. Author(s): Hazen KC, Mandell G, Coleman E, Wu G. Source: Fems Microbiology Letters. 2000 February 1; 183(1): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10650207

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Interaction of all-trans-retinoic acid with fluconazole in acute promyelocytic leukemia. Author(s): Vanier KL, Mattiussi AJ, Johnston DL. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 May; 25(5): 403-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759628

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Intracutaneous distributions of fluconazole, itraconazole, and griseofulvin in Guinea pigs and binding to human stratum corneum. Author(s): Sobue S, Sekiguchi K, Nabeshima T. Source: Antimicrobial Agents and Chemotherapy. 2004 January; 48(1): 216-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693542

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Intravenous and oral itraconazole versus intravenous and oral fluconazole for longterm antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Author(s): Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL, Leitz GJ, Territo MC. Source: Annals of Internal Medicine. 2003 May 6; 138(9): 705-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729424

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In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole. Author(s): Carrillo-Munoz AJ, Quindos G, Tur C, Ruesga MT, Miranda Y, del Valle O, Cossum PA, Wallace TL. Source: The Journal of Antimicrobial Chemotherapy. 1999 September; 44(3): 397-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10511410

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Is there any relationship between fluconazole resistance and some virulence factors in Candida albicans strains? Author(s): Ozkutuk A, Ergon C, Ozdemir S, Yulug N. Source: J Chemother. 2003 December; 15(6): 616-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998091

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Itraconazole and fluconazole and certain rare, serious adverse events. Author(s): Bradbury BD, Jick SS. Source: Pharmacotherapy. 2002 June; 22(6): 697-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12066960

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Itraconazole solution: summary of pharmacokinetic features and review of activity in the treatment of fluconazole-resistant oral candidosis in HIV-infected persons. Author(s): Koks CH, Meenhorst PL, Bult A, Beijnen JH. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 August; 46(2): 195-201. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220961

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Itraconazole versus fluconazole for antifungal prophylaxis. Author(s): Mossad SB. Source: Annals of Internal Medicine. 2004 April 6; 140(7): 580-1; Author Reply 581-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068993

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Itraconazole versus fluconazole for antifungal prophylaxis. Author(s): Powers JH, Higgins KM. Source: Annals of Internal Medicine. 2004 April 6; 140(7): 580; Author Reply 581-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068992

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Itraconazole versus fluconazole for antifungal prophylaxis. Author(s): Karthaus M, Cornely OA, Ullmann AJ. Source: Annals of Internal Medicine. 2004 April 6; 140(7): 579-80; Author Reply 581-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068991

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Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Author(s): Marr KA, Crippa F, Leisenring W, Hoyle M, Boeckh M, Balajee SA, Nichols WG, Musher B, Corey L. Source: Blood. 2004 February 15; 103(4): 1527-33. Epub 2003 October 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525770

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Itraconazole verus fluconazole in neutropenic patients. Author(s): Huijgens PC, Timmers GJ, Simoons-Smit AM, Van Loenen AC. Source: British Journal of Haematology. 2000 January; 108(1): 196. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10712003

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Karyotyping of fluconazole-resistant yeasts with phenotype reported as Candida krusei or Candida inconspicua. Author(s): Essayag SM, Baily GG, Denning DW, Burnie JP. Source: International Journal of Systematic Bacteriology. 1996 January; 46(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8573520

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Kerion due to Trichophyton mentagrophytes: responsiveness to fluconazole versus terbinafine in a child. Author(s): Otberg N, Tietz HJ, Henz BM, Haas N. Source: Acta Dermato-Venereologica. 2001 November-December; 81(6): 444-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11859959

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Ketoconazole and fluconazole drug interactions. Author(s): Baciewicz AM, Baciewicz FA Jr. Source: Archives of Internal Medicine. 1993 September 13; 153(17): 1970-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8357281

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Ketoconazole and fluconazole drug interactions. Author(s): Honig PK, Cantilena LR. Source: Archives of Internal Medicine. 1994 May 9; 154(9): 1038, 1041. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8179450

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Ketoconazole and fluconazole inhibition of the metabolism of cyclosporin A by human liver in vitro. Author(s): Omar G, Whiting PH, Hawksworth GM, Humphrey MJ, Burke MD. Source: Therapeutic Drug Monitoring. 1997 August; 19(4): 436-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263386

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Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole. Author(s): Greenblatt DJ, von Moltke LL, Harmatz JS, Mertzanis P, Graf JA, Durol AL, Counihan M, Roth-Schechter B, Shader RI. Source: Clinical Pharmacology and Therapeutics. 1998 December; 64(6): 661-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9871431

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Lack of a kinetic interaction between fluconazole and mexiletine. Author(s): Ueno K, Yamaguchi R, Tanaka K, Sakaguchi M, Morishima Y, Yamauchi K, Iwai A. Source: European Journal of Clinical Pharmacology. 1996; 50(1-2): 129-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8739823

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Lack of cross-hepatotoxicity between fluconazole and voriconazole. Author(s): Spellberg B, Rieg G, Bayer A, Edwards JE Jr. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 15; 36(8): 1091-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684933

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Lack of effect of fluconazole on the pharmacokinetics of rifampicin in AIDS patients. Author(s): Jaruratanasirikul S, Kleepkaew A. Source: The Journal of Antimicrobial Chemotherapy. 1996 November; 38(5): 877-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8961059

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Large-scale multicentre study of fluconazole in the treatment of hospitalised patients with fungal infections. Multicentre European Study Group. Author(s): Troke PF. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1997 April; 16(4): 287-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9177962

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Laryngeal cryptococcus. Treatment with oral fluconazole. Author(s): Kerschner JE, Ridley MB, Greene JN. Source: Archives of Otolaryngology--Head & Neck Surgery. 1995 October; 121(10): 11935. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7546590

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Levels of fluconazole in normal and diseased nails during and after treatment of onychomycoses in toe-nails with fluconazole 150 mg once weekly. Author(s): Faergemann J, Laufen H. Source: Acta Dermato-Venereologica. 1996 May; 76(3): 219-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8800303

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Levels of fluconazole in serum, stratum corneum, epidermis-dermis (without stratum corneum) and eccrine sweat. Author(s): Faergemann J, Laufen H. Source: Clinical and Experimental Dermatology. 1993 March; 18(2): 102-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8481982

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Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. Author(s): Leenders AC, Reiss P, Portegies P, Clezy K, Hop WC, Hoy J, Borleffs JC, Allworth T, Kauffmann RH, Jones P, Kroon FP, Verbrugh HA, de Marie S. Source: Aids (London, England). 1997 October; 11(12): 1463-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9342068

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Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome. Author(s): Mattiuzzi GN, Estey E, Raad I, Giles F, Cortes J, Shen Y, Kontoyiannis D, Koller C, Munsell M, Beran M, Kantarjian H. Source: Cancer. 2003 January 15; 97(2): 450-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518369

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Liquid/liquid extraction using 96-well plate format in conjunction with hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the analysis of fluconazole in human plasma. Author(s): Eerkes A, Shou WZ, Naidong W. Source: Journal of Pharmaceutical and Biomedical Analysis. 2003 April 1; 31(5): 917-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684104

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Long QT syndrome and torsade de pointes in a patient receiving fluconazole. Author(s): Wassmann S, Nickenig G, Bohm M. Source: Annals of Internal Medicine. 1999 November 16; 131(10): 797. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577320

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Longitudinal melanonychia associated with fluconazole therapy. Author(s): Kar HK. Source: International Journal of Dermatology. 1998 September; 37(9): 719-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9762834

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Long-term observation of a case of cutaneous blastomycosis in Poland treated with fluconazole. Author(s): Chodorowska G, Lecewicz-Torun B. Source: Mycoses. 1996 July-August; 39(7-8): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9009646

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Long-term survival after fluconazole therapy of candidal prosthetic valve endocarditis. Author(s): Czwerwiec FS, Bilsker MS, Kamerman ML, Bisno AL. Source: The American Journal of Medicine. 1993 May; 94(5): 545-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8498400

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Long-term treatment of a breastfeeding mother with fluconazole-resolved nipple pain caused by yeast: a case study. Author(s): Bodley V, Powers D. Source: Journal of Human Lactation : Official Journal of International Lactation Consultant Association. 1997 December; 13(4): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9429366

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Loss of blood pressure control on withdrawal of fluconazole during nifedipine therapy. Author(s): Kremens B, Brendel E, Bald M, Czyborra P, Michel MC. Source: British Journal of Clinical Pharmacology. 1999 June; 47(6): 707-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10438200

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Low levels of antigenic variability in fluconazole-susceptible and -resistant Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Author(s): Lopez-Ribot JL, McAtee RK, Kirkpatrick WR, La Valle R, Patterson TF. Source: Clinical and Diagnostic Laboratory Immunology. 1999 September; 6(5): 665-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10473514

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Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of < or = 100/mm3: demonstration of efficacy in a positive, multicenter trial. Author(s): Singh N, Barnish MJ, Berman S, Bender B, Wagener MM, Rinaldi MG, Yu VL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 December; 23(6): 1282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8953072

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Low-dose fluconazole therapy potentiates the hypoprothrombinemic response of warfarin sodium. Author(s): Crussell-Porter LL, Rindone JP, Ford MA, Jaskar DW. Source: Archives of Internal Medicine. 1993 January 11; 153(1): 102-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8422191

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Lumiracoxib: pharmacokinetic and pharmacodynamic profile when coadministered with fluconazole in healthy subjects. Author(s): Scott G, Yih L, Yeh CM, Milosavljev S, Laurent A, Rordorf C. Source: Journal of Clinical Pharmacology. 2004 February; 44(2): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747429

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Macrophage colony-stimulating factor (M-CSF) induction of enhanced anticryptococcal activity in human monocyte-derived macrophages: synergy with fluconazole for killing. Author(s): Nassar F, Brummer E, Stevens DA. Source: Cellular Immunology. 1995 August; 164(1): 113-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7634342

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Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Author(s): Anaissie EJ, Darouiche RO, Abi-Said D, Uzun O, Mera J, Gentry LO, Williams T, Kontoyiannis DP, Karl CL, Bodey GP. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 November; 23(5): 964-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8922787

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Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients. Author(s): Maebashi K, Niimi M, Kudoh M, Fischer FJ, Makimura K, Niimi K, Piper RJ, Uchida K, Arisawa M, Cannon RD, Yamaguchi H. Source: The Journal of Antimicrobial Chemotherapy. 2001 May; 47(5): 527-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328762

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Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives. Author(s): Devenport MH, Crook D, Wynn V, Lees LJ. Source: British Journal of Clinical Pharmacology. 1989 June; 27(6): 851-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2547410

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Metabolism of rifabutin and its 25-desacetyl metabolite, LM565, by human liver microsomes and recombinant human cytochrome P-450 3A4: relevance to clinical interaction with fluconazole. Author(s): Trapnell CB, Jamis-Dow C, Klecker RW, Collins JM. Source: Antimicrobial Agents and Chemotherapy. 1997 May; 41(5): 924-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9145845

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Methadone and fluconazole: respiratory depression by drug interaction. Author(s): Tarumi Y, Pereira J, Watanabe S. Source: Journal of Pain and Symptom Management. 2002 February; 23(2): 148-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844635

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Molecular aspects of fluconazole resistance development in Candida albicans. Author(s): Franz R, Ruhnke M, Morschhauser J. Source: Mycoses. 1999; 42(7-8): 453-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546486

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Molecular epidemiology of Candida isolates from AIDS patients showing different fluconazole resistance profiles. Author(s): Lischewski A, Ruhnke M, Tennagen I, Schonian G, Morschhauser J, Hacker J. Source: Journal of Clinical Microbiology. 1995 March; 33(3): 769-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7751395

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Molecular heterogeneity of fluconazole-resistant and -susceptible oral Candida albicans isolates within a single geographic locale. Author(s): Dassanayake RS, Ellepola AN, Samaranayake YH, Samaranayak LP. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2002 April; 110(4): 315-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076267

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Molecular karyotyping of multiple yeast species isolated from nine patients with AIDS during prolonged fluconazole therapy. Author(s): Espinel-Ingroff A, Quart A, Steele-Moore L, Metcheva I, Buck GA, Bruzzese VL, Reich D. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1996 March-April; 34(2): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732356

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Molecular mechanisms of fluconazole resistance in Candida dubliniensis isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Author(s): Perea S, Lopez-Ribot JL, Wickes BL, Kirkpatrick WR, Dib OP, Bachmann SP, Keller SM, Martinez M, Patterson TF. Source: Antimicrobial Agents and Chemotherapy. 2002 June; 46(6): 1695-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019078

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Molecular typing and fluconazole susceptibility of urinary Candida glabrata isolates from hospitalized patients. Author(s): Schwab U, Chernomas F, Larcom L, Weems J. Source: Diagnostic Microbiology and Infectious Disease. 1997 September; 29(1): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9350410

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MRI findings and encouraging fluconazole treatment results of intracranial Cladosporium trichoides infection. Author(s): Turker A, Altinors N, Aciduman A, Demiralp O, Uluoglu U. Source: Infection. 1995 January-February; 23(1): 60-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744496

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Mucormycosis in a diabetic child and its treatment with fluconazole: a case report. Author(s): Selcen D, Secmeer G, Aysun S, Kanra G, Onerci M, Gokoz A, Ecevit Z, Ceyhan M, Anlar Y. Source: Turk J Pediatr. 1995 April-June; 37(2): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7597768

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Multicenter comparative evaluation of six commercial systems and the national committee for clinical laboratory standards m27-a broth microdilution method for fluconazole susceptibility testing of Candida species. Author(s): Morace G, Amato G, Bistoni F, Fadda G, Marone P, Montagna MT, Oliveri S, Polonelli L, Rigoli R, Mancuso I, La Face S, Masucci L, Romano L, Napoli C, Tato D, Buscema MG, Belli CM, Piccirillo MM, Conti S, Covan S, Fanti F, Cavanna C, D'Alo F, Pitzurra L. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2953-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149358

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Multicenter evaluation of broth microdilution method for susceptibility testing of Cryptococcus neoformans against fluconazole. Author(s): Sanati H, Messer SA, Pfaller M, Witt M, Larsen R, Espinel-Ingroff A, Ghannoum M. Source: Journal of Clinical Microbiology. 1996 May; 34(5): 1280-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8727919

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Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Author(s): Phillips P, Shafran S, Garber G, Rotstein C, Smaill F, Fong I, Salit I, Miller M, Williams K, Conly JM, Singer J, Ioannou S. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1997 May; 16(5): 337-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9228472

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Multiple malformation syndrome following fluconazole use in pregnancy: report of an additional patient. Author(s): Aleck KA, Bartley DL. Source: American Journal of Medical Genetics. 1997 October 31; 72(3): 253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9332650

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Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Author(s): Franz R, Kelly SL, Lamb DC, Kelly DE, Ruhnke M, Morschhauser J. Source: Antimicrobial Agents and Chemotherapy. 1998 December; 42(12): 3065-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9835492

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Multiple patterns of resistance to fluconazole in Candida glabrata isolates from a patient with oropharyngeal candidiasis receiving head and neck radiation. Author(s): Redding SW, Kirkpatrick WR, Saville S, Coco BJ, White W, Fothergill A, Rinaldi M, Eng T, Patterson TF, Lopez-Ribot J. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 619-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574256

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New indication for oral fluconazole. Author(s): Holdcroft C. Source: The Nurse Practitioner. 1995 January; 20(1): 79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7898795

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New triazole antifungal agents (fluconazole and itraconazole) in the treatment of HIV-related gastrointestinal candidiasis. Author(s): Nathwani D, Green ST, McGuire W, Goldberg DJ, Kennedy DH. Source: Scandinavian Journal of Infectious Diseases. 1989; 21(3): 355-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2547244

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Nosocomial Cryptococcus laurentii fungemia in a bone marrow transplant patient after prophylaxis with ketoconazole successfully treated with oral fluconazole. Author(s): Krcmery V Jr, Kunova A, Mardiak J. Source: Infection. 1997 March-April; 25(2): 130. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9108194

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Nosocomial Torulopsis glabrata fungemia with shock in a pregnant woman successfully treated with high doses of fluconazole and delivery of healthy child. Author(s): Krcmery S, Masar O, Krcmery V Jr. Source: J Chemother. 1995 June; 7(3): 253. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7562024

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Novel fluorescent broth microdilution method for fluconazole susceptibility testing of Candida albicans. Author(s): Liao RS, Rennie RP, Talbot JA. Source: Journal of Clinical Microbiology. 2001 July; 39(7): 2708-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11427602

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Nursery outbreak of neonatal fungal arthritis treated with fluconazole. Author(s): Merchant RH, Sanghvi KP, Sridhar N, Sonigara S, Mehta KP, Joshi NC. Source: Journal of Tropical Pediatrics. 1997 April; 43(2): 106-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9143182

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Ocular fluconazole treatment of Candida parapsilosis endophthalmitis after failed intravitreal amphotericin B. Author(s): Borne MJ, Elliott JH, O'Day DM. Source: Archives of Ophthalmology. 1993 October; 111(10): 1326-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8216010

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Once weekly fluconazole is effective in children in the treatment of tinea capitis: a prospective, multicentre study. Author(s): Gupta AK, Dlova N, Taborda P, Morar N, Taborda V, Lynde CW, Konnikov N, Borges M, Raboobee N, Summerbell RC, Adam P, Hofstader SL, Aboobaker J. Source: The British Journal of Dermatology. 2000 May; 142(5): 965-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10809856

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Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail. Author(s): Drake L, Babel D, Stewart DM, Rich P, Ling MR, Breneman D, Scher RK, Martin AG, Pariser DM, Pariser RJ, Ellis CN, Kang S, Katz HI, McDonald CJ, Muglia J, Savin RC, Webster G, Elewski BE, Leyden JJ, Bucko AD, Tschen EH, Hanifin JM, Morman MR, Shupack JL, Greer DL, et al. Source: Journal of the American Academy of Dermatology. 1998 June; 38(6 Pt 2): S87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631990

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Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail. Author(s): Scher RK, Breneman D, Rich P, Savin RC, Feingold DS, Konnikov N, Shupack JL, Pinnell S, Levine N, Lowe NJ, Aly R, Odom RB, Greer DL, Morman MR, Bucko AD, Tschen EH, Elewski BE, Smith EB. Source: Journal of the American Academy of Dermatology. 1998 June; 38(6 Pt 2): S77-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631989

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Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal subungual onychomycosis of the toenail. Author(s): Ling MR, Swinyer LJ, Jarratt MT, Falo L, Monroe EW, Tharp M, Kalivas J, Weinstein GD, Asarch RG, Drake L, Martin AG, Leyden JJ, Cook J, Pariser DM, Pariser R, Thiers BH, Lebwohl MG, Babel D, Stewart DM, Eaglstein WH, Falanga V, Katz HI, Bergfeld WF, Hanifin JM, Young MR, et al. Source: Journal of the American Academy of Dermatology. 1998 June; 38(6 Pt 2): S95102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631991

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Once-weekly fluconazole in the treatment of onychomycosis: introduction. Author(s): Elewski BE. Source: Journal of the American Academy of Dermatology. 1998 June; 38(6 Pt 2): S73-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631988

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Oral Candida albicans isolates with reduced susceptibility to fluconazole in Swedish HIV-infected patients. Author(s): Chryssanthou E, Torssander J, Petrini B. Source: Scandinavian Journal of Infectious Diseases. 1995; 27(4): 391-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8658076

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Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Author(s): Jacobs LG, Skidmore EA, Freeman K, Lipschultz D, Fox N. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 January; 22(1): 30-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8824962

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Oral fluconazole for Candida urinary tract infection. Author(s): Potasman I, Castin A, Moskovitz B, Srugo I, Nativ O. Source: Urologia Internationalis. 1997; 59(4): 252-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9444745

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Oral fluconazole for vaginal candidiasis. Author(s): Desai PC, Johnson BA. Source: American Family Physician. 1996 September 15; 54(4): 1337-40, 1345-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8816577

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Oral fluconazole in the treatment of pulmonary cryptococcosis in non-AIDS patients. Author(s): Yew WW, Wong PC, Wong CF, Lee J, Chau CH. Source: Drugs Exp Clin Res. 1996; 22(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8839634

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Oral fluconazole therapy for keratomycosis. Author(s): Thakar M. Source: Acta Ophthalmol (Copenh). 1994 December; 72(6): 765-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7747592

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Oral fluconazole treatment of fungating candidiasis in the keratitis, ichthyosis and deafness (KID) syndrome. Author(s): Shiraishi S, Murakami S, Miki Y. Source: The British Journal of Dermatology. 1994 December; 131(6): 904-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7857850

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Oral fluconazole versus amphotericin B bladder irrigation for treatment of candidal funguria. Author(s): Fan-Havard P, O'Donovan C, Smith SM, Oh J, Bamberger M, Eng RH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 October; 21(4): 960-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8645847

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Oral transmission of Candida albicans between partners in HIV-infected couples could contribute to dissemination of fluconazole-resistant isolates. Author(s): Dromer F, Improvisi L, Dupont B, Eliaszewicz M, Pialoux G, Fournier S, Feuillie V. Source: Aids (London, England). 1997 July 15; 11(9): 1095-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9233455

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Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin. The Multicenter Fluconazole Study Group. Author(s): Flynn PM, Cunningham CK, Kerkering T, San Jorge AR, Peters VB, Pitel PA, Harris J, Gilbert G, Castagnaro L, Robinson P. Source: The Journal of Pediatrics. 1995 August; 127(2): 322-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7636666

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Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions. Author(s): Pons V, Greenspan D, Lozada-Nur F, McPhail L, Gallant JE, Tunkel A, Johnson CC, McCarty J, Panzer H, Levenstein M, Barranco A, Green S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 June; 24(6): 1204-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9195083

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Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy. Author(s): Heald AE, Cox GM, Schell WA, Bartlett JA, Perfect JR. Source: Aids (London, England). 1996 March; 10(3): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8882665

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Peritoneal penetration of amphotericin B lipid complex and fluconazole in a pediatric patient with fungal peritonitis. Author(s): Blowey DL, Garg UC, Kearns GL, Warady BA. Source: Adv Perit Dial. 1998; 14: 247-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10649734

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Pharmacodynamics of fluconazole, itraconazole, and amphotericin B against Candida albicans. Author(s): Burgess DS, Hastings RW, Summers KK, Hardin TC, Rinaldi MG. Source: Diagnostic Microbiology and Infectious Disease. 2000 January; 36(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10744363

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Pharmacokinetics and the most suitable dosing regimen of fluconazole in critically ill patients receiving continuous hemodiafiltration. Author(s): Yagasaki K, Gando S, Matsuda N, Kameue T, Ishitani T, Hirano T, Iseki K. Source: Intensive Care Medicine. 2003 October; 29(10): 1844-8. Epub 2003 September 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680113

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Pharmacokinetics of fluconazole in young infants. Author(s): Nahata MC, Tallian KB, Force RW. Source: Eur J Drug Metab Pharmacokinet. 1999 April-June; 24(2): 155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10510743

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Postmortem findings two weeks after oral treatment for metastatic Candida endophthalmitis with fluconazole. Author(s): Ohnishi Y, Tawara A, Murata T, Sakamoto T, Arakawa T, Ishibashi T. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 1999; 213(5): 341-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10516526

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Prevalence and fluconazole susceptibility of Candida species recovered from the oropharynx of healthcare workers (HCWs) and non-HCWs. Author(s): Klein JD, Levin S. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2004 April; 25(4): 352-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15108737

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Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline. Author(s): Dorsey ST, Biblo LA. Source: The American Journal of Emergency Medicine. 2000 March; 18(2): 227-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10750939

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Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial. Author(s): Winston DJ, Pakrasi A, Busuttil RW. Source: Annals of Internal Medicine. 1999 November 16; 131(10): 729-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577295

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Prophylactic fluconazole promotes reepithelialization in full-face carbon dioxide laser skin resurfacing. Author(s): Conn H, Nanda VS. Source: Lasers in Surgery and Medicine. 2000; 26(2): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10685093

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Pulmonary and hepatic toxicity due to nitrofurantoin and fluconazole treatment. Author(s): Linnebur SA, Parnes BL. Source: The Annals of Pharmacotherapy. 2004 April; 38(4): 612-6. Epub 2004 February 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14966256

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Quality control guidelines for National Committee for Clinical Laboratory Standards recommended broth macrodilution testing of amphotericin B, fluconazole, and flucytosine. Author(s): Pfaller MA, Bale M, Buschelman B, Lancaster M, Espinel-Ingroff A, Rex JH, Rinaldi MG, Cooper CR, McGinnis MR. Source: Journal of Clinical Microbiology. 1995 May; 33(5): 1104-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7615713

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Quality control limits for fluconazole disk susceptibility tests on Mueller-Hinton agar with glucose and methylene blue. Author(s): Barry A, Bille J, Brown S, Ellis D, Meis J, Pfaller M, Rennie R, Rinaldi M, Rogers T, Traczewski M. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3410-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843106

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Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients. Author(s): Winston DJ, Busuttil RW. Source: Transplantation. 2002 September 15; 74(5): 688-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352887

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Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation. Author(s): Koh LP, Kurup A, Goh YT, Fook-Chong SM, Tan PH. Source: American Journal of Hematology. 2002 December; 71(4): 260-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12447954

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Rapid identification of fluconazole resistance using Chrom agar Candida. Author(s): Verghese SL, Padmaja P, Sutha P, Mathew T, Johni ES. Source: Indian J Pathol Microbiol. 2001 July; 44(3): 305-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12024918

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Rapid identification of fluconazole resistance using Chromagar Candida. Author(s): Verghese SL, Padmaja P, Sutha P, Mathew T, John ES. Source: Indian J Pathol Microbiol. 2000 July; 43(3): 343-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11218683

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Rates and extents of antifungal activities of amphotericin B, flucytosine, fluconazole, and voriconazole against Candida lusitaniae determined by microdilution, Etest, and time-kill methods. Author(s): Ernst EJ, Yodoi K, Roling EE, Klepser ME. Source: Antimicrobial Agents and Chemotherapy. 2002 February; 46(2): 578-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796383

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Relapse of coccidioidomycosis despite immune reconstitution after fluconazole secondary prophylaxis in a patient with AIDS. Author(s): Mathew G, Smedema M, Wheat LJ, Goldman M. Source: Mycoses. 2003 February; 46(1-2): 42-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588482

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Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole. Author(s): Martinez M, Lopez-Ribot JL, Kirkpatrick WR, Coco BJ, Bachmann SP, Patterson TF. Source: Journal of Clinical Microbiology. 2002 September; 40(9): 3135-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202543

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Resistant mechanisms of Candida albicans to fluconazole. Author(s): Wang W, Li R, Wang D, Li S, Zhu L, Wang X, Wan Z, Zhai W. Source: Chinese Medical Journal. 1999 May; 112(5): 466-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593521

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Reversal of fluconazole resistance in multidrug efflux-resistant fungi by the Dysidea arenaria sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19tetrol 6-acetate. Author(s): Jacob MR, Hossain CF, Mohammed KA, Smillie TJ, Clark AM, Walker LA, Nagle DG. Source: Journal of Natural Products. 2003 December; 66(12): 1618-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695809

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Role of yeasts as nosocomial pathogens & their susceptibility to fluconazole & amphotericin B. Author(s): Prasad KN, Agarwal J, Dixit AK, Tiwari DP, Dhole TN, Ayyagari A. Source: The Indian Journal of Medical Research. 1999 July; 110: 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10709333

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Severe hepatotoxicity after application of desloratadine and fluconazole. Author(s): Schottker B, Dosch A, Kraemer DM. Source: Acta Haematologica. 2003; 110(1): 43-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12975558

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Simvastatin-fluconazole causing rhabdomyolysis. Author(s): Shaukat A, Benekli M, Vladutiu GD, Slack JL, Wetzler M, Baer MR. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1032-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841814

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Single-dose fluconazole versus itraconazole in pityriasis versicolor. Author(s): Partap R, Kaur I, Chakrabarti A, Kumar B. Source: Dermatology (Basel, Switzerland). 2004; 208(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730238

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Stable susceptibility of Candida blood isolates to fluconazole despite increasing use during the past 10 years. Author(s): Chen YC, Chang SC, Luh KT, Hsieh WC. Source: The Journal of Antimicrobial Chemotherapy. 2003 July; 52(1): 71-7. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775680

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Successful treatment of Candida albicans osteomyelitis of the spine with fluconazole and surgical debridement: case report. Author(s): El-Zaatari MM, Hulten K, Fares Y, Baassiri A, Balkis M, Almashhrawi A, ElZaatari FA. Source: J Chemother. 2002 December; 14(6): 627-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12583556

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Successful treatment of fluconazole-resistant oropharyngeal candidiasis by a combination of fluconazole and terbinafine. Author(s): Ghannoum MA, Elewski B. Source: Clinical and Diagnostic Laboratory Immunology. 1999 November; 6(6): 921-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10548586

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Survival following fulminant hepatic failure from fluconazole induced hepatitis. Author(s): Crerar-Gilbert A, Boots R, Fraenkel D, MacDonald GA. Source: Anaesthesia and Intensive Care. 1999 December; 27(6): 650-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631423

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Susceptibilities of Candida species to amphotericin B and fluconazole: the emergence of fluconazole resistance in Candida tropicalis. Author(s): Yang YL, Ho YA, Cheng HH, Ho M, Lo HJ. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2004 January; 25(1): 60-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756222

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Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Author(s): Del Poeta M, Cruz MC, Cardenas ME, Perfect JR, Heitman J. Source: Antimicrobial Agents and Chemotherapy. 2000 March; 44(3): 739-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10681348

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Synergistic antifungal effect of fluconazole and human polymorphonuclear leukocytes on Paracoccidioides brasiliensis: effect of interferon-gamma and granulocyte-macrophage colony-stimulating factor. Author(s): Kurita N, Brummer E, Oarada M, Miyaji M. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2003 April; 41(2): 131-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964845

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Tacrolimus trough level adjustment after administration of fluconazole to kidney recipients. Author(s): Toda F, Tanabe K, Ito S, Shinmura H, Tokumoto T, Ishida H, Toma H. Source: Transplantation Proceedings. 2002 August; 34(5): 1733-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176555

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The effect of fluconazole on the pharmacokinetics of rosuvastatin. Author(s): Cooper KJ, Martin PD, Dane AL, Warwick MJ, Schneck DW, Cantarini MV. Source: European Journal of Clinical Pharmacology. 2002 November; 58(8): 527-31. Epub 2002 October 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451430

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The efficacy of fluconazole 600 mg/day versus itraconazole 600 mg/day as consolidation therapy of cryptococcal meningitis in AIDS patients. Author(s): Mootsikapun P, Chetchotisakd P, Anunnatsiri S, Choksawadphinyo K. Source: J Med Assoc Thai. 2003 April; 86(4): 293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757072

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The genetic basis of fluconazole resistance development in Candida albicans. Author(s): Morschhauser J. Source: Biochimica Et Biophysica Acta. 2002 July 18; 1587(2-3): 240-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084466

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The pfr1 gene from the human pathogenic fungus Paracoccidioides brasiliensis encodes a half-ABC transporter that is transcribed in response to treatment with fluconazole. Author(s): Gray CH, Ines Borges-Walmsley M, Evans GJ, Walmsley AR. Source: Yeast (Chichester, England). 2003 July 30; 20(10): 865-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868056

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The use of fluconazole and itraconazole in the treatment of Candida albicans infections: a review. Author(s): Martin MV. Source: The Journal of Antimicrobial Chemotherapy. 1999 October; 44(4): 429-37. Review. Erratum In: J Antimicrob Chemother 2000 April; 45(4): 555. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588302

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The use of fluconazole to treat superficial fungal infections in children. Author(s): Gupta AK, Cooper EA, Montero-Gei F. Source: Dermatologic Clinics. 2003 July; 21(3): 537-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956206

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Treatment of fluconazole-refractory oropharyngeal candidiasis with itraconazole oral solution in HIV-positive patients. Author(s): Saag MS, Fessel WJ, Kaufman CA, Merrill KW, Ward DJ, Moskovitz BL, Thomas C, Oleka N, Guarnieri JA, Lee J, Brenner-Gati L, Klausner M. Source: Aids Research and Human Retroviruses. 1999 November 1; 15(16): 1413-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10555103

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Treatment of tinea imbricata: a randomized clinical trial using griseofulvin, terbinafine, itraconazole and fluconazole. Author(s): Wingfield AB, Fernandez-Obregon AC, Wignall FS, Greer DL. Source: The British Journal of Dermatology. 2004 January; 150(1): 119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14746625

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Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida. Author(s): Pfaller MA, Diekema DJ; International Fungal Surveillance Participant Group. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2004 March; 10 Suppl 1: 11-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14748799

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Unpredictable cyclosporin--fluconazole interaction in renal transplant recipients. Author(s): Sud K, Singh B, Krishna VS, Thennarasu K, Kohli HS, Jha V, Gupta KL, Sakhuja V. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 July; 14(7): 1698-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435879

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Unusual outcome of disseminated candidiasis treated with fluconazole: a matter of pharmacokinetics? Author(s): Faucher JF, Thiebaut MM, Reynes J, Janbon F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 January; 26(1): 197-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9455541

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Use of antifungal therapy in hospitalized patients. II. Results after the marketing of fluconazole. Author(s): Grasela TH, Pasko MT, Goodwin SD, Walawander CA, Blackwelder N, Bruder-Holt RJ. Source: The Annals of Pharmacotherapy. 1994 February; 28(2): 261-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8173148

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Use of fluconazole in daily practice: still room for improvement. Author(s): Natsch S, Steeghs MH, Hekster YA, Meis JF, van der Meer JW, Kullberg BJ. Source: The Journal of Antimicrobial Chemotherapy. 2001 August; 48(2): 303-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11481307

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Use of fluconazole in newborn infants with systemic candidiasis. Author(s): Caksen H, Kurtoglu S, Ozturk A, Cetin N, Ciftci A. Source: Indian J Pediatr. 2001 August; 68(8): 797-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11563262

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Use of fluconazole in the treatment of candidal endophthalmitis. Author(s): Akler ME, Vellend H, McNeely DM, Walmsley SL, Gold WL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 March; 20(3): 657-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7756492

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Use of fluconazole in the treatment of non-AIDS cryptococcal meningitis. Author(s): Antony SJ, Patel A, Leonard J. Source: Journal of the National Medical Association. 1997 October; 89(10): 694-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9347685

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Use of fluconazole is not associated with a higher incidence of Candida krusei and other non-albicans Candida species. Author(s): Kunova A, Trupl J, Dluholucky S, Galova G, Krcmery V Jr. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 July; 21(1): 226-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7578742

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Use of molecular methods in identification of Candida species and evaluation of fluconazole resistance. Author(s): Cirak MY, Kalkanci A, Kustimur S. Source: Memorias Do Instituto Oswaldo Cruz. 2003 December; 98(8): 1027-32. Epub 2004 March 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15049085

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Use of sargramostim (rh-GM-CSF) as adjunctive treatment of fluconazole-refractory oropharyngeal candidiasis in patients with AIDS: a pilot study. Author(s): Vazquez JA, Hidalgo JA, De Bono S. Source: Hiv Clinical Trials. 2000 November-December; 1(3): 23-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590502

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Variability of plasma fluconazole levels in patients with hematologic malignancy. Author(s): Ellis ME, Spence D, Ernst P, Greer W. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 January; 24(1): 86-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8994774

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Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model. Author(s): Barchiesi F, Najvar LK, Luther MF, Scalise G, Rinaldi MG, Graybill JR. Source: Antimicrobial Agents and Chemotherapy. 1996 May; 40(5): 1317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723495

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Variation in morphotype, karyotype and DNA type of fluconazole resistant Candida albicans from an AIDS patient. Author(s): Takasuka T, Baily GG, Birch M, Anderson MJ, Law D, Denning DW. Source: The Journal of Infection. 1998 January; 36(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9515670

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Variation in random amplified polymorphic DNA (RAPD) profiles specific to fluconazole-resistant and -sensitive strains of Candida albicans. Author(s): Jain P, Khan ZK, Bhattacharya E, Ranade SA. Source: Diagnostic Microbiology and Infectious Disease. 2001 November; 41(3): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750163

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Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location. Author(s): Pfaller MA, Messer SA, Boyken L, Tendolkar S, Hollis RJ, Diekema DJ. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2176-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734273

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Variations in fluconazole susceptibility and DNA subtyping of multiple Candida albicans colonies from patients with AIDS and oral candidiasis suffering one or more episodes of infection. Author(s): Redding SW, Pfaller MA, Messer SA, Smith JA, Prows J, Bradley LL, Fothergill AW, Rinaldi MG. Source: Journal of Clinical Microbiology. 1997 July; 35(7): 1761-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9196188

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Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Author(s): Christmas NJ, Smiddy WE. Source: Ophthalmic Surgery and Lasers. 1996 December; 27(12): 1012-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8976520

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Voriconazole against fluconazole-susceptible and resistant candida isolates: in-vitro efficacy compared with that of itraconazole and ketoconazole. Author(s): Nguyen MH, Yu CY. Source: The Journal of Antimicrobial Chemotherapy. 1998 August; 42(2): 253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9738846

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Voriconazole and fluconazole susceptibility of Candida isolates. Author(s): Pelletier R, Loranger L, Marcotte H, De Carolis E. Source: Journal of Medical Microbiology. 2002 June; 51(6): 479-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12018654

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Vulvovaginitis due to fluconazole resistant Candida albicans following self treatment with non-prescribed triazoles. Author(s): Dorrell L, Edwards A. Source: Sexually Transmitted Infections. 2002 August; 78(4): 308-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12181480

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Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Author(s): Kunze KL, Wienkers LC, Thummel KE, Trager WF. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1996 April; 24(4): 414-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8801056

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Warfarin-fluconazole. II. A metabolically based drug interaction: in vivo studies. Author(s): Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, McDonnell ND, Evans JS, Bauwens JE, Trager WF. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1996 April; 24(4): 422-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8801057

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Warfarin-fluconazole. III. A rational approach to management of a metabolically based drug interaction. Author(s): Kunze KL, Trager WF. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1996 April; 24(4): 429-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8801058

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Weekly fluconazole for preventing mucosal candidiasis in HIV infection. Author(s): Baily G. Source: Annals of Internal Medicine. 1997 December 15; 127(12): 1131. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9412323

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Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS. Author(s): Schuman P, Capps L, Peng G, Vazquez J, el-Sadr W, Goldman AI, Alston B, Besch CL, Vaughn A, Thompson MA, Cobb MN, Kerkering T, Sobel JD. Source: Annals of Internal Medicine. 1997 May 1; 126(9): 689-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9139554

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Weekly fluconazole for the suppression of recurrent thrush in HIV-seropositive patients: impact on the incidence of disseminated cryptococcal infection. Author(s): Newton JA Jr, Tasker SA, Bone WD, Oldfield EC 3rd, Olson PE, Nguyen MT, Wallace MR. Source: Aids (London, England). 1995 November; 9(11): 1286-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8561984

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Weekly fluconazole to prevent candida. Author(s): Gilden D. Source: Gmhc Treat Issues. 1996 June-July; 10(6/7): 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11363636

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Why prior fluconazole use is associated with an increased risk of invasive mold infections in immunosuppressed hosts: an alternative hypothesis. Author(s): Kontoyiannis DP. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 May 1; 34(9): 1281-3; Author Reply 1283. Erratum In: Clin Infect Dis 2002 July 1; 35(1): 110. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11941561

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Widespread cutaneous cryptococcosis occurring in an immunocompromised patient treated with high doses of fluconazole for oro-pharyngeal candidosis. Author(s): Alessandrini F, Allegrini F, Baldari U, Cancellieri C. Source: Acta Dermato-Venereologica. 1997 November; 77(6): 480. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9394988

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Withdrawal of fluconazole suppressive therapy for thrush in patients responding to combination antiviral therapy including protease inhibitors. Author(s): Gripshover BM, Valdez H, Salata RA, Lederman MM. Source: Aids (London, England). 1998 December 24; 12(18): 2513-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9875599

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Y132H substitution in Candida albicans sterol 14alpha-demethylase confers fluconazole resistance by preventing binding to haem. Author(s): Kelly SL, Lamb DC, Kelly DE. Source: Fems Microbiology Letters. 1999 November 15; 180(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10556708

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Yeasts and fluconazole susceptibility in the Philippines. Author(s): Bulmer GS, Marquez ML, Co-Barcelona L, Fromtling RA. Source: Mycopathologia. 1999; 146(3): 117-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10823182

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

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

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

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

Efficacy of melaleuca oral solution for the treatment of fluconazole refractory oral candidiasis in AIDS patients. Author(s): Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, 4160 John R, Suite 2140, Detroit, MI 48201 (USA) Source: Jandourek, A. Vaishampayan, J.K. Vazquez, J.A. AIDS (United Kingdom). (1998). volume 12(9) page 1033-1037.

Additional physician-oriented references include: •

A novel mechanism of fluconazole resistance associated with fluconazole sequestration in Candida albicans isolates from a myelofibrosis patient. Author(s): Teikyo University Institute of Medical Mycology, Hachioji, Tokyo, Japan. [email protected] Source: Maebashi, K Kudoh, M Nishiyama, Y Makimura, K Uchida, K Mori, T Yamaguchi, H Microbiol-Immunol. 2002; 46(5): 317-26 0385-5600

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A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Author(s): Christie Hospital, Manchester. Source: Morgenstern, G R Prentice, A G Prentice, H G Ropner, J E Schey, S A Warnock, D W Br-J-Haematol. 1999 June; 105(4): 901-11 0007-1048

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A synergistic effect of Carica papaya latex sap and fluconazole on Candida albicans growth. Author(s): Laboratoire de Botanique, Cryptogamie et Biologie Cellulaire, Universite de la Mediterranee, Faculte de Pharmacie, Marseille, France. Source: Giordani, R Gachon, C Moulin Traffort, J Regli, P Mycoses. 1997 December; 40(11-12): 429-37 0933-7407

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Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial. Author(s): Department of Haematology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. Source: Timmers, G J Zweegman, S Simoons Smit, A M van Loenen, A C Touw, D Huijgens, P C Bone-Marrow-Transplant. 2000 April; 25(8): 879-84 0268-3369

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Amphotericin B versus fluconazole for controlling fungal infections in neutropenic cancer patients. Author(s): The Nordic Cochrane Centre, Rigshospitalet, Dept. 7112, Blegdamsvej 9, DK2100 Copenhagen O, Denmark. [email protected] Source: Johansen, H K Gotzsche, P C Cochrane-Database-Syst-Revolume 2002; (2): CD000239 1469-493X

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Atovaquone alone or with fluconazole as oral therapy for Indian kala-azar. Author(s): Kala-Azar Medical Research Center, Banaras Hindu University, Varanasi, India. Source: Sundar, S KuMarch, P Makharia, M Goyal, A Rogers, M Gibbs, D Murray, H Clin-Infect-Dis. 1998 July; 27(1): 215-6 1058-4838

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Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Author(s): University of Hacettepe, School of Health Services, Department of Microbiology and Clinical Microbiology, Ankara, Turkey. Source: Ergin, A Arikan, S J-Chemother. 2002 October; 14(5): 465-72 1120-009X

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Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Author(s): Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA. [email protected] Source: Arthington Skaggs, B A Lee Yang, W Ciblak, M A Frade, J P Brandt, M E Hajjeh, R A Harrison, L H Sofair, A N Warnock, D W Antimicrob-Agents-Chemother. 2002 August; 46(8): 2477-81 0066-4804

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Effect of fluconazole on the growth and adhesion of Candida albicans in the presence of antineoplastic agents. Author(s): Department of Microbiology and Biotechnology, Kossuth Lajos University, Debrecen, Hungary. Source: Fekete Forgacs, K Kis, B Nagy, G Lenkey, B J-Basic-Microbiol. 1999; 39(5-6): 30510 0233-111X

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Effect of fluvastatin and pravastatin, HMG-CoA reductase inhibitors, on fluconazole activity against Candida albicans. Author(s): College of Pharmacy, University of Texas at Austin, Department of Pharmacology, University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System San Antonio, USA. Source: Nash, James D Burgess, David S Talbert, Robert L J-Med-Microbiol. 2002 February; 51(2): 105-9 0022-2615

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Effect of iron on fluconazole activity against Candida albicans in presence of human serum or monocyte-derived macrophages. Author(s): Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA. Source: Minn, Y Brummer, E Stevens, D A Mycopathologia. 1997; 138(1): 29-35 0301486X

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Effects of fluconazole on the sterol and carbohydrate composition of four species of Candida. Author(s): Veterans Affairs Medical Center, Iowa City, Iowa. Source: Pfaller, M Riley, J Eur-J-Clin-Microbiol-Infect-Dis. 1992 February; 11(2): 152-6 0934-9723

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Effects of systemic fluconazole therapy on in vitro adhesion of Candida albicans to buccal epithelial cells and changes of the cell surface proteins of the epithelial cells. Author(s): Institute of Dermatology, CAMS & PUMC, Nanjing. Source: Wu, S Guo, N Hou, Y Chin-Med-Sci-J. 1996 March; 11(1): 45-8 1001-9294

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Efflux-mediated resistance to fluconazole could be modulated by sterol homeostasis in Saccharomyces cerevisiae. Author(s): Department of Medical Specialties, Section of Infectious Diseases, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 47, Houston, TX 77030, USA. [email protected]

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Source: Kontoyiannis, D P J-Antimicrob-Chemother. 2000 August; 46(2): 199-203 03057453 •

Enhanced contact activity of fluconazole in association with antioxidants against fluconazole-resistant organisms. Author(s): University of Rome La Sapienza, Institute of Microbiology, Faculty of Pharmacy, Piazzale Aldo Moro 5, 00185 Rome, Italy. Source: Simonetti, G Villa, A Simonetti, N J-Antimicrob-Chemother. 2002 August; 50(2): 257-9 0305-7453

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Evaluation of interaction between fluconazole and an oral contraceptive in healthy women. Author(s): Clinical Pharmacology, Pfizer Global Research and Development, Pfizer, Inc., Groton, Connecticut 06340, USA. [email protected] Source: Hilbert, J Messig, M Kuye, O Friedman, H Obstet-Gynecol. 2001 August; 98(2): 218-23 0029-7844

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Fungispecificity of fluconazole against Candida albicans. Author(s): Department of Surgery, Children's Hospital Medical Center, Boston, MA 02115. Source: Liss, R H Letourneau, R J Mycopathologia. 1989 December; 108(3): 173-8 0301486X

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In vitro activity of fluconazole on Candida albicans. Author(s): Department of Preventive Medicine and Public Health, Faculty of Medicine, University of the Basque Country, Vitoria, Spain. Source: Abecia, L C Arevalo, J M Lopez, M J Microbiologia. 1996 December; 12(4): 613-20 0213-4101

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In vitro susceptibility of yeasts for fluconazole and itraconazole. Evaluation of a microdilution test. Author(s): Department of Dermatology, University of Leipzig, Germany. Source: Nenoff, P Oswald, U Haustein, U F Mycoses. 1999; 42(11-12): 629-39 0933-7407

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Intraocular hemorrhages due to warfarin fluconazole drug interaction in a patient with presumed Candida endophthalmitis. Author(s): University of New Mexico Health Sciences Center, 2211 Lomas Blvd NE, Albuquerque, NM 87131-5341, USA. [email protected] Source: Mootha, V Vinod Schluter, Mark L Das, Arup Arch-Ophthalmol. 2002 January; 120(1): 94-5 0003-9950

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In-vitro activity of D0870, a new triazole antifungal drug, in comparison with fluconazole and itraconazole against Aspergillus fumigatus and Candida krusei. Author(s): Krebs's Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, The University of Sheffield, UK. Source: Venkateswarlu, K Denning, D W Kelly, S L J-Antimicrob-Chemother. 1997 June; 39(6): 731-6 0305-7453

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Mechanism of fluconazole resistance in Candida krusei. Author(s): St. John's Cardiovascular Research Center, Division of Infectious Diseases, Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA. Source: Orozco, A S Higginbotham, L M Hitchcock, C A Parkinson, T Falconer, D Ibrahim, A S Ghannoum, M A Filler, S G Antimicrob-Agents-Chemother. 1998 October; 42(10): 2645-9 0066-4804

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Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients. Author(s): Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan. [email protected] Source: Maebashi, K Niimi, M Kudoh, M Fischer, F J Makimura, K Niimi, K Piper, R J Uchida, K Arisawa, M Cannon, R D Yamaguchi, H J-Antimicrob-Chemother. 2001 May; 47(5): 527-36 0305-7453

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Modulation of fluconazole sensitivity by the interaction of mitochondria and erg3p in Saccharomyces cerevisiae. Author(s): The University of Texas M. D. Anderson Cancer Center, Section of Infectious Diseases, 1515 Holcombe Boulevard, Box 47, Houston, TX 77030, USA. [email protected] Source: Kontoyiannis, D P J-Antimicrob-Chemother. 2000 August; 46(2): 191-7 0305-7453

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Optimizing voriconazole susceptibility testing of Candida: effects of incubation time, endpoint rule, species of Candida, and level of fluconazole susceptibility. Author(s): Division of Infectious Diseases, Department of Internal Medicine, Center for the Study of Emerging and Reemerging Pathogens, University of Texas Medical School, Houston, Texas 77030, USA. Source: Lozano Chiu, M Arikan, S Paetznick, V L Anaissie, E J Rex, J H J-Clin-Microbiol. 1999 September; 37(9): 2755-9 0095-1137

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Quantitation of Candida albicans ergosterol content improves the correlation between in vitro antifungal susceptibility test results and in vivo outcome after fluconazole treatment in a murine model of invasive candidiasis. Author(s): Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. Source: Arthington Skaggs, B A Warnock, D W Morrison, C J Antimicrob-AgentsChemother. 2000 August; 44(8): 2081-5 0066-4804

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Quantitation of ergosterol content: novel method for determination of fluconazole susceptibility of Candida albicans. Author(s): Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. Source: Arthington Skaggs, B A Jradi, H Desai, T Morrison, C J J-Clin-Microbiol. 1999 October; 37(10): 3332-7 0095-1137

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Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Author(s): Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. [email protected] Source: Marr, K A Lyons, C N Rustad, T R Bowden, R A White, T C Rustad, T Antimicrob-Agents-Chemother. 1998 October; 42(10): 2584-9 0066-4804

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Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol. Author(s): Department of Clinical Pharmacology, Royal North Shore Hospital, Sydney, Australia. Source: Gross, A S McLachlan, A J Minns, I Beal, J B Tett, S E Br-J-Clin-Pharmacol. 2001 June; 51(6): 547-55 0306-5251

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Testing susceptibility of Candida species to fluconazole and itraconazole using the microdilution assay. Author(s): Mycology Unit, Robert Koch Institute, Berlin, Germany. Source: Seibold, M Werner, E Mycoses. 1995 Nov-December; 38(11-12): 443-8 0933-7407

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The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity. Author(s): Institute of Biological Sciences, University of Wales Aberystwyth, Aberystwyth, Wales, SY23 3DA, United Kingdom. [email protected] Source: Kelly, S L Lamb, D C Loeffler, J Einsele, H Kelly, D E Biochem-Biophys-ResCommun. 1999 August 19; 262(1): 174-9 0006-291X

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A novel mechanism of fluconazole resistance associated with fluconazole sequestration in Candida albicans isolates from a myelofibrosis patient. Author(s): Maebashi K, Kudoh M, Nishiyama Y, Makimura K, Uchida K, Mori T, Yamaguchi H. Source: Microbiology and Immunology. 2002; 46(5): 317-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139391

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A novel method for studying ergosterol biosynthesis by a cell-free preparation of Aspergillus fumigatus and its inhibition by azole antifungal agents. Author(s): Ballard SA, Ellis SW, Kelly SL, Troke PF. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1990; 28(4): 335-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2176688

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A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. Author(s): Bozzette SA, Larsen RA, Chiu J, Leal MA, Jacobsen J, Rothman P, Robinson P, Gilbert G, McCutchan JA, Tilles J, et al. Source: The New England Journal of Medicine. 1991 February 28; 324(9): 580-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1992319

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A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Author(s): Morgenstern GR, Prentice AG, Prentice HG, Ropner JE, Schey SA, Warnock DW. Source: British Journal of Haematology. 1999 June; 105(4): 901-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10554799

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Antifungal activity of fluconazole in combination with lovastatin and their effects on gene expression in the ergosterol and prenylation pathways in Candida albicans. Author(s): Song JL, Lyons CN, Holleman S, Oliver BG, White TC. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2003 October; 41(5): 417-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653518

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Antifungal activity of Mahonia aquifolium extract and its major protoberberine alkaloids. Author(s): Vollekova A, Kost'alova D, Kettmann V, Toth J. Source: Phytotherapy Research : Ptr. 2003 August; 17(7): 834-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916091

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Antifungal activity of volatile constituents of Eugenia dysenterica leaf oil. Author(s): Costa TR, Fernandes OF, Santos SC, Oliveira CM, Liao LM, Ferri PH, Paula JR, Ferreira HD, Sales BH, Silva M do R. Source: Journal of Ethnopharmacology. 2000 September; 72(1-2): 111-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10967461

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Anxiety and HIV infection. Author(s): Elliott A. Source: Step Perspect. 1998 Winter; 98(1): 11-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11365209

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Bioadhesive, collagen-modified liposomes: molecular and cellular level studies on the kinetics of drug release and on binding to cell monolayers. Author(s): Yerushalmi N, Margalit R.

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Source: Biochimica Et Biophysica Acta. 1994 January 3; 1189(1): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8305454 •

Biochemical basis for the activity and selectivity of oral antifungal drugs. Author(s): Vanden Bossche H, Marichal P, Gorrens J, Coene MC. Source: Br J Clin Pract Suppl. 1990 September; 71: 41-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2091733

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Candiduria in hospitalized patients: a review. Author(s): Nucci M. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2000 August; 4(4): 168-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11008220

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Characteristic biological effects of itraconazole on L929 fibroblasts and their cell membrane. Author(s): Abe S, Ochi H, Takahashi Y, Ishijima SA, Osumi M, Yamaguchi H. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2000 March; 6(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810529

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Characterization of an azole-resistant Candida glabrata isolate. Author(s): vanden Bossche H, Marichal P, Odds FC, Le Jeune L, Coene MC. Source: Antimicrobial Agents and Chemotherapy. 1992 December; 36(12): 2602-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1482129

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Characterization of Saccharomyces cerevisiae CYP61, sterol delta22-desaturase, and inhibition by azole antifungal agents. Author(s): Kelly SL, Lamb DC, Baldwin BC, Corran AJ, Kelly DE. Source: The Journal of Biological Chemistry. 1997 April 11; 272(15): 9986-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9092539

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Clinical microbiological case: fever and headache in a heavy consumer of eucalyptus extract. Author(s): Tascini C, Ferranti S, Gemignani G, Messina F, Menichetti F. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 July; 8(7): 437, 445-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12199856

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Clinical relevance of mechanisms of antifungal drug resistance in yeasts. Author(s): Sanglard D.

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Source: Enfermedades Infecciosas Y Microbiologia Clinica. 2002 November; 20(9): 462-9; Quiz 470, 479. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425880 •

Coccidioidomycosis. Author(s): Powderly WG. Source: J Int Assoc Physicians Aids Care. 1997 March; 3(3): 38-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11364125

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Comparison of D0870, a new triazole antifungal agent, to fluconazole for inhibition of Candida albicans cytochrome P-450 by using in vitro assays. Author(s): Venkateswarlu K, Denning DW, Manning NJ, Kelly SL. Source: Antimicrobial Agents and Chemotherapy. 1996 June; 40(6): 1382-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8726005

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Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Author(s): Ergin A, Arikan S. Source: J Chemother. 2002 October; 14(5): 465-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462426

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Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Author(s): Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, Harrison LH, Sofair AN, Warnock DW; Candidemia Active Surveillance Group. Source: Antimicrobial Agents and Chemotherapy. 2002 August; 46(8): 2477-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12121921

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Diabetes insipidus in a patient with a highly malignant B-cell lymphoma and stomatitis. Author(s): Breidert M, Schimmelpfennig C, Kittner T, Helwig A, Ehninger G. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2000; 108(1): 54-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10768833

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Disseminated cryptococcosis in an AIDS patient caused by a canavanine-resistant strain of Cryptococcus neoformans var. grubii. Author(s): Khan ZU, Al-Anezi AA, Chandy R, Xu J.

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Source: Journal of Medical Microbiology. 2003 March; 52(Pt 3): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621094 •

Drug interactions with itraconazole, fluconazole, and terbinafine and their management. Author(s): Gupta AK, Katz HI, Shear NH. Source: Journal of the American Academy of Dermatology. 1999 August; 41(2 Pt 1): 23749. Review. Erratum In: J Am Acad Dermatol 2000 January; 42(1 Pt 1): 148. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10426895

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Drug susceptibilities of yeast cells are affected by membrane lipid composition. Author(s): Mukhopadhyay K, Kohli A, Prasad R. Source: Antimicrobial Agents and Chemotherapy. 2002 December; 46(12): 3695-705. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435664

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Effect of commercial ethanol propolis extract on the in vitro growth of Candida albicans collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis. Author(s): Martins RS, Pereira ES Jr, Lima SM, Senna MI, Mesquita RA, Santos VR. Source: J Oral Sci. 2002 March; 44(1): 41-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058869

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Effect of fluconazole on the growth and adhesion of Candida albicans in the presence of antineoplastic agents. Author(s): Fekete-Forgacs K, Kis B, Nagy G, Lenkey B. Source: Journal of Basic Microbiology. 1999; 39(5-6): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10629971

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Effects of fluconazole on the sterol and carbohydrate composition of four species of Candida. Author(s): Pfaller M, Riley J. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1992 February; 11(2): 1526. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1396728

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Effects of three azole derivatives on the lipids of different strains of Cryptococcus neoformans. Author(s): Franzot SP, Hamdan JS. Source: Mycoses. 1995 May-June; 38(5-6): 183-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8531929

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Efficacy of alcohol-based and alcohol-free melaleuca oral solution for the treatment of fluconazole-refractory oropharyngeal candidiasis in patients with AIDS. Author(s): Vazquez JA, Zawawi AA. Source: Hiv Clinical Trials. 2002 September-October; 3(5): 379-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407487

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Efflux-mediated resistance to fluconazole could be modulated by sterol homeostasis in Saccharomyces cerevisiae. Author(s): Kontoyiannis DP. Source: The Journal of Antimicrobial Chemotherapy. 2000 August; 46(2): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933641

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Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Author(s): Onyewu C, Blankenship JR, Del Poeta M, Heitman J. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 956-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604527

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European experience with oral solution and intravenous itraconazole. Author(s): Potter M. Source: Oncology (Huntingt). 2001 November; 15(11 Suppl 9): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757848

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Evaluation of differential gene expression in fluconazole-susceptible and -resistant isolates of Candida albicans by cDNA microarray analysis. Author(s): Rogers PD, Barker KS. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3412-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384344

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Genetically recombinant antibodies: new therapeutics against candidiasis. Author(s): Burnie J, Matthews R. Source: Expert Opinion on Biological Therapy. 2004 February; 4(2): 233-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998780

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Hypothesis on the mechanism of resistance to fluconazole in Histoplasma capsulatum. Author(s): Wheat J, Marichal P, Vanden Bossche H, Le Monte A, Connolly P. Source: Antimicrobial Agents and Chemotherapy. 1997 February; 41(2): 410-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9021199

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In vitro activity of fluconazole on Candida albicans. Author(s): Abecia LC, Arevalo JM, Lopez MJ.

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Source: Microbiologia. 1996 December; 12(4): 613-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9018696 •

In-vitro activity of D0870, a new triazole antifungal drug, in comparison with fluconazole and itraconazole against Aspergillus fumigatus and Candida krusei. Author(s): Venkateswarlu K, Denning DW, Kelly SL. Source: The Journal of Antimicrobial Chemotherapy. 1997 June; 39(6): 731-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9222042

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Mechanism of fluconazole resistance in Candida krusei. Author(s): Orozco AS, Higginbotham LM, Hitchcock CA, Parkinson T, Falconer D, Ibrahim AS, Ghannoum MA, Filler SG. Source: Antimicrobial Agents and Chemotherapy. 1998 October; 42(10): 2645-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9756770

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Modulation of fluconazole sensitivity by the interaction of mitochondria and erg3p in Saccharomyces cerevisiae. Author(s): Kontoyiannis DP. Source: The Journal of Antimicrobial Chemotherapy. 2000 August; 46(2): 191-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933640

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Proliferation of intracellular structure corresponding to reduced affinity of fluconazole for cytochrome P-450 in two low-susceptibility strains of Candida albicans isolated from a Japanese AIDS patient. Author(s): Maebashi K, Kudoh M, Nishiyama Y, Makimura K, Kamai Y, Uchida K, Yamaguchi H. Source: Microbiology and Immunology. 2003; 47(2): 117-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680714

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Quantitation of Candida albicans ergosterol content improves the correlation between in vitro antifungal susceptibility test results and in vivo outcome after fluconazole treatment in a murine model of invasive candidiasis. Author(s): Arthington-Skaggs BA, Warnock DW, Morrison CJ. Source: Antimicrobial Agents and Chemotherapy. 2000 August; 44(8): 2081-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898679

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Quantitation of ergosterol content: novel method for determination of fluconazole susceptibility of Candida albicans. Author(s): Arthington-Skaggs BA, Jradi H, Desai T, Morrison CJ. Source: Journal of Clinical Microbiology. 1999 October; 37(10): 3332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10488201

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Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Author(s): Marr KA, Lyons CN, Rustad TR, Bowden RA, White TC, Rustad T. Source: Antimicrobial Agents and Chemotherapy. 1998 October; 42(10): 2584-9. Erratum In: Antimicrob Agents Chemother 1999 February; 43(2): 438. Rustad T[corrected to Rustad Tr]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9756759

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Resistance to fluconazole in Candida albicans from AIDS patients correlated with reduced intracellular accumulation of drug. Author(s): Venkateswarlu K, Denning DW, Manning NJ, Kelly SL. Source: Fems Microbiology Letters. 1995 September 15; 131(3): 337-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7557345

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Stability of paclitaxel and fluconazole during simulated Y-site administration. Author(s): Burm JP, Choi JS, Jhee SS, Chin A, Ulrich RW, Gill MA. Source: Am J Hosp Pharm. 1994 November 1; 51(21): 2704-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7856586

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Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole. Author(s): Ghannoum MA, Spellberg BJ, Ibrahim AS, Ritchie JA, Currie B, Spitzer ED, Edwards JE Jr, Casadevall A. Source: Antimicrobial Agents and Chemotherapy. 1994 September; 38(9): 2029-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7811014

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The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity. Author(s): Kelly SL, Lamb DC, Loeffler J, Einsele H, Kelly DE. Source: Biochemical and Biophysical Research Communications. 1999 August 19; 262(1): 174-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448088

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 fluconazole; 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 Chronic Candidiasis Source: Healthnotes, Inc.; www.healthnotes.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Nail Disorders Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Antifungal Agents Source: Healthnotes, Inc.; www.healthnotes.com Fluconazole Source: Healthnotes, Inc.; www.healthnotes.com Tea Tree Alternative names: Melaleuca alternifolia Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the

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MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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

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

Role of the efflux pumps CaMDR1, CDR1 and CDR2 in the fluconazole susceptibility of primary adhered Candida albicans by Mateus Rugeles, Carolina, PhD from Georgia State University, 2003, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3110461

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

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CHAPTER 5. PATENTS ON FLUCONAZOLE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “fluconazole” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on fluconazole, we have not necessarily excluded nonmedical patents in this bibliography.

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

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

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

Antibiotic cocktail and method of use Inventor(s): Adoma; Chigoke (Katy, TX), Brockbank; Kelvin G.M. (Marietta, GA), Dawson; Patti E. (Marietta, GA), Goldstein; Steven (Atlanta, GA), Sheldon; Judith K. (Smyrna, GA) Assignee(s): Cryolife, Inc. (Kennesaw, GA) Patent Number: 5,741,782 Date filed: March 29, 1996 Abstract: An antibiotic cocktail for sterilizing tissue comprising amphotericin B and fluconazole as antifungal agents and a plurality of antibacterial agents. The agents are present in amounts effective to substantially inhibit fungal and bacterial growth while substantially maintaining the viability of the tissue. Also, a method of sterilizing a tissue comprising contacting the tissue with the antibiotic cocktails of the invention at a temperature and for a period of time effective to substantially inhibit fungal and bacterial growth while substantially maintaining the viability of the tissue. Excerpt(s): This invention relates to a method of decontaminating tissues, such as heart valves, for transplantation while maintaining the viability of the tissue. The invention also relates to an antibiotic cocktail for use in the method. The clinical performance of heart valve allografts has been correlated with the viability of the valve leaflet fibroblasts at transplantation. See, O'Brien et al., J. Card. Surg., 2 (Suppl), 153-167 (1987) and Stark, J. Thoracic Cardiovasc. Surg., 97, 1-9 (1989). Accordingly, the highest viability standards must be maintained throughout the entire processing procedure which includes procurement, transportation, decontamination, freezing, storage, thawing and transplantation. With respect to the decontamination step, antibiotic cocktails for microbial decontamination of tissue are known. In particular, several antibiotic cocktails are known which contain a plurality of antibacterial agents and a single antifungal agent (amphotericin B or, occasionally, nystatin). See, e.g., Watts et al., Ann. Thorac. Surg., 21, 230-36 (1976); Strickett et al., Pathology, 15, 457-62 (1983); Armiger et al., Pathology, 15, 67-73 (1983); Kirklin and Barratt-Boyes, Cardiac Surgery, 421-22 (1986); Heacox et al., in Cardiac Valve Allografts 1962-1987, 37-42 (Yankah et al. eds. 1988); Angell et al., J. Thorac. Cardiovasc. Surg., 98, 48-56 (1989); Lange and Hopkins, in Cardiac Reconstruction With Allograft Heart Valves, 37-63 (Hopkins ed. 1989); U.S. Pat. No. 4,890,457; U.S. Pat. No. 4,695,536; and PCT application WO 92/12632. Web site: http://www.delphion.com/details?pn=US05741782__

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Antifungal composition Inventor(s): Meingassner; Josef Gottfried (Perchtoldsdorf, AT), Ryder; Neil Stewart (Vienna, AT) Assignee(s): Novartis AG (Basel, CH) Patent Number: 5,985,906 Date filed: November 12, 1997 Abstract: Use of a combination of the squalene epoxidase inhibitor terbinafine and an azole 14-alpha-methyldemethylase inhibitor (fluconazole or itraconazole) in mycotic

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infections caused by azole-resistant fungal strains, and corresponding pharmaceutical compositions, process and method. Excerpt(s): The present invention relates to the treatment of human mycotic infections. It concerns antifungal compositions for use in the treatment of mycotic infections caused by azole resistant yeast strains, comprising terbinafine with an azole 14.alpha.methyldemethylase inhibitor such as the azole fluconazole and/or itraconazole. Although they are often present as benign commensal organisms in the digestive tract of healthy individuals, fungi, particularly Candida species produce a broad range of serious illnesses in compromised hosts. Such infections are clearly on the rise. Oropharyngeal candidiasis is the most common fungal infection in patients with human immunodeficiency virus (HIV) infection. With the introduction of azole antifungal agents that are bioavailable after oral administration, the approach to the treatment of serious Candida infections is possible. Ketoconazole, the first of there agents to become available, was quickly found to be efficacious in the setting of chronic mucocutaneous candidiasis. However, not long after the introduction of this agent, clinical failure in association with elevated minimum inhibitory concentrations (MICs) of ketoconazole that developed during prolonged therapy were reported. This problem achieved prominence with the subsequent introduction of fluconazole. Fluconazole, a watersoluble triazole with greater than 90% bioavailability after oral administration, is used extensively to treat a wide range of Candida infections. In particular, it is widely used as therapy for oropharyngeal candidiasis in patients with advanced HIV infection and AIDS. Although oropharyngeal candidiasis usually responds readily to fluconazole, it is difficult to completely eradicate the infection and relapse often occurs within several months following the completion of therapy. For this reason, many AIDS patients receive fluconazole either continuously on intermittently over long periods of time. To a greater extent than with other azoles, resistance to fluconazole has developed and is becoming a significant clinical problem, as attested by isolation from, in particular, AIDS patients of numerous Candida strains showing resistance (see e.g. D. Law et al., J. Antimicrob. Chemother. 34 [1994] 659-668). Web site: http://www.delphion.com/details?pn=US05985906__ •

Azole compounds as therapeutic agents for fungal infections Inventor(s): Arora; Jasbir Singh (New Delhi, IN), Arora; Sudershan K. (Gurgaon, IN), Rattan; Ashok (New Delhi, IN), Verma; Ashwani Kumar (New Delhi, IN) Assignee(s): Ranbaxy Laboratories Limited (New Delhi, IN) Patent Number: 6,670,363 Date filed: May 22, 2000 Abstract: The present invention relates to the derivatives of specially substituted azole compounds which have improved antifungal activity as compared to known compounds such as fluconazole and itraconazole and the processes for the preparation thereof. This invention also relates to pharmaceutical compositions containing the compounds of the present invention and their use in treating and/or preventing fungal infections in mammals, preferably humans. Excerpt(s): Life-threatening, systemic fungal infections continue to be a significant problem in health care today. In particular, patients who become "immunocompromised: as a result of diabetes, cancer, prolonged steroid therapy, organ transplantation antirejection therapy, the acquired immune deficiency syndrome (AIDS)

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or other physiologically or immunologically compromising syndromes, are especially susceptible to opportunistic fungal infections. Most of these infections are caused by opportunistic pathogens, like species of Candida and Aspergillus and Cryptococcus neoformans. During the last 20 years, the incidence of sepsis fungal infection caused by candida species has increased significantly in debilitated and immuno-compromised patients. In addition, the more aggressive and frequently used broad spectrum antibiotic, antineoplastic and immunosuppressive chemotherapies have also augmented fungal infections. Cryptococcosis is a leading cause of morbidity among AIDS patients. The incidence of life threatening cryptococcal infection among these patients have been estimated to vary from 10 to 30%. During initial therapy, 10 to 20% of these patients die and 30 to 60% patients succumb within a year. Amphoteracin B has changed disseminated cryptococcosis from uniformly fatal infection to curable infection but since Amphoteracin B penetrates the central nervous system poorly, interventricular AID injection may have to be administered for successful management of severe cases of patients with cryptococcal meningitis. Invasive aspergillosis has also become a leading cause of death, mainly among patients suffering from acute leukaemia or after allogenic bone marrow transfusion and after cytotoxic treatment of these conditions. It also occurs in patients with condition such as AIDS and chronic granulomatous disease. At present, only Amphoteracin B and itraconazole are available for treatment of aspergillosis. Inspite of their activity in-vitro, the effect of these drugs in-vivo against Aspergillus fumigatus remains low and as a consequence mortality from invasive aspergillosis remains high. Web site: http://www.delphion.com/details?pn=US06670363__ •

Catalyzed enantiomeric selection of 1,2-diols and their cyclization to produce oxiranes Inventor(s): Blacker; Andrew John (Leeds, GB), Brewster; Andrew George (Macclesfield, GB), Copeland; Robert Jeffrey (Macclesfield, GB), Holt; Robert Antony (Northallerton, GB) Assignee(s): Mochida Pharmaceuticals Co., Ltd. (Tokyo, JP), Zeneca Limited (London, GB) Patent Number: 5,854,062 Date filed: December 11, 1995 Abstract: Method of preparing an optically active compound of formula, wherein R and R.sup.1 are independently alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, cycloalkyl, aryl, aralkyl, a heterocyclic group or a C.sub.1 -C.sub.4 alkyl-heterocycle, each being optionally substituted, procided that R and R.sup.1 are not identical and * is an optically active chiral center, from the corresponding racemic ester or diol by treating with a hydrolase enzyme. In particular, racemic 2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1yl)propan-1,2 diol, an intermediate in fluconazole synthesis, is resolved using porcine pancreatic lipase or lipase from Chromobacterium viscosum. Excerpt(s): This application claims benefit of international application PCT/GB94/00793, filed Apr. 15, 1994. This invention relates to a method of chiral resolution of tertiary alcohols and to novel compounds useful in the method. Certain tertiary alcohols are useful compounds in pharmaceutical and agrochemical outlets, for example, the compounds disclosed in GB 1529818, EP-B-15756, EP-B-44605, EP-B-61835, EP-B-131684, EP-A-47594, GB 2064520 and EPA-472392. These compounds usually have an optically active chiral centre and resolution of the compounds can lead to benefits for example, greater activity or lower toxicity with one of the optically active isomers.

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Web site: http://www.delphion.com/details?pn=US05854062__ •

Diaryl substituted thiazoles useful in the treatment of fungal infections Inventor(s): Macina; Orest Taras (Pittsburgh, PA), Riviello; Christopher Mark (Old Forge, PA), Sircar; Ila (Clarks Summit, PA), Sircar; Jagadish Chandra (Clarks Summit, PA), Yu; Dingwei Tim (Easton, PA) Assignee(s): none reported Patent Number: 6,156,776 Date filed: March 25, 1999 Abstract: Disclosed is a novel class of thiazole, thiadiazole, and oxadiazole compounds which are substituted at their nuclear carbons by aromatic moieties. These compounds exhibit antifungal activity against a variety of fungi including strains which have proven to be resistant to treatment with known antifungal agents such as Fluconazole. Excerpt(s): This invention relates to a novel class of substituted azoles and, more specifically, diaryl substituted thiazoles, diaryl substituted thiadiazoles and diaryl substituted oxadiazoles, compounds which are useful in the treatment of fungal infections in mammals including humans. These compounds are active against a broad spectrum of fungi such as Candida albicans, Candida parpsilosis, Candida tropicalis, Candida Krusei, Cryptococcus neoformans, Aspergillus fumigatus and Torulopsis glabrata. Moreover, compounds within this series are also active against Fluconazole resistant strains and isolates. Opportunistic fungal infections are responsible for increased morbidity and mortality among patients suffering from AIDS and other immunocompromised diseases including infections resulting from neutropenia, cancer chemotherapy and organ transplantation (Annals N.Y. Acad. Sc., 544:1-3). Moreover, until recently, the treatment of deep seated fungal infections has lagged behind the treatment of bacterial infections and only a few systemic agents are available for combatting these invasive pathogens. Web site: http://www.delphion.com/details?pn=US06156776__

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Preparation of fluconazole and pharmaceutically acceptable salts thereof Inventor(s): Chen; Lie-Rong (Taipei, TW), Liu; Ching-Wei (Taipei, TW), Shih; KaeShyang (Taipei, TW), Wang; Chia-Lin J. (Taipei, TW) Assignee(s): Development Center for Biotechnology (TW) Patent Number: 5,710,280 Date filed: July 9, 1996 Abstract: A process for preparing fluconazole, including the steps of (1) acylating 1,3difluorobenzene (DFB) to obtain 2-chloro-2',4'-difluoroacetophenone (CAP); (2) alkylating 4-amino-4H-1,2,4-triazole (4-AT) with CAP to obtain 2-(1H-1,2,4-triazol-1-yl)2',4'-difluoroacetophenone (TAAP) salt; (3) deaminating TAAP salt to obtain TAAP; and (4) reacting TAAP with 1,2,4-triazole to obtain fluconazole. Excerpt(s): Fluconazole, i.e., 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan2-ol, is an antifungal agent developed by Pfizer Inc. The compound is useful for treating various fungal infections such as mycohemia, mycosis (both in the respiratory system and digestive system), and fungal meningitis, which are caused by, among others,

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various species of Candida, Coccidioides and Trichophyton. Fluconazole inhibits the biosynthesis of ergosterol, an important component of fungal cell membrane. The inhibition is highly specific to ergosterol biosynthesis in fungi. A method of preparing fluconazole can be found in U.S. Pat. No. 4,404,216 (1983). (1) acylating 1,3difluorobenzene (DFB), e.g., with a chloroacetyl halide, to obtain 2-chloro-2',4'difluoroaceto-phenone (CAP), preferably with aluminum trichloride as the catalyst and dichloromethane as the solvent. Web site: http://www.delphion.com/details?pn=US05710280__ •

Processes for the preparation of 1,3-bis(1,2,4-triazol-1-yl)-propan-2-ol derivatives Inventor(s): Senderichin; Alexander (Jerusalem, IL), Veinberg; Alexander (Rehovot, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (Jerusalem, IL) Patent Number: 5,484,936 Date filed: March 24, 1994 Abstract: The invention provides a regiospecific process for the preparation of 1,3bis(1,2,4-triazol-1-yl)-propan-2-ol derivatives comprising reacting an oxirane acid salt or an oxirane, under acidic conditions, with 4H-4-amino-1,2,4-triazole. The process is particularly useful for preparing fluconazole which is useful in the treatment of fungal infections in animals and humans. Excerpt(s): The present invention relates to a regiospecific process for the preparation of 1,3-bis(1,2,4-triazol-1-yl)-propan-2-ol derivatives. The preparation of fluconazole (IV) by alternative processes has been described in British Patent No. 2,099,818. In both cases, these reactions are not regiospecific and two isomers are observed in the product mixture. In British Patent 2,099,818 it is stated that, "the product will generally be contaminated with the isomer in which one of the triazole rings is attached to the adjacent CH.sub.2 via the 4-position." Therefore, the process of British Patent 2,099,818 discloses the need for column chromatography to isolate the desired product from the side product iso-fluconazole. Web site: http://www.delphion.com/details?pn=US05484936__

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

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

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Antifungal compounds and uses therefor Inventor(s): Crich, David; (Chicago, IL), Jaber, Mohammad-Rami; (Romeoville, IL), Johnson, Michael E.; (Winnetka, IL), Markham, Penelope N.; (Oak Park, IL), Mulhearn, Debbie C.; (Wheaton, IL), Neyfakh, Alexander A.; (Chicago, IL), Xuan, Yongzhi; (Chicago, IL) Correspondence: Steven L. Highlander; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20020193369 Date filed: November 2, 2001 Abstract: The present invention provides compounds which, when used in combination with antifungal azoles, offer enhanced antifungal therapy. More particularly, these compositions (including carbazoles or triptycenes) can convert fungistatic drugs such as fluconazole into fungicidal drugs. Excerpt(s): The present invention relates generally to the fields of fungal disease and antimicrobial agents. More particularly, it concerns drug combinations that show enhanced antifungal activity. The AIDS epidemic, advances in surgical procedures, and aggressive anticancer therapy have contributed to the surge of immunocompromised population. Coinciding with this surge is an increase in the incidence of clinically significant fungal infections (Dixon et al., 1996; Henderson and Hirvela, 1996). Candida albicans has become the fourth leading cause of nosocomial infections, with systemic candidiasis having a very high mortality rate, especially in newborns--up to 65% (Pacheco-Rias et al., 1997), and among cardiac surgery patients--up to 30% (Michaloupoulos et al., 1997). The majority of AIDS patients experience some form of candidiasis and many have to take antifungal drugs repeatedly, or even prophylactically on a daily basis. In the healthy population, more than half of all women experience at least one vaginal yeast infection, and about 8% suffer recurrent episodes. The morbidity, mortality and health care costs associated with fungal infections has commanded a need for effective antifungal agents. Only a few classes of antifungal drugs are actively used in clinics. Flucytosine, a substituted pyrimidine, is converted by a fungi-specifc cytosine deaminase into 5-fluorouracil which causes the inhibition of DNA and protein synthesis. Due to frequent emergence of resistance, flucytosine is rarely used alone and is often coadministered with amphotericin B (Alexander & Perfect, 1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Antifungal formulation and the methods for manufacturing and using the same Inventor(s): Chen, Ping-Kuen; (Taichung, TW), Chen, Shan-Chiung; (Taichung, TW), Kuo, Han-Chiang; (Taichung, TW), Lee, Fan-Yu; (Taichung, TW) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20020176894 Date filed: April 5, 2002 Abstract: The present invention provides novel pharmaceutical compositions for azole antimicrobial drugs such as itraconazole, saperconazole, ketoconazole, and fluconazole. The pharmaceutical compositions are in the form of pellets which comprise a core and a drug emulsion layer, and optionally, a protective layer. The drug emulsion layer

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contains the azole antimicrobial drug, an emulsifier, a binder, and an absorbent aid. The preferred emulsifier is vitamin E polyethylene glycol succinate. The preferred binder is hydroxypropyl methylcellulose. The preferred absorbent aid is DL malic acid. The drug is dissolved in organic solvents. The preferred organic solvents are ethanol and methylene chloride. The protective layer contains polyethylene glycol (PEG) 20,000, which is coated on the drug emulsion layer. Excerpt(s): The present invention relates to pharmaceutical compositions which comprise a core and a drug emulsion layer, and, optionally, a protective layer. The preferred core is a round, spherical core which comprises sucrose, lactose, starch, talc, or microcrystalline cellulose or any combination thereof. The preferred drug is an azole antifungal or antibacterial drug. Examples of the azole antifungal or antibacterial drug include, but are not limited to, itraconazole, saperconazole, ketoconazole, and fluconazole. The drug emulsion layer includes the drug, an emulsifier, a binder, and an absorbent aid. The preferred emulsifier is vitamin E polyethylene glycol succinate. The preferred binder is hydroxypropyl methylcellulose. The preferred absorbent aid is DL malic acid. The azole antifungal or antibacterial drug is preferably dissolved in organic solvents, such as ethanol and methylene chloride. The protective layer contains polyethylene glycol (PEG) 20,000 and is coated on the emulsified layer. The present invention also relates to a method for making the pharmaceutical preparation and methods of using the pharmaceutical preparation to treat patients with fungal or bacterial infections. U.S. Pat. No. 4,267,179 discloses a number of 1H-imidazole and 1H1,2,4-triazole derivatives having antifungal and antibacterial properties. Specifically, a number of heterocyclic derivatives of (4-phenyl-1-piperazinyl-aryloxymethyl-1,3dioxolan-2-yl) methyl-1H-imidazoles and 1H-1,2,4-triazoles are described. Among these azole compounds and their derivatives, itraconazole, saperconazole, ketoconazole, and fluconazole are currently commercially available. These commercially available azole compounds are known for their broad spectrum of antimicrobial activity. For example, they are found to be highly active against a wide variety of fungi such as Microsporum canis, Pityrosporum ovale, Ctenomyces mentagrophytes, Trichophyton rubrum, Phialophora verrucosa, Cryptococcus neoformans, Candida tropicalis, Candida albicans, Mucor species, Aspergillus fumigatus, Sporotricum schenckii and Saprolegnia species. They are also active against bacteria, such as Erysipelotrix insidiosa, Staphylococcus hemolyticus and Streptococcus pyogenes. Itraconazole is especially known for its activity against a broad range of fungal inductions such as those caused by Trichophyton rubrum, Tricophyton mentagrophytes, Epidermophyton floccsum and Candida albicans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antifungal remedy formulation for external application Inventor(s): Kim, Jun-Sik; (Gyunggi-do, KR), Kim, Sang-Lin; (Seoul, KR), Lee, Ho-Beom; (Gyunggi-do, KR), Min, Geun-Hong; (Gyunggi-do, KR), Ryou, Hae-Won; (Gyunggi-do, KR), Tan, Hyun-Kwang; (Seoul, KR) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20040122071 Date filed: January 16, 2004 Abstract: An antibacterial composition for external application, particularly, a remedial formulation for external use containing fluconazole is disclosed. The formulation comprises a base material, 0.1-5.0 percent by weight of fluconazole and 1.0-40.0 percent

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by weight of any one compound selected from a group consisting of fatty acid, fatty alcohol, higher fatty acid ester and lower alcohol based on weight of the base material. The composition according to the present invention has various advantages of a favorable absorption into a system through the skin of a human body and delivery of active material into horny layer of the skin, a reduced skin stimulation and an excellent stability. Therefore, the composition is efficiently useable in a medical treatment application for dermatomycosis-related infectious diseases including tinea pedis, tinea corporis, tinea cruris, tinea versicolor and/or candidiasis and the like. Excerpt(s): The present invention relates an antibacterial or antifungal(hereinafter referred to as "antifungal") composition for external application containing triazolebased agents such as fluconazole as an active component. The composition of the present invention ensures the transfer of active materials deep into the horny layer of skin of a human body system to enhance the treatment effect, absorption and penetration activities thereof. Particularly, by leading the delivery of the active component through the skin deep into the horny layer, the composition according to the present invention can provide a maximum remedial value of the active component as an antifungal active agent. It is known that antifungal formulations for external use, more particularly, pharmaceutical compositions containing tolnaftate resistant to fungi and/or bacteria or imidazole derivatives such as clotrimazole, ketoconazole and the like having activity for candida species are generally available for the remedy of diseases related to the fungi including fungal infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antiinfective combinations and their use for the topical treatment of fungal infections of the toenails and fingernails Inventor(s): Bohn, Manfred; (Hofheim, DE), Kraemer, Karl Theodor; (Langen, DE) Correspondence: Finnegan, Henderson, Farabow; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20010046478 Date filed: March 7, 2001 Abstract: A preparation comprising a combination of a topical and a systemic antimycotic and a physiologically acceptable lacquer base is suitable for the treatment and prophylaxis of onychomycoses. Preference is given to the use of water-insoluble lacquer preparations and a combination of at least one systemic antimycotic from the group of itraconazole, terbinafine and fluconazole or salts thereof with at least one topical antimycotic from the group of ciclopirox, 6-(2,4,4-trimethylpentyl)-1-hyd- roxy-4methyl-2(1H)-pyridone, amorolfine and butenafine or salts thereof. Excerpt(s): The present application claims benefit of priority of German patent application No. 1001 1081.9, filed Mar. 9, 2000, the disclosure of which is incorporated herein by reference in its entirety. Fungal infections of the toenails and fingernails (onychomycoses) are widespread around the world. This chronic pathological entity, which does not tend to heal by itself, is becoming increasingly important particularly in highly developed industrialized countries. Onychomycoses constitute the most common disorder of nails, comprising a proportion of up to 40%. The prevalence of onychomycoses is stated in the state of the art to be 2.8% to 8.4%. Mycoses of nails now account for about 30% of all dermatomycoses. Epidemiological studies show that 20% to 30% of patients with Tinea pedis also have onychomycosis. Many patients feel restricted

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in their social contacts especially when the onychomycosis is located on the fingernails where it is clearly visible. In addition, the pathological event results in a possible restriction of tactility, motility and manual abilities. The need for treatment also derives from the fact that onychomycoses contribute, as source of infection, to the spread of the disease from the nail to the free skin. In addition, they represent a risk of infection for a continually increasing population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of treatment of non-invasive mucositis Inventor(s): Lane, Edward M.; (Bridgeport, CT) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20040029893 Date filed: July 23, 2003 Abstract: This invention relates to a method of treating mucositis, and in particular fungal sinusitis in mammals, using oral medication, including azole antifungal agents such as, for example fluconazole and voriconazole, and with proton pump inhibitors such as esomeprazole. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/398,207, filed Jul. 23, 2002, Provisional Application No. 60/401,972, filed Aug. 7, 2002, and Provisional Application No. 60/407,182, filed Aug. 29, 2002. This invention relates to the field of medical science, and in particular to treatment of inflammatory conditions of the mucosa (mucositis), especially sinusitis and otitis media, and including acute maxillary sinusitis of fungal etiology, with orally administered drugs, such as azole antifungal drugs and proton pump inhibitors, including fluconazole, voriconazole and esomeprazole. Mucositis is an inflammation of the mucosa; sinusitis is a mucositis of the nasal and/or paranasal sinuses. The etiology of sinusitis, as of many other mucositis conditions, can be viral, bacterial, fungal, allergic, chemical, secondary to gastro-esophageal reflux disease (GERD) in the case of sinusitis, or due to combinations of several of these factors. The conditions may be acute, subacute, chronic or acute recurrent. A large segment of the population suffering from sinusitis or other mucositis (e.g., otitis media, mastoiditis, or vaginal, oral, colo-rectal and urinary tract inflammations), develop recurrences without any obvious cause. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel class of thiomorpholino substituted thiazoles Inventor(s): Macina, Orest Taras; (Pittsburgh, PA), Riviello, Christopher Mark; (Old Forge, PA), Sircar, Ila; (Clarks Summit, PA), Sircar, Jagadish Chandra; (Clarks Summit, PA), Yu, Dingwei Tim; (Easton, PA) Correspondence: Joseph W. Molasky & Associates; 4 S. Limekiln Pike; Chalfont; PA; 18914; US Patent Application Number: 20010000177 Date filed: December 5, 2000

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Abstract: Disclosed is a novel class of thiazole, thiadiazole, and oxadiazole compounds which are substituted at their nuclear carbons by aromatic moieties. These compounds exhibit antifungal activity against a variety of fungi including strains which have proven to be resistant to treatment with known antifungal agents such as Fluconazole. Excerpt(s): 1. This invention relates to a novel class of substituted azoles and, more specifically, diaryl substituted thiazoles, diaryl substituted thiadiazoles and diaryl substituted oxadiazoles, compounds which are useful in the treatment of fungal infections in mammals including humans. These compounds are active against a broad spectrum of fungi such as Candida albicans, Candida parpsilosis, Candida tropicalis, Candida krusei, Cryptococcus neoformans, Aspergillus fumigatus and Torulopsis glabrata. Moreover, compounds within this series are also active against Fluconazole resistant strains and isolates. 2. Opportunistic fungal infections are responsible for increased morbidity and mortality among patients suffering from AIDS and other immunocompromised diseases including infections resulting from neutropenia, cancer chemotherapy and organ transplantation (Annals N.Y. Acad. Sc., 544:1-3). 3. Moreover, until recently, the treatment of deep seated fungal infections has lagged behind the treatment of bacterial infections and only a few systemic agents are available for combatting these invasive pathogens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for preparing monohydrate and crystal modifications of fluconazole Inventor(s): Czibula, Laszlo; (Budapest, HU), Deutschne Juhasz, Ida; (Budapest, HU), Farkas, Jenone; (Budapest, HU), Hegedus, Istvan; (Budapest, HU), Hegedus, Janosne Kreidl nee Regina; (Budapest, HU), Kreidl, Janos; (Budapest, HU), Nagyne Bagdy, Judit; (Budapest, HU), Piller, Agnes; (Budapest, HU), Szantay, Csaba; (Budapest, HU), Werkne Papp, Eva; (Budapest, HU) Correspondence: The Firm OF Karl F Ross; 5676 Riverdale Avenue; PO Box 900; Riverdale (bronx); NY; 10471-0900; US Patent Application Number: 20040106804 Date filed: September 22, 2003 Abstract: A new process is disclosed for the synthesis of fluconazole monohydrate and for crystal modifications of fluconazole which comprises the step of hydrolyzing a silyl ether of the formula (II) 1whereinR.sup.2 is hydrogen, or a C.sub.1 to C.sub.10 alkyl or phenyl group, R.sup.3 and R.sup.4 independently of each other are a C.sub.1 to C.sub.10 alkyl or phenyl group in an aqueous solution, preferably at a pH below 3 or above 8. Excerpt(s): This application is a continuation-in-part of International Application PCT/HU01/00033, with an international filing date of 23 Mar. 2001, published in English under PCT Article 21(2) and now abandoned. Here and further on terms crystal modification and polymorph modification have the same meaning and are used as synonyms. wherein the meaning of R is alkyl, cycloalkyl, aryl or aralkyl group, or the derivatives of these containing one or two halogen atoms or alkoxy, phenyl, phenoxy or trifluoromethyl substituted aryl and benzyl groups and Y.sup.1 and Y.sup.2 independently are --N.dbd. or --CH.dbd. group. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with fluconazole, 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 “fluconazole” (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 fluconazole. You can also use this procedure to view pending patent applications concerning fluconazole. 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 FLUCONAZOLE Overview This chapter provides bibliographic book references relating to fluconazole. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on fluconazole include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

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

Candidiasis (Thrush) Source: in Sutton, A.L. Dental Care and Oral Health Sourcebook. 2nd ed. Detroit, MI: Omnigraphics. 2003. p. 489-490. Contact: Available from Omnigraphics. 615 Griswold Street, Detroit, MI 48226. (313) 961-1340. Fax: (313) 961-1383. E-mail: [email protected]. www.omnigraphics.com. PRICE: $78.00; plus shipping and handling. ISBN: 780806344. Summary: Candidiasis of the mouth and throat (thrush) is a fungal infection that occurs when there is an overgrowth of fungus called Candida. This chapter on candidiasis is from a book that provides information about dental care and oral health at all stages of life. The chapter describes oropharyngeal candidiasis (OPC), the symptoms of OPC, transmission, diagnostic tests used to confirm OPC, treatment options, and resistance of OPC to treatment. Prescription treatments such as oral fluconazole, clotrimazole troches, or nystatin suspension usually provide effective treatment for OPC. Candida is normally found on skin or mucous membranes. However, if the environment inside the

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mouth or throat becomes imbalanced, Candida can multiply and symptoms of thrush can appear. •

Topical and Systemic Antifungal and Antiviral Agents Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 6988. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: This chapter on topical and systemic antifungal and antiviral agents is from a textbook that integrates basic facts and principles of antibiotic therapy with recentlyemerged concepts of care. The author notes that the last decade has seen an increase in the number of agents available for the treatment of fungi and viruses, in part due to research in treatments for people with HIV. The chapter covers only drugs already released or soon to be released by the FDA (Food and Drug Administration). Antifungals discussed are polyenes, including amphotericin B and nystatin; azoles, including ketoconazole, fluconazole, itraconazole, miconazole nitrate, clotrimazole, and topical azoles; allylamines and benzylamines; and miscellaneous antifungal drugs, including flucytosine, griseofulvin, potassium iodide, and topical agents. Antiviral agents discussed are nucleoside and nucleotide analogues, including acyclovir, valacyclovir hydrochloride, penciclovir, famciclovir, cidofovir, vidarabine, trifluridine, and idoxuridine, and ribavirin; pyrophosphate analogue, notably foscarnet sodium; carbon ring amines, including amantadine and rimantadine; neuraminidase inhibitors, including zanamivir and oseltamivir; recombinant protein; antisense oligonucleotide (fomivirsen); and a monoclonal antibody (palivizumab). For each drug, the author reviews indications, distribution in the body, adverse effects, the spectrum of efficacy, and drug variations (form and use). The chapter concludes with a review of the treatment of common oral fungal and viral infections. Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 2 figures. 5 tables. 17 references.

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

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

Caspofungin equivalent to fluconazole for esophageal candidiasis Source: Reuters Industry Breifing Date: October 31, 2002

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Non-C. albicans strains show less susceptibility to fluconazole over time in HIVinfected women Source: Reuters Medical News Date: February 02, 2001

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No evidence of benefit from fluconazole prophylaxis in ICU Source: Reuters Medical News Date: June 05, 2000

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Pfizer plans to distribute fluconazole free to South Africans with HIV, AIDS Source: Reuters Medical News Date: April 05, 2000

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Candida colonization in HIV+ women taking fluconazole shifts to less susceptible species Source: Reuters Medical News Date: May 10, 1999

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GM-CSF plus fluconazole may enhance treatment for HIV-related cryptococcosis Source: Reuters Medical News Date: January 13, 1999

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Weekly fluconazole effective fungal infection prophylaxis in HIV-positive patients Source: Reuters Medical News Date: January 12, 1999

•

Continuous fluconazole reduces relapse of HIV-related oral candidiasis Source: Reuters Medical News Date: July 24, 1998

•

Disc Diffusion Test Detects Fluconazole Resistance In C. Albicans Source: Reuters Medical News Date: November 14, 1997

•

Despite Resistance, Fluconazole Effective For Subset Of HIV-Positive Individuals Source: Reuters Medical News Date: October 03, 1996

•

Continuous Fluconazole Protects Against Oral Candida Source: Reuters Medical News Date: April 05, 1996

•

High-Dose Fluconazole Can Cause Alopecia Source: Reuters Medical News Date: September 07, 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.

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Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “fluconazole” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “fluconazole” (or synonyms). If you know the name of a company that is relevant to fluconazole, 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 “fluconazole” (or synonyms).

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

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periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for fluconazole. 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 fluconazole. 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 fluconazole: Antifungals, Azole •

Systemic - U.S. Brands: Diflucan; Nizoral; Sporanox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202697.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. 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 Institute10: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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

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•

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

•

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “fluconazole” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 5308 1 475 867 13 6664

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

13

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

14

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

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

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

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

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

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

•

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

18 Adapted 19

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

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

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

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

Cryptococcal Infection Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org. Summary: This fact sheet, for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), provides information about the cryptococcal infection or cryptococcosis. Cryptococcus, a fungus, probably enters the body when individuals breathe in air containing dust, particles of dried soil, or bird droppings. This infection often affects the meninges or the lining of the spinal cord, and may also cause pneumonia or widespread disease. The symptoms of cryptococcosis include fever, headache, stiff neck, nausea, vomiting, problems with vision, confused thinking, cough, shortness of breath, chest pain, and sores on the skin. Cryptococcosis is most often diagnosed using a spinal tap or blood work. This infection can be treated with fluconazole or amphotericin. Individuals with HIV can help to prevent cryptococcosis by taking fluconazole.

Patient Resources

•

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Esophageal Candidiasis Contact: Community AIDS Treatment Information Exchange, PO Box 1104, Toronto, (416) 203-7122, http://www.catie.ca. Summary: This fact sheet, for persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses the infection esophageal candidiasis, an AIDS-defining illness, which is caused by an overgrowth of candida. It discusses symptoms, which can include difficulty swallowing, a sore throat, and chest pain behind the breastbone; its diagnosis; and its prevention through using antiretroviral therapy for HIV/AIDS, reducing intakes of sugars and starchy foods, and eating unsweetened yogurt with live bacteria culture. It discusses the medical treatments of fluconazole, itraconazole, intravenous fluconazole, and amphotericin B.

•

Cryptococcal Meningitis Contact: University of New Mexico School of Medicine, New Mexico AIDS Education and Training Center, New Mexico AIDS InfoNet, PO Box 810, Arroyo Seco, NM, 87514, (505) 776-8032, http://www.aidsinfonet.org. Summary: This information sheet discusses cryptococcal meningitis, an opportunistic infection caused by a fungus often found in the soil. It enters the body when breathed in as dust and affects the lining of the spinal cord or brain, causing illness or death. The risk of cryptococcal infection increases when T-cell counts fall below 100. The information sheet explains the symptoms, diagnosis, treatment, and prevention of this disease. Cryptococcal meningitis is often diagnosed using lab tests that involve samples of spinal fluid, which are drawn through a spinal tap. Meningitis is treated using antifungal medications such as amphotericin B, fluconazole, and flucytosine used by themselves or in combinations. Repeat cases of meningitis may be reduced if individuals keep taking anti-fungal drugs. Taking fluconazole can help to reduce the likelihood of cryptococcal meningitis when CD4 cell counts are below 50. The NIH Search Utility

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

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•

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

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

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

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

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

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

21

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

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

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

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

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

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

•

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

•

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

22

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

Finding Medical Libraries

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•

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

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

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

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

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

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

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

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

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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

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

•

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

Finding Medical Libraries

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

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

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

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

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

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

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

•

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

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

•

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

•

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

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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).

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

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

•

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

•

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

•

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

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FLUCONAZOLE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acanthamoeba: A genus of free-living soil amoebae that produces no flagellate stage. Its organisms are pathogens for several infections in humans and have been found in the eye, bone, brain, and respiratory tract. [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] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH]

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Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [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] Allogeneic: Taken from different individuals of the same species. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of

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Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [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] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test

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new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [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] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU]

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Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aqueous: Having to do with water. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [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] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autopsy: Postmortem examination of the body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH]

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Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzylamines: Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group. [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] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] 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] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the

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lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [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] 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 Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromazepam: A benzodiazepine that is used in the treatment of anxiety disorders. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [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

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many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogenicity: The ability to cause cancer. [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] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] 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] Caspofungin acetate: A drug used to prevent or treat infections caused by a fungus (a type of microorganism). It belongs to the family of drugs called antifungal agents. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [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] 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 Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Division: The fission of a cell. [NIH]

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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 Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] 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] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] 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] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH]

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Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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] Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical 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] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [NIH] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [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] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU]

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Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conjugated: Acting or operating as if joined; simultaneous. [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]

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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Consolidation therapy: Chemotherapy treatments given after induction chemotherapy to further reduce the number of cancer cells. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptococcus: A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium. [NIH]

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Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] 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] Cyclophilins: A family of peptidyl-prolyl cis-trans isomerases that bind to cyclosporins and regulate the immune system. EC 5.2.1.- [NIH] Cyclosporins: A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytomegalovirus Retinitis: Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH]

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Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [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]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatomycoses: Superficial infections of the skin or its appendages by any of various fungi. [NIH] Dermatomycosis: A superficial infection of the skin or its appendages by fungi. The term includes dermatophytosis and the various clinical forms of tinea, as well as deep fungous infections. Called also epidermomycosis. [EU] Dermatophytosis: Any superficial fungal infection caused by a dermatophyte and involving the stratum corneum of the skin, hair, and nails. The term broadly comprises onychophytosis and the various form of tinea (ringworm), sometimes being used specifically to designate tinea pedis (athlete's foot). Called also epidermomycosis. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH]

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Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [NIH] Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to didanosine (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Diploidy: The chromosomal constitution of somatic cells, in which each type of chromosome is represented twice. Symbol: 2N or 2X. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is

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roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Dross: Residue remaining in an opium pipe which has been smoked; contains 50 % of the morphine present in the original drug. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH]

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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] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the

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eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermomycosis: An infection caused by dermatophytes. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] 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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esterification: The process of converting an acid into an alkyl or aryl derivative. Most

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frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [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] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Eucalyptus: A genus of Australian trees of the Myrtaceae family that yields gums, oils, and resins which are used as flavoring agents, astringents, and aromatics, and formerly to treat diarrhea, asthma, bronchitis, and respiratory tract infections. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Flatus: Gas passed through the rectum. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Flexor: Muscles which flex a joint. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an

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antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Foscarnet: An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [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] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH]

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Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geotrichosis: Infection due to the fungus Geotrichum. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [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] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [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] 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] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU]

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Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Griseofulvin: An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [NIH] Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH]

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Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH]

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Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Idoxuridine: An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent, particularly in the treatment of herpes simplex keratitis. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the

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administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] 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,

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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 signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well

Dictionary 179

as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invertebrates: Animals that have no spinal column. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratitis: Inflammation of the cornea. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kinetic: Pertaining to or producing motion. [EU]

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Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Linkages: 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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH]

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Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] 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-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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [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] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH]

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Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastoiditis: Inflammation of the cavity and air cells in the mastoid part of the temporal bone. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Maxillary Sinus: One of the paired paranasal sinuses, located in the body of the maxilla, communicating with the middle meatus of the nasal cavity. [NIH] Maxillary Sinusitis: Inflammation of the maxillary sinus. In most cases it is the result of infection by the bacteria Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. This condition may be acute or chronic. [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] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] 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] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH]

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Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes 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] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

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Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mycological: Relating to mycology, that is the science and study of fungi. [EU] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to

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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] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light

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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] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitrofurantoin: A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and longterm suppression. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nystatin: Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex are nystatin A1, A2, and A3. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides

Dictionary 187

connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] Oncology: The study of cancer. [NIH] Onychomycosis: Mycosis of the nails, possibly due to some extent to humidity. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [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]

Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] 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

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gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [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] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptic Ulcer Perforation: Penetration of a peptic ulcer through the stomach wall. May be free, i.e., at a point where the stomach wall faces a real or potential space, or confined, i.e., at a point where the stomach wall is defended by contiguous or adjacent structures, such as the pancreas. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of

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proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral blood: Blood circulating throughout the body. [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] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [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] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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]

Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms.

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[NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] 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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] 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] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Polyploid: An organism with more than two chromosome sets in its vegetative cells. [NIH] Polyploidy: The chromosomal constitution of a cell containing multiples of the normal

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number of chromosomes; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc. [NIH]

Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postoperative: After surgery. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] 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] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] 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]

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Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prophylaxis: An attempt to prevent disease. [NIH] Propolis: Resinous substance obtained from beehives; contains many different substances which may have antimicrobial or antimycotic activity topically; its extracts are called propolis resin or balsam. Synonyms: bee bread; hive dross; bee glue. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [NIH]

Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of

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cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [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 Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies

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in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] 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] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU]

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Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal Replacement Therapy: Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. [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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [NIH] Rimantadine: An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] 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

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dilutions. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [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] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition

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causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Sodium salicylate: A drug that belongs to the family of drugs called nonsteroidal antiinflammatory drugs. Sodium salicylate may be tolerated by people who are sensitive to aspirin. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH]

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Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sporotrichosis: The commonest and least serious of the deep mycoses, characterized by nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subungual: Beneath a nail. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfadiazine: A short-acting sulfonamide used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [NIH] Support group: A group of people with similar disease who meet to discuss how better to

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cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talc: A native magnesium silicate. [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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Tinea Pedis: Dermatological pruritic lesion in the feet, caused by Trichophyton rubrum, T. mentagrophytes, or Epidermophyton floccosum. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by

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other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolnaftate: A synthetic antifungal agent. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Torsades de Pointes: A ventricular tachycardia characterized by periodic twisting of the points of the QRS complexes and rates between 200 and 250 beats per minute. It may be selflimited or may progress to ventricular fibrillation. [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] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH]

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Translocation: The movement of material in solution inside the body of the plant. [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 Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [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]

Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH]

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Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valganciclovir: An antiviral agent that is being studied as a treatment for AIDS-related cytomegalovirus. It is converted in the body to ganciclovir. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Varicella: Chicken pox. [EU] Variegation: The appearance of different kinds of tissue in patterns, patches, or bands, frequently caused by the presence of special pigments or the absence of normal pigments. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [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] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU]

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Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia virus and varicella zoster virus. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voriconazole: A drug that treats infections caused by fungi. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Vulvovaginitis: Inflammation of the vulva and vagina, or of the vulvovaginal glands. [EU] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xamoterol: A selective beta-1-adrenergic partial agonist. Because it is a partial agonist it acts like an agonist when sympathetic activity is low and as an antagonist when sympathetic activity is high. It reduces myocardial ischemia and improves ventricular function in patients with mild to moderate heart failure. In patients with severe heart failure it has been shown to produce benefits in systolic and diastolic function. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The

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compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH]

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INDEX A Abdominal, 153, 187, 188, 189 Abdominal Pain, 153, 189 Acanthamoeba, 61, 153 Acceptor, 153, 187 Acetaminophen, 153, 172 Acquired Immunodeficiency Syndrome, 63, 100, 153, 198 Acute myelogenous leukemia, 70, 153 Acute myeloid leukemia, 153, 192 Acute nonlymphocytic leukemia, 153 Acyclovir, 60, 124, 153, 172 Acyl, 153, 171 Adjustment, 54, 83, 153 Adjuvant, 24, 153 Adrenergic, 153, 155, 168, 203 Adverse Effect, 4, 124, 153, 196 Aerobic, 154, 183 Aerosol, 154, 199 Affinity, 96, 105, 106, 154, 181, 197 Agar, 30, 31, 32, 35, 41, 51, 52, 80, 81, 154, 165, 177, 190 Agonist, 154, 168, 203 Agranulocytosis, 59, 154 Algorithms, 154, 158 Alimentary, 154, 179, 188 Alkaline, 154, 155, 159, 189 Allogeneic, 18, 49, 66, 67, 154, 175 Allografts, 112, 154 Alpha Particles, 154, 193 Alpha-1, 154, 155 Alternative medicine, 127, 154 Aluminum, 116, 154 Amantadine, 124, 154 Amino acid, 60, 96, 106, 155, 156, 170, 173, 176, 188, 190, 192, 196, 198, 200, 201 Amino Acid Sequence, 155, 156 Amino Acid Substitution, 36, 60, 96, 106, 155 Amitriptyline, 52, 79, 155 Ammonia, 155, 199, 201 Amnestic, 155, 172, 183 Anaesthesia, 83, 155, 177 Analgesic, 153, 155, 176 Analog, 153, 155, 171, 172, 176 Anaphylatoxins, 155, 163 Anatomical, 155, 177 Anemia, 155, 204

Anesthesia, 155, 183 Anginal, 155, 186 Animal model, 15, 22, 40, 155 Antibacterial, 112, 118, 119, 156, 197 Antibiotic, 4, 7, 10, 11, 22, 112, 114, 124, 156, 159, 170, 172, 174, 186, 195, 197, 203 Antibodies, 38, 104, 156, 174, 177, 181, 190, 193 Antibody, 124, 154, 156, 163, 174, 177, 184, 193, 194, 197 Anticholinergic, 155, 156 Anticonvulsant, 156, 183, 202 Antigen, 18, 29, 154, 156, 163, 177 Antigen-Antibody Complex, 156, 163 Anti-infective, 156, 186 Anti-inflammatory, 153, 156, 157, 164, 176, 195, 197 Antimetabolite, 153, 156, 171, 195 Antimycotic, 119, 156, 162, 192 Antineoplastic, 93, 103, 114, 156, 164, 165, 171, 187, 203 Antineoplastic Agents, 93, 103, 156 Antioxidants, 56, 94, 156 Antiviral, 89, 124, 153, 154, 156, 157, 172, 176, 178, 195, 202, 203 Antiviral Agents, 124, 157 Anus, 157, 159, 179, 194 Anxiety, 100, 157, 159, 172, 186, 188 Anxiety Disorders, 157, 159, 188 Anxiolytic, 157, 183 Aorta, 157, 174 Aqueous, 121, 157, 165, 169 Archaea, 157, 183 Arterial, 157, 176, 192, 199 Arteries, 157, 159, 164, 174, 181, 183, 185 Arterioles, 157, 159, 160, 185 Aspergillosis, 7, 18, 114, 157, 179 Aspirin, 157, 197 Assay, 26, 29, 42, 52, 96, 157 Astringents, 157, 171 Attenuated, 157, 167, 201 Autologous, 157, 175 Autologous bone marrow transplantation, 157, 175 Autopsy, 55, 157 B Bacterial Infections, 18, 115, 118, 121, 157, 161, 180

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Bactericidal, 157, 171 Bacteriophage, 157, 190, 200 Bacteriostatic, 158, 170 Basophils, 154, 158, 174, 180 Benign, 7, 113, 158, 174, 185, 194 Benzene, 158 Benzylamines, 124, 158 Bile, 158, 172, 181, 198 Bioassay, 42, 158 Bioavailability, 20, 40, 47, 113, 158 Bioavailable, 113, 158 Biochemical, 21, 22, 24, 101, 106, 156, 158, 196 Biofilms, 12, 38, 158 Biological Transport, 158, 167 Biopsy, 8, 158 Biosynthesis, 11, 12, 99, 104, 116, 158, 162, 181, 192 Biotechnology, 27, 43, 93, 94, 115, 127, 135, 158 Bladder, 77, 78, 158, 163, 201 Blastomycosis, 7, 70, 158, 179 Blister, 64, 159 Blood Coagulation, 159 Blood pressure, 71, 159, 176, 184, 186, 197 Blood vessel, 159, 170, 182, 189, 193, 197, 199, 202 Body Fluids, 159, 195, 197 Bone Marrow, 29, 41, 75, 114, 153, 157, 158, 159, 174, 175, 181, 184, 191, 192, 197, 204 Bone Marrow Cells, 159, 174 Bowel, 159, 167, 180, 189 Bowel Movement, 159, 167 Broad-spectrum, 4, 159, 195 Bromazepam, 55, 159 Bronchitis, 159, 171 Buccal, 93, 159, 198 Burns, 59, 159 Burns, Electric, 159 C Calcineurin, 22, 83, 104, 159 Calcium, 8, 159, 160, 163, 186 Calmodulin, 159, 160 Candidosis, 6, 7, 44, 62, 67, 89, 160 Capillary, 26, 29, 160, 202 Capsules, 41, 160, 170 Carbohydrate, 93, 103, 160, 164, 191 Carbon Dioxide, 80, 160, 166, 172, 190, 195 Carcinogenic, 64, 158, 160, 178, 192, 198 Carcinogenicity, 64, 160 Carcinoma, 160

Cardiac, 112, 117, 160, 169, 175, 180, 183, 184, 185, 198 Cardiorespiratory, 160, 183 Case report, 47, 73, 82, 160 Caspofungin acetate, 83, 160 Catheter, 13, 160 Causal, 16, 160 Cause of Death, 114, 160 Cell Count, 5, 71, 141, 160 Cell Division, 157, 160, 183, 190, 196 Cell membrane, 22, 101, 116, 158, 161, 162, 197 Cell Respiration, 161, 183, 195 Cell Transplantation, 161, 175 Cellobiose, 161 Cellulose, 118, 161, 172, 182, 190 Central Nervous System, 114, 158, 159, 161, 174, 196 Central Nervous System Infections, 161, 174 Centrifugation, 161, 183 Cerebral, 44, 161 Cerebrospinal, 40, 65, 161, 181, 197 Cerebrospinal fluid, 40, 65, 161, 181, 197 Cerebrum, 161 Cheilitis, 4, 161 Chemical Warfare, 161, 166 Chemical Warfare Agents, 161, 166 Chemotactic Factors, 161, 163 Chest Pain, 140, 141, 161 Chlorophyll, 161, 172 Cholecystitis, 47, 161 Cholesterol, 12, 27, 158, 162, 181, 198 Cholinergic, 155, 162 Chromatin, 16, 162 Chromatography, Liquid, 11, 162 Chromosomal, 16, 19, 162, 167, 175, 190 Chromosome, 16, 19, 162, 167, 174, 179, 180, 190, 196 Chronic, 3, 8, 12, 51, 107, 113, 114, 119, 120, 159, 162, 170, 178, 180, 182, 196, 198 Chronic Disease, 3, 162, 180 Chronic lymphocytic leukemia, 51, 162 Cidofovir, 124, 162 CIS, 26, 162, 165 Clinical trial, 8, 92, 135, 162, 168, 184, 192, 194 Cloning, 158, 162, 178 Clotrimazole, 4, 6, 7, 32, 119, 123, 124, 162 Coccidioidomycosis, 32, 35, 81, 102, 162 Coenzyme, 162, 181 Cofactor, 162, 192

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Collagen, 100, 155, 162, 171, 192 Colloidal, 28, 92, 162, 169, 189, 199 Combinatorial, 10, 15, 163 Commensal, 113, 163 Complement, 11, 155, 163, 179 Complementary and alternative medicine, 99, 107, 163 Complementary medicine, 99, 163 Compliance, 6, 22, 163 Computational Biology, 135, 163 Conception, 163, 164 Conjugated, 163, 165 Connective Tissue, 159, 162, 163, 164, 166, 182, 195 Consolidation, 84, 164 Consolidation therapy, 84, 164 Constipation, 164, 189 Contamination, 164, 175 Contraceptive, 94, 164 Contraindications, ii, 7, 164 Cornea, 164, 179, 204 Corneum, 47, 66, 69, 164, 166, 170, 176 Coronary, 164, 183, 185 Coronary Thrombosis, 164, 183, 185 Cortex, 164, 171, 187, 191 Corticosteroid, 164, 198 Cranial, 164, 174 Craniocerebral Trauma, 164, 174, 200 Critical Care, 25, 58, 164 Crossing-over, 164, 194 Cryptococcosis, 7, 22, 77, 89, 102, 114, 126, 140, 164 Culture Media, 154, 165 Curative, 165, 199 Cutaneous, 45, 54, 70, 89, 158, 160, 165, 198, 201 Cyanide, 165, 183 Cyclic, 8, 33, 160, 165 Cyclophilins, 22, 165 Cyclosporins, 165 Cytochrome, 27, 31, 72, 88, 102, 105, 165 Cytokine, 165, 196 Cytomegalovirus, 165, 172, 202 Cytomegalovirus Infections, 165, 172 Cytomegalovirus Retinitis, 165, 172 Cytoplasm, 158, 161, 165, 170 Cytosine, 35, 60, 117, 165, 171 Cytotoxic, 114, 165, 177, 193, 194 D De novo, 11, 165 Decontamination, 112, 166 Degenerative, 166, 175

Delavirdine, 34, 166, 186 Delivery of Health Care, 166, 174 Dementia, 153, 166 Demethylation, 27, 166 Density, 16, 161, 166, 187, 190 Dental Care, 123, 166 Dental Caries, 166 Dental Plaque, 12, 166 Dermal, 166, 180 Dermatomycoses, 119, 166 Dermatomycosis, 119, 166 Dermatophytosis, 166 Dermis, 69, 166, 199 Desensitization, 166, 177 Deuterium, 166, 176 Diagnostic procedure, 111, 127, 166 Diarrhea, 167, 171 Diastolic, 167, 176, 203 Didanosine, 45, 167 Dideoxyadenosine, 167 Dietary Fats, 167, 180 Diffusion, 28, 32, 33, 34, 35, 41, 42, 45, 51, 52, 53, 55, 57, 93, 102, 126, 158, 167, 177 Digestion, 154, 158, 159, 167, 180, 181, 188, 198 Digestive system, 115, 167, 184 Digestive tract, 113, 167 Dihydrotestosterone, 167, 194 Dilution, 30, 31, 167 Diploid, 16, 22, 167, 190 Diploidy, 16, 167 Direct, iii, 17, 19, 129, 167, 168, 194 Discrete, 167, 180, 204 Disinfectant, 167, 171 Dissociation, 154, 167 Distal, 76, 168 Dopamine, 155, 168, 185 Dose-dependent, 168, 204 Double-blind, 18, 44, 45, 49, 54, 56, 58, 79, 88, 168 Dross, 168, 192 Drug Combinations, 117, 168 Drug Interactions, 6, 7, 19, 20, 22, 26, 45, 68, 130, 168 Drug Resistance, 11, 12, 13, 16, 25, 56, 101, 168 Drug Tolerance, 168 Duodenum, 158, 168, 170, 188, 198 Dura mater, 168, 182, 187 E Effector, 163, 168

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Fluconazole

Efficacy, 7, 21, 26, 35, 38, 43, 44, 55, 56, 71, 84, 86, 87, 92, 104, 124, 168 Elastin, 162, 168 Electroencephalography, 55, 168 Electrolyte, 164, 169, 175, 191, 197 Electrons, 169, 179, 187, 193, 194 Electrophoresis, 26, 169, 177 Emaciation, 153, 169 Embryo, 169, 177 Empirical, 20, 48, 169 Emulsion, 117, 118, 169 Encapsulated, 45, 169, 181 Encephalitis, 61, 169 Encephalitis, Viral, 169 Endocarditis, 30, 31, 32, 35, 36, 70, 160, 169 Endocardium, 169 Endogenous, 87, 168, 169, 192, 200 Endopeptidases, 169, 192 Endophthalmitis, 31, 35, 75, 79, 86, 87, 94, 169 Endoscopic, 170, 183 Endothelial cell, 38, 169, 170 Endotoxins, 163, 170 Enteric-coated, 45, 170 Environmental Health, 134, 136, 170 Enzymatic, 27, 155, 160, 163, 166, 167, 170, 171 Enzyme, 19, 20, 27, 114, 155, 162, 168, 170, 180, 181, 185, 188, 190, 192, 194, 195, 198, 200, 203 Eosinophil, 170, 174 Eosinophilia, 59, 170 Epidemic, 117, 170 Epidermal, 170, 180 Epidermis, 69, 159, 164, 166, 170, 176, 180 Epidermomycosis, 166, 170 Epigastric, 170, 187 Epithelial, 93, 158, 170, 175 Epithelial Cells, 93, 170, 175 Erythrocytes, 155, 159, 170 Erythromycin, 20, 170 Esophageal, 6, 21, 45, 55, 120, 125, 141, 170 Esophagitis, 7, 170 Esophagus, 6, 167, 170, 188, 189, 194, 198 Esterification, 27, 170 Estradiol, 26, 171 Estrogen, 171 Ethanol, 103, 118, 171 Ether, 121, 157, 171 Ethinyl Estradiol, 26, 171 Eucalyptus, 101, 171 Exocrine, 171, 187

Exogenous, 169, 171, 192 Extracellular, 34, 56, 158, 163, 164, 171, 183, 197 Extracellular Matrix, 163, 164, 171 Extracellular Space, 171, 183 Extraction, 20, 70, 171 Extrapyramidal, 155, 168, 171 F Family Planning, 135, 171 Fat, 159, 164, 171, 180, 181, 195, 197 Fibroblasts, 101, 112, 171 Flatus, 171, 172 Flavoring Agents, 171 Flexor, 171, 180 Flucytosine, 4, 22, 28, 30, 31, 33, 34, 35, 37, 58, 60, 65, 80, 81, 117, 124, 141, 171 Fluorouracil, 117, 171 Fluoxetine, 26, 171 Fluvoxamine, 19, 172 Fold, 19, 172 Follicles, 172 Folliculitis, 50, 51, 172 Forearm, 159, 172 Foscarnet, 124, 172 Fulminant Hepatic Failure, 83, 172 Fungemia, 47, 52, 75, 172 Fungicides, Industrial, 156, 172 Fungus, 8, 84, 123, 140, 141, 160, 162, 164, 172, 173, 184 G Gallbladder, 153, 161, 167, 172 Gamma Rays, 172, 193, 194 Ganciclovir, 18, 60, 172, 202 Gas, 29, 42, 60, 61, 155, 160, 167, 171, 172, 176, 186, 193, 195, 198, 199, 202 Gas exchange, 172, 195, 202 Gastric, 172, 187, 188 Gastric Juices, 172, 188 Gastrointestinal, 6, 75, 171, 172, 173, 196, 198 Gastrointestinal tract, 171, 173, 196 Gene, 12, 16, 17, 18, 22, 23, 26, 27, 33, 43, 64, 84, 100, 104, 158, 173, 178, 179, 181, 196 Gene Duplication, 16, 173 Gene Expression, 16, 17, 22, 23, 24, 33, 100, 104, 173 Gene Library, 173 Gene Silencing, 16, 173 Genetics, 16, 17, 21, 74, 173 Genomic Library, 17, 173 Genotype, 154, 173, 189

209

Geotrichosis, 7, 173 Gingivitis, 166, 173 Gland, 164, 173, 187, 196, 198, 199 Glomerular, 173, 195 Glomeruli, 173, 193 Glucose, 31, 41, 80, 161, 173, 178, 195 Glycine, 155, 173, 185 Glycoprotein, 173, 174, 181 Glycosidic, 161, 173, 185, 187 Gonadal, 173, 198 Governing Board, 173, 191 Graft, 154, 165, 173 Gram-negative, 173, 186 Gram-positive, 174, 186 Granulocyte, 61, 83, 174 Granulocyte-Macrophage ColonyStimulating Factor, 83, 174 Griseofulvin, 66, 84, 124, 174 H Haematological, 55, 92, 100, 174 Haematology, 55, 67, 92, 100, 174 Hair follicles, 166, 172, 174 Haploid, 174, 190 Haptens, 154, 174 Headache, 101, 140, 174, 178 Headache Disorders, 174 Health Care Costs, 117, 174 Health Expenditures, 174 Health Status, 7, 174 Heart failure, 174, 203 Heart Valves, 112, 174 Hematologic malignancies, 48, 175 Hematopoietic Stem Cell Transplantation, 18, 80, 175 Heme, 165, 175 Hemodiafiltration, 79, 175 Hemodialysis, 175 Hemofiltration, 175 Hemorrhage, 164, 165, 174, 175 Hepatic, 20, 80, 175 Hepatitis, 46, 83, 172, 175 Hepatitis A, 46, 175 Hepatocytes, 19, 175 Hepatotoxicity, 68, 82, 175 Hepatovirus, 175 Heredity, 173, 175 Herpes, 153, 175, 176, 203 Herpes virus, 175, 203 Heterogeneity, 73, 154, 175 Heterotrophic, 172, 175 Histones, 159, 162, 175 Homeostasis, 93, 104, 176

Hormonal, 64, 164, 176 Hormone, 158, 164, 171, 176, 178, 182, 191, 199 Hybrid, 22, 27, 176 Hydrogen, 121, 153, 158, 160, 166, 167, 176, 184, 186, 187, 192 Hydrolysis, 161, 176, 185, 190, 192 Hydroxylysine, 162, 176 Hydroxyproline, 155, 162, 176 Hyperplasia, 176, 180 Hypertension, 174, 176, 200 Hypertrophy, 176 Hypnotic, 176, 183 I Ibuprofen, 33, 176 Ichthyosis, 77, 176 Idoxuridine, 124, 176 Imidazole, 39, 118, 119, 162, 176, 183 Immune function, 22, 176, 177 Immune response, 153, 156, 164, 174, 176, 177, 198, 203 Immune system, 6, 165, 176, 177, 181, 189, 203 Immunocompromised, 4, 9, 13, 22, 78, 89, 115, 117, 121, 176 Immunocompromised Host, 4, 176 Immunodeficiency syndrome, 177 Immunodiffusion, 154, 177 Immunoelectrophoresis, 154, 177 Immunoglobulin, 156, 177, 184 Immunologic, 6, 161, 176, 177, 194, 204 Immunology, 25, 71, 82, 99, 105, 153, 154, 177 Immunophilin, 159, 177 Immunosuppressant, 171, 177 Immunosuppression, 7, 9, 177, 181, 187 Immunosuppressive, 7, 22, 27, 114, 159, 165, 177, 199 Immunosuppressive Agents, 27, 177 Impairment, 4, 177 In vivo, 11, 13, 19, 20, 21, 28, 31, 32, 37, 88, 95, 105, 167, 177, 181, 183, 199 Incision, 177, 179 Incubation, 39, 95, 177 Induction, 35, 38, 70, 71, 118, 164, 177 Infarction, 164, 177, 183, 185 Influenza, 155, 178, 195 Infusion, 178, 183, 200 Inhalation, 154, 162, 178, 183, 190, 198 Initiation, 36, 178, 200 Insertional, 18, 178 Insight, 23, 27, 178

210

Fluconazole

Insulin, 178, 188 Intensive Care, 4, 5, 47, 57, 58, 63, 79, 83, 178 Interferon, 83, 178 Interferon-alpha, 178 Interleukin-1, 30, 178 Interleukin-2, 178 Interleukins, 177, 178 Intermittent, 78, 179 Interstitial, 171, 179, 195 Intestinal, 19, 20, 179 Intestinal Mucosa, 20, 179 Intestines, 153, 170, 172, 173, 179 Intoxication, 179, 203 Intracellular, 20, 34, 43, 50, 105, 106, 177, 179, 182, 191 Intramuscular, 179, 188 Intraocular, 94, 170, 179 Intravenous, 66, 80, 104, 141, 172, 178, 179, 183, 188 Intrinsic, 154, 179 Introns, 173, 179 Invasive, 6, 17, 18, 22, 25, 30, 39, 41, 50, 70, 72, 89, 95, 105, 114, 115, 120, 121, 179 Invertebrates, 11, 179 Ionizing, 154, 179, 194 Ions, 160, 167, 169, 176, 179, 184, 197 Irrigation, 77, 78, 179 Isomerases, 165, 179 K Karyotype, 43, 87, 179 Kb, 134, 179 Keratitis, 77, 176, 179 Ketoconazole, 4, 6, 7, 28, 47, 68, 75, 87, 113, 117, 118, 119, 124, 179 Kinetic, 68, 179 L Labile, 163, 180 Lactation, 48, 70, 180 Large Intestine, 167, 179, 180, 194 Laser therapy, 8, 180 Laxative, 154, 180, 182 Lesion, 158, 180, 199 Leucocyte, 154, 170, 180 Leukaemia, 44, 64, 114, 180 Leukemia, 175, 180, 191 Leukocytes, 43, 83, 158, 159, 161, 178, 180 Leukopenia, 180, 204 Levofloxacin, 58, 180 Lichen Planus, 6, 180 Lidocaine, 180, 183 Life cycle, 11, 172, 180

Linkages, 167, 175, 180, 185, 203 Lipase, 114, 180 Lipid, 66, 78, 103, 178, 180, 183 Liposomal, 37, 66, 69, 70, 181 Liposomes, 100, 181 Liver, 20, 61, 68, 72, 79, 80, 153, 158, 165, 166, 167, 169, 172, 174, 175, 181, 201 Localized, 7, 166, 169, 177, 180, 181, 187, 190 Lovastatin, 100, 181 Low-density lipoprotein, 181 Lumbar, 181, 197 Lumbar puncture, 181, 197 Lymph, 170, 181 Lymphatic, 178, 181, 182 Lymphocyte, 153, 156, 177, 181 Lymphocyte Count, 153, 181 Lymphocyte Depletion, 177, 181 Lymphocytic, 181 Lymphoid, 156, 180, 181 Lymphoma, 102, 175, 181 M Macrophage, 28, 34, 61, 71, 174, 178, 181 Macrophage Colony-Stimulating Factor, 34, 61, 181 Maintenance therapy, 53, 54, 100, 182 Malformation, 74, 182 Malignancy, 55, 86, 182 Malignant, 102, 153, 156, 182, 185, 194 Mannans, 172, 182 Mastoiditis, 120, 182 Maxillary, 120, 182 Maxillary Sinus, 120, 182 Maxillary Sinusitis, 120, 182 Meatus, 182 Mechanical ventilation, 4, 182 MEDLINE, 135, 182 Membrane, 27, 36, 38, 103, 161, 162, 163, 171, 173, 181, 182, 183, 184, 187, 188, 191, 200 Membrane Proteins, 181, 182 Meninges, 140, 161, 164, 168, 182 Mesenchymal, 174, 181, 182 Metabolite, 19, 20, 72, 167, 181, 182, 191 Metastasis, 182, 185 Metastatic, 79, 182 Methylcellulose, 118, 182 Methylene Blue, 41, 80, 183 Methylene Chloride, 118, 183 Mexiletine, 68, 183 MI, 20, 92, 103, 123, 151, 183 Miconazole, 4, 7, 124, 183

211

Microbe, 183, 200 Microdialysis, 64, 183 Microorganism, 160, 162, 183, 188, 203 Microsomal, 19, 183 Microtubules, 183, 187 Midazolam, 20, 183 Mitochondria, 95, 105, 183 Mitosis, 183 Mitotic, 16, 183 Modeling, 15, 26, 183 Modification, 11, 121, 155, 167, 183, 193, 203 Molecular Structure, 184, 201 Molecule, 156, 162, 163, 167, 168, 173, 176, 178, 179, 184, 187, 190, 194, 200, 202 Monitor, 184, 186 Monoclonal, 38, 124, 184, 193 Monocyte, 71, 93, 181, 184 Mononuclear, 181, 184 Morphological, 169, 172, 184 Morphology, 13, 28, 157, 174, 184 Motility, 120, 184, 196 Motion Sickness, 184, 185 Mucins, 166, 184, 195 Mucociliary, 184, 197 Mucocutaneous, 113, 184 Mucosa, 20, 47, 120, 178, 184, 198 Mucositis, 44, 120, 184 Multicenter study, 72, 78, 184 Multidrug resistance, 11, 26, 184 Mutagenesis, 18, 64, 184 Mutagens, 184 Mycological, 42, 184 Mycosis, 50, 115, 184, 187 Mycotic, 10, 29, 93, 95, 112, 113, 184 Myelodysplastic syndrome, 70, 184, 197 Myelogenous, 184 Myocardial Ischemia, 184, 203 Myocardium, 183, 185 Myosin, 159, 185 N Narcotic, 183, 185 Nausea, 140, 185, 188, 201 NCI, 1, 133, 162, 185 Necrosis, 165, 170, 177, 183, 185, 195 Neonatal, 4, 75, 185 Neoplasms, 153, 156, 175, 185, 194 Neoplastic, 181, 185, 195 Nerve, 153, 155, 185, 187, 198, 200, 204 Nervous System, 161, 185, 198, 202 Networks, 11, 185 Neuraminidase, 124, 185

Neurotransmitter, 155, 168, 173, 185, 186, 198 Neutrons, 154, 185, 193 Neutropenia, 58, 115, 121, 172, 186 Neutrophil, 18, 21, 186 Nifedipine, 71, 186 Nitrofurantoin, 80, 186 Nitrogen, 29, 186, 201 Non-nucleoside, 166, 186 Norepinephrine, 153, 155, 168, 185, 186 Nosocomial, 5, 56, 75, 82, 117, 186 Nuclear, 11, 115, 121, 169, 172, 185, 186 Nucleic acid, 165, 167, 184, 186, 195, 203 Nucleus, 158, 162, 165, 166, 172, 184, 186, 192 Nystatin, 4, 6, 7, 37, 44, 51, 66, 78, 112, 123, 124, 186 O Obsessive-Compulsive Disorder, 172, 186 Oligosaccharides, 185, 186 Omeprazole, 187, 192 Oncology, 44, 59, 66, 104, 187 Onychomycosis, 44, 46, 76, 119, 187 Opacity, 166, 187 Opportunistic Infections, 4, 153, 187 Oral Health, 123, 187 Organ Transplantation, 113, 115, 121, 165, 187 Oropharynx, 6, 79, 187 Osteomyelitis, 82, 187 Otitis, 120, 187 Otitis Media, 120, 187 Ovary, 171, 187 Overdose, 172, 187 Overexpress, 17, 187 Ovum, 180, 187, 191 Oxidation, 20, 153, 156, 165, 187 P Pachymeningitis, 182, 187 Paclitaxel, 106, 187 Palate, 187, 198 Palliative, 187, 199 Pancreas, 60, 153, 167, 178, 180, 187, 188 Pancreas Transplant, 60, 188 Pancreas Transplantation, 60, 188 Pancreatic, 114, 188 Panic, 172, 188 Panic Disorder, 172, 188 Parenteral, 4, 188 Parenteral Nutrition, 4, 188 Particle, 188, 200 Pathogen, 16, 17, 22, 23, 24, 25, 177, 188

212

Fluconazole

Pathogenesis, 3, 4, 6, 188 Pathologic, 158, 160, 164, 188 Patient Education, 140, 146, 148, 151, 188 Pelvic, 51, 188 Pelvis, 181, 188, 193, 201 Pepsin, 188 Peptic, 49, 188 Peptic Ulcer, 49, 188 Peptic Ulcer Perforation, 49, 188 Peptide, 42, 155, 169, 188, 190, 192 Perfusion, 189, 200 Peripheral blood, 175, 178, 189, 191 Peritoneum, 189 Peritonitis, 49, 78, 189 Petrolatum, 169, 189 Phagocyte, 181, 189 Phagocytosis, 28, 65, 189 Pharmaceutical Preparations, 161, 171, 189 Pharmacodynamic, 26, 29, 55, 71, 189 Pharmacokinetic, 20, 26, 40, 61, 67, 71, 95, 189 Pharmacologic, 155, 189, 200 Pharynx, 178, 187, 189 Phenolphthalein, 169, 189 Phenotype, 23, 67, 189 Phenyl, 118, 121, 189 Phosphorus, 159, 189 Physical Examination, 8, 189 Physical Therapy, 8, 189 Physiologic, 154, 158, 189, 194 Pigments, 189, 202 Pilot study, 86, 190 Pityriasis, 82, 190 Placenta, 171, 190, 191 Plants, 160, 173, 184, 186, 189, 190, 195, 198, 200, 201, 202 Plaque, 12, 190 Plasma, 26, 27, 41, 42, 60, 61, 63, 70, 86, 156, 161, 190, 194, 200, 203 Plasma cells, 156, 190 Platelets, 190, 196 Ploidy, 16, 190 Pneumonia, 5, 140, 164, 190 Point Mutation, 23, 190 Poisoning, 179, 183, 185, 190 Polyethylene, 118, 190 Polymerase, 157, 190, 195 Polymers, 158, 190, 192 Polymorphic, 41, 87, 190 Polymorphism, 16, 190 Polypeptide, 155, 162, 190

Polyploid, 16, 190 Polyploidy, 16, 190 Polysaccharide, 156, 161, 191 Posterior, 187, 191 Postherpetic Neuralgia, 155, 191 Postoperative, 172, 191 Post-translational, 27, 191 Potassium, 124, 191 Potentiates, 24, 71, 178, 191 Potentiating, 155, 191 Practice Guidelines, 7, 136, 191 Pravastatin, 26, 93, 191 Precursor, 168, 170, 186, 191, 201 Preleukemia, 184, 191, 197 Prevalence, 4, 5, 16, 41, 79, 119, 191 Probe, 183, 191 Progesterone, 191, 198 Progression, 155, 191, 203 Progressive, 19, 166, 168, 185, 192, 195 Proline, 162, 176, 192 Promoter, 12, 26, 27, 39, 192 Promyelocytic leukemia, 66, 192 Prophylaxis, 5, 6, 9, 15, 18, 25, 26, 29, 32, 41, 44, 46, 55, 58, 60, 66, 67, 70, 71, 75, 80, 81, 92, 100, 119, 126, 157, 186, 192, 195 Propolis, 103, 192 Prospective study, 58, 192 Protease, 26, 89, 192 Protease Inhibitors, 26, 89, 192 Protein Binding, 192, 200 Protein C, 155, 157, 173, 192, 201 Protein S, 117, 157, 158, 170, 192 Proteolytic, 154, 163, 192 Proteome, 10, 192 Protocol, 14, 192 Proton Pump Inhibitors, 22, 120, 192 Protons, 154, 176, 179, 192, 193 Proto-Oncogene Proteins, 187, 192, 193 Proto-Oncogene Proteins c-mos, 187, 193 Pruritic, 180, 193, 199 Psychoactive, 193, 203 Public Policy, 135, 193 Publishing, 7, 28, 124, 193 Pulmonary, 18, 77, 80, 159, 174, 175, 193, 195, 202 Pulmonary Artery, 159, 193 Pulmonary Ventilation, 193, 195 Purulent, 170, 193, 202 Pyelonephritis, 32, 35, 36, 193 Pyogenic, 187, 193

213

Q Quality of Health Care, 193, 201 Quality of Life, 11, 193 R Race, 114, 179, 193 Racemic, 114, 193 Radiation, 39, 74, 172, 177, 179, 193, 194, 195, 203 Radiation therapy, 193, 195 Radioactive, 166, 176, 186, 193 Radioimmunotherapy, 193, 194 Radiotherapy, 38, 193, 194 Randomized clinical trial, 6, 84, 194 Reactivation, 18, 194 Receptor, 156, 168, 181, 194, 196 Recombinant, 30, 72, 104, 124, 194, 202 Recombination, 16, 194 Reconstitution, 18, 81, 194 Rectal, 55, 120, 194 Rectum, 157, 159, 167, 171, 172, 180, 194 Recurrence, 24, 194 Reductase, 93, 181, 191, 194 Refer, 1, 159, 163, 172, 175, 186, 194 Reflux, 120, 194 Refraction, 194, 197 Refractory, 84, 86, 92, 104, 194 Regeneration, 194 Regimen, 79, 168, 194 Regurgitation, 174, 194 Relapse, 6, 81, 113, 126, 195 Remission, 182, 194, 195 Renal failure, 54, 195 Renal Replacement Therapy, 54, 195 Respiration, 160, 184, 195 Respirator, 182, 195 Respiratory System, 115, 184, 195 Reverse Transcriptase Inhibitors, 26, 195 Rhabdomyolysis, 82, 195 Rheumatism, 176, 195 Ribavirin, 124, 195 Rifabutin, 35, 72, 195 Rimantadine, 124, 195 Risk factor, 18, 49, 192, 195 S Salicylate, 195, 197 Saliva, 38, 41, 63, 195 Salivary, 165, 166, 167, 195 Salivary glands, 165, 166, 167, 195 Salvage Therapy, 43, 195 Saponins, 195, 198 Sargramostim, 86, 196 Schizoid, 196, 203

Schizophrenia, 196, 203 Schizotypal Personality Disorder, 196, 203 Screening, 15, 30, 31, 52, 162, 196 Sebaceous, 166, 196 Sebaceous gland, 166, 196 Secretion, 164, 179, 180, 184, 187, 196 Sedative, 155, 183, 196 Segregation, 194, 196 Semisynthetic, 171, 196 Sepsis, 114, 172, 196 Septic, 58, 196 Sequencing, 10, 196 Serotonin, 155, 171, 172, 185, 196, 201 Serum, 28, 33, 40, 69, 93, 155, 163, 181, 189, 194, 196 Shock, 58, 75, 196, 201 Side effect, 5, 26, 129, 153, 167, 196, 200 Signs and Symptoms, 195, 196 Sinusitis, 120, 196 Skeletal, 195, 197 Smoldering leukemia, 184, 197 Social Environment, 193, 197 Sodium, 33, 71, 124, 197, 199, 202 Sodium Channels, 197, 202 Sodium salicylate, 33, 197 Soft tissue, 159, 197 Solvent, 11, 116, 158, 171, 183, 197 Somatic, 167, 183, 197 Somatic cells, 167, 183, 197 Specialist, 142, 197 Specificity, 36, 64, 154, 169, 191, 197, 200 Spectroscopic, 11, 197 Spectrum, 18, 114, 115, 118, 121, 124, 162, 179, 197, 203 Sperm, 162, 197 Spinal cord, 140, 141, 161, 162, 168, 182, 185, 187, 197 Spinal tap, 140, 141, 181, 197 Spinous, 170, 197 Spores, 162, 198 Sporotrichosis, 54, 198 Stem Cells, 175, 198 Steroid, 4, 22, 113, 195, 198 Steroid therapy, 4, 113, 198 Stimulus, 198, 199 Stomach, 153, 167, 170, 172, 173, 176, 179, 185, 188, 189, 192, 194, 198 Stomatitis, 12, 102, 198 Stress, 22, 185, 198 Subacute, 120, 178, 196, 198 Subarachnoid, 174, 198 Subclinical, 18, 178, 198

214

Fluconazole

Subcutaneous, 64, 188, 198 Subspecies, 197, 198, 202 Substance P, 170, 182, 194, 196, 198 Substrate, 20, 179, 185, 198 Subungual, 76, 198 Suction, 64, 198 Sulfadiazine, 61, 198 Support group, 8, 198 Suppression, 89, 164, 173, 186, 199, 204 Suppressive, 89, 199 Suspensions, 51, 78, 199, 201 Sweat, 69, 166, 199 Sweat Glands, 166, 199 Symptomatic, 7, 154, 199 Symptomatic treatment, 154, 199 Synergistic, 22, 42, 83, 92, 199 Systemic disease, 176, 199 Systolic, 176, 199, 203 T Tachycardia, 199, 200 Tacrolimus, 54, 83, 199 Talc, 118, 199 Temporal, 174, 182, 199 Testis, 171, 199 Testosterone, 194, 199 Therapeutics, 54, 68, 104, 130, 199 Threshold, 18, 176, 199 Thrombosis, 192, 199 Thrush, 6, 7, 9, 15, 89, 123, 160, 199 Tinea Pedis, 119, 166, 199 Tinnitus, 187, 199 Tissue Distribution, 64, 200 Tolnaftate, 119, 200 Tomography, 40, 200 Topical, 7, 8, 119, 124, 157, 171, 189, 200 Torsades de Pointes, 58, 79, 200 Toxic, iv, 158, 165, 200, 204 Toxicity, 7, 18, 22, 24, 80, 114, 168, 200 Toxicology, 15, 136, 200 Toxins, 156, 169, 170, 177, 194, 200 Transcriptase, 166, 167, 186, 195, 200 Transcription Factors, 12, 200 Transduction, 22, 159, 200 Transfection, 158, 200 Transfusion, 114, 200 Translation, 155, 170, 200 Translational, 25, 173, 200 Translocation, 170, 201 Transplantation, 22, 50, 54, 60, 80, 83, 85, 112, 181, 201 Trauma, 47, 170, 185, 201 Treatment Failure, 12, 26, 201

Trees, 171, 201 Tricyclic, 8, 155, 201 Tryptophan, 162, 196, 201 Tuberculosis, 5, 6, 201 Tunica, 184, 201 U Ulceration, 188, 201 Urea, 199, 201 Uremia, 195, 201 Ureters, 201 Urethra, 201 Urinary, 5, 73, 77, 120, 186, 201 Urinary tract, 5, 77, 120, 186, 201 Urinary tract infection, 77, 186, 201 Urine, 5, 61, 158, 201 Uterus, 191, 201, 202 Uvea, 170, 201 V Vaccines, 201, 203 Vaccinia, 201, 202, 203 Vaccinia Virus, 202, 203 Vagina, 35, 60, 160, 202, 203 Vaginal, 7, 17, 57, 77, 93, 102, 117, 120, 202, 203 Vaginitis, 160, 202 Valganciclovir, 18, 202 Valproic Acid, 61, 202 Varicella, 202, 203 Variegation, 16, 202 Vascular, 166, 174, 177, 178, 190, 202 Vasodilator, 168, 186, 202 Vector, 178, 200, 202 Vegetative, 190, 202 Vein, 179, 186, 202 Venous, 192, 202 Ventilation, 202 Ventricles, 161, 174, 202 Ventricular, 200, 202, 203 Ventricular fibrillation, 200, 202 Venules, 159, 160, 202 Vertebrae, 197, 202 Vertigo, 187, 202 Vesicular, 183, 202 Veterinary Medicine, 135, 203 Vidarabine, 124, 203 Viral, 6, 120, 124, 157, 167, 169, 176, 178, 200, 203, 204 Viral Load, 6, 203 Virulence, 16, 22, 56, 66, 157, 200, 203 Virus Diseases, 157, 203 Vitro, 10, 11, 13, 15, 19, 20, 23, 24, 26, 28, 29, 31, 32, 33, 36, 37, 39, 41, 42, 47, 48,

215

50, 51, 65, 66, 68, 87, 88, 93, 94, 95, 102, 103, 104, 105, 114, 177, 199, 203 Vivo, 11, 19, 20, 21, 26, 39, 41, 114, 181, 203 Voriconazole, 28, 32, 33, 35, 36, 39, 45, 51, 57, 62, 65, 68, 81, 87, 95, 120, 203 Vulva, 203 Vulvovaginitis, 8, 50, 88, 203 W War, 4, 161, 203 White blood cell, 156, 162, 174, 180, 181, 184, 186, 190, 203

Withdrawal, 71, 89, 203 X Xamoterol, 54, 203 Xenograft, 156, 203 X-ray, 11, 172, 186, 193, 194, 203 Y Yeasts, 12, 30, 65, 67, 82, 89, 94, 101, 160, 172, 189, 203 Z Zidovudine, 61, 203 Zoster, 175, 203, 204

216

Fluconazole