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

THALIDOMIDE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

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THALIDOMIDE 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., 1960Thalidomide: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84653-7 1. Thalidomide-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 thalidomide. 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 THALIDOMIDE........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Thalidomide................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 32 The National Library of Medicine: PubMed ................................................................................ 33 CHAPTER 2. NUTRITION AND THALIDOMIDE ................................................................................. 79 Overview...................................................................................................................................... 79 Finding Nutrition Studies on Thalidomide ................................................................................. 79 Federal Resources on Nutrition ................................................................................................... 82 Additional Web Resources ........................................................................................................... 82 CHAPTER 3. ALTERNATIVE MEDICINE AND THALIDOMIDE .......................................................... 85 Overview...................................................................................................................................... 85 National Center for Complementary and Alternative Medicine.................................................. 85 Additional Web Resources ........................................................................................................... 90 General References ....................................................................................................................... 91 CHAPTER 4. DISSERTATIONS ON THALIDOMIDE ............................................................................ 93 Overview...................................................................................................................................... 93 Dissertations on Thalidomide ...................................................................................................... 93 Keeping Current .......................................................................................................................... 93 CHAPTER 5. PATENTS ON THALIDOMIDE ....................................................................................... 95 Overview...................................................................................................................................... 95 Patents on Thalidomide................................................................................................................ 95 Patent Applications on Thalidomide.......................................................................................... 105 Keeping Current ........................................................................................................................ 113 CHAPTER 6. BOOKS ON THALIDOMIDE ......................................................................................... 115 Overview.................................................................................................................................... 115 Book Summaries: Online Booksellers......................................................................................... 115 The National Library of Medicine Book Index ........................................................................... 116 Chapters on Thalidomide ........................................................................................................... 117 CHAPTER 7. PERIODICALS AND NEWS ON THALIDOMIDE ........................................................... 121 Overview.................................................................................................................................... 121 News Services and Press Releases.............................................................................................. 121 Newsletter Articles .................................................................................................................... 126 Academic Periodicals covering Thalidomide.............................................................................. 126 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 The Genome Project and Thalidomide ....................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 141 Overview.................................................................................................................................... 141 Patient Guideline Sources.......................................................................................................... 141 Finding Associations.................................................................................................................. 144 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 147

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Overview.................................................................................................................................... 147 Preparation................................................................................................................................. 147 Finding a Local Medical Library................................................................................................ 147 Medical Libraries in the U.S. and Canada ................................................................................. 147 ONLINE GLOSSARIES................................................................................................................ 153 Online Dictionary Directories ................................................................................................... 153 THALIDOMIDE DICTIONARY ................................................................................................ 155 INDEX .............................................................................................................................................. 227

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

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

Thalidomide for the Treatment of Oral Aphthous Ulcers in Patients with Human Immunodeficiency Virus Infection Source: New England Journal of Medicine. 336(21): 1487-1493. May 22, 1997. Summary: In patients with advanced HIV infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. This article reports on a doubleblind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Sixteen of the 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent). Pain diminished and the ability to eat improved with

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thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each) and 6 of the 29 patients discontinued treatment because of toxicity. The authors conclude that thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection. 2 figures. 2 tables. 43 references. (AA-M). •

Thalidomide in the Treatment of the Mucocutaneous Lesions of the Behcet Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial Source: Annals of Internal Medicine. 128(6): 443-450. March 15, 1998. Summary: Recurrent oral and genital ulcers are the most frequent problem in the management of the Behcet syndrome. Uncontrolled experience suggests that thalidomide may help prevent recurrences of these ulcers. This article reports on a double blind, placebo controlled study undertaken to determine the efficacy of two thalidomide dosages in the treatment of mucocutaneous lesions of the Behcet syndrome. The study population was 96 male patients with the Behcet syndrome who primarily had mucocutaneous lesions without major organ involvement. The intervention was thalidomide, 100 mg per day, or 300 mg per day, or placebo for 24 weeks. Outcome measures were sustained absence of any oral and genital ulceration during treatment (complete response) and changes in the number of mucocutaneous lesions. An additional evaluation was done 4 weeks after treatment ended. A complete response occurred in 2 of the 32 patients (6 percent) receiving 100 mg per day of thalidomide; in 5 of the 31 patients (16 percent) receiving 300 mg per day of thalidomide; and in none of the 32 patients (0 percent) receiving placebo. The suppressive effects of thalidomide with either dosage was evident at 4 weeks for oral ulcers and at 8 weeks for genital ulcers and follicular lesions. This effect persisted during treatment but diminished rapidly after treatment was discontinued. Both thalidomide dosages led to significant increases in the number of erythema nodosum lesions during the first 8 weeks of treatment. Polyneuropathy developed in 4 patients; in 3 of these patients, the condition was diagnosed after the trial had ended. The authors conclude that thalidomide is effective for treating the oral and genital ulcers and follicular lesions of the Behcet syndrome. A dosage of 100 mg per day is as effective as a dosage of 300 mg per day. 3 figures. 3 tables. 25 references.

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Thalidomide in the Treatment of the Mucocutaneous Lesions of the Behcet's Syndrome Source: Annals of Internal Medicine. 128(6):443-450. March 15, 1998. Summary: This journal article for health professionals describes a randomized, doubleblind clinical trial conducted to determine whether thalidomide is an effective treatment of the mucocutaneous lesions of Behcet's syndrome. Participants were 96 male patients who were 18 to 35 years old and met international criteria. For the 24-week period, they received 100 or 300 milligrams of thalidomide or a placebo daily. Statistical analysis was conducted on 95 patients because 1 patient in the 300 milligram/day group withdrew. The primary outcome measure was the absence of any oral or genital ulcer of any size during the treatment period. Results reveal that there were no lesions in 2 of the 32 patients receiving the 100 milligram/day dose of thalidomide, in 5 of the 31 patients receiving the 300 milligram/day dose, and in none of the 32 patients receiving placebo. The suppressive effect of either dose of thalidomide was evident at 4 weeks for oral ulcers and at 8 weeks for genital ulcers and follicular lesions. This effect persisted during treatment but diminished rapidly after it was discontinued. Both dosages led to significant increases in the number of erythema nodosum lesions during the first 8

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weeks of treatment. Polyneuropathy developed in 1 patient in the 100 milligram/day group and in 3 patients in the 300 milligram/day group. In 3 of these patients, the condition was diagnosed after the trial ended. The article concludes that thalidomide is effective for treating the oral and genital ulcers and follicular lesions of Behcet syndrome. Efficacy seemed to be similar at both dosages. 3 figures, 3 tables, and 25 references. (AA-M). •

Effective Treatment of Oral Erosive Lichen Planus With Thalidomide Source: Archives of Dermatology. 136(12): 1442-1443. December 2000. Summary: This journal article uses a case report to provide health professionals with information on the treatment of oral erosive lichen planus with thalidomide. The case involves a 70 year old man with a 2 year history of bloody gums and fetid breath. Treatment with topical corticosteroids, oral prednisone, and immunosuppressive agents failed to produce lasting clinical improvement. His current medication was cyclophosphamide. When thalidomide became available in 1998, doctors prescribed it for the man at a starting dosage of 50 milligrams per day for 2 weeks. This was gradually increased over 3 months to 200 milligrams per day. All other therapy was discontinued. Dosage had be deceased to 100 milligrams per day to reduce side effects to a tolerable level. After 4 months of treatment, the man reported a decrease in pain, redness, bleeding with brushing, and fetid breath. Treatment was discontinued after 1 year 5 months, but about 2 weeks after treatment cessation, the man reported gum pain. The article discusses the effectiveness of thalidomide as a treatment for lichen planus, highlights its adverse effects, and explains how the drug is distributed. 2 figures and 4 references.

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

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

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Project Title: ACTG--267 PHARMACOKINETICS SUBJECTS WITH HIV-1 INFECTION

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Principal Investigator & Institution: Van Der Horst, Charles M.; Medical Director; 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 •

Project Title: AIDS DIARRHEA: SYMPTOM & CYTOKINE RESPONSE TO THALIDOMIDE TREATMENT Principal Investigator & Institution: Basuk, Paul; Weill Medical College of Cornell Univ New York, Ny 10021 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: ANABOLIC THERAPIES AND THEIR METABOLIC EFFECTS IN AIDS Principal Investigator & Institution: Schambelan, Morris; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-MAY-2004 Summary: The major goals of this project are: 1) To investigate the mechanisms underlying the anabolic effects of thalidomide, 2) To determine the dose of hGH which achieves the optimal anabolic effect, 3) To determine whether a combination and thalidomide act synergistically to improve the functional lean body mass (LBM). The applicant proposes that administration of a lower doses of hGH may avoid the metabolic and structural side effects of hGH and combination with thalidomide may be additive or synergistic. He proposes to study the effects of these two agents under metabolic ward conditions, using metabolic balance studies, whole body kinetic studies, direct determination of muscle protein synthesis, and body fluid compartments. The specific aims are: 1) to find an optimal dose of hGH which will achieve the proteinanabolic effects without causing (or minimizing), the hypermetabolism and accumulation of non-functional extracellular tissue. 2) to determine whether thalidomide decreases the net protein degradation without increasing lipid oxidation and REE. 3) to test whether administration of thalidomide in combination with lower doses of hGH achieve a selective increase in the functional, as opposed to nonfunctional, lean tissue and causes a smaller increase in the REE. Total number of 42 HIV+ patients and HIV- control subjects will be included over a period of 5 years. All subjects will participate in a 2 week inpatient study, which will involve treatments with hGH or thalidomide or both. Then the HIV+ patients will continue their treatments for another 10 weeks. At the end of these period HIV+ patients will be readmitted for a 5 day period for the repeat studies. The investigations will include 1) the measurements of body weight and composition (by DEXA, bioelectrical impedance, D20 and Na bromide dilution, and midarm circumference measurement techniques), 2) metabolic balance studies of nitrogen, K, Na, SO4, 3) determination of resting energy expenditure and substrate oxidation rates by indirect calorimetry, 4) protein and lipid metabolism studies using stable isotopes of leucine and glycerol, 5) determination of muscle protein

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synthesis by measuring the incorporation of leucine to muscle protein and abundance of myosin heavy chain mRNA, 6) measurements of hormones, metabolites, TNFalpha and other cytokines, immunologic and virologic parameters. This study will address the mechanisms of HIV-induced wasting and investigate the role of two potential medical treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANGIOGENESIS AND THALIDOMIDE THERAPY IN MULTIPLE MYELOMA Principal Investigator & Institution: Rajkumar, S Vincent.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (Provided by applicant): Angiogenesis is increased in multiple myeloma (MM) and has prognostic value. The anti-angiogenic agent, thalidomide, is effective in refractory MM and has shown marked synergy with dexamethasone. A randomized multi-institutional ECOG study will compare thalidomide plus dexamethasone versus dexamethasone alone in newly diagnosed MM. This proposal will utilize blood and bone marrow (BM) samples from this important study to test the central hypothesis that angiogenesis is important in MM and that anti-angiogenic therapy will be an effective way to treat MM. Preliminary data indicate that thalidomide can lead to decreased BM angiogenesis and VEGF expression. We hypothesize that thalidomide decreases the expression of VEGF and its receptors and inhibits BM angiogenesis, resulting in increased plasma cell apoptosis, decreased proliferation and tumor response. We also have data that support our hypothesis that thalidomide plus dexamethasone can inhibit mesenchymal progenitor cell (MPC) cytokine expression and differentiation. The proposal is organized into 3 specific aims: 1) To compare changes in BM angiogenesis and the level of expression of VEGF and its receptors before and after therapy and to correlate these measurements with response to therapy. 2) To determine the relationship between BM angiogenesis and MM cell VEGF expression with rates of myeloma cell apoptosis and proliferation and 3) To determine if thalidomide therapy inhibits expression of angiogenic cytokines/growth factors by BM MPC's and restores normal BM MPC function. For all 3 aims, our hypothesis is that the effects will be more pronounced with thalidomide plus dexamethasone than with dexamethasone alone. BM angiogenesis will be studied using immunohistochemical staining for CD34 and the rat aortic ring assay. Immunohistochemistry, in-situ hybridization, ELISA and RT-PCR assays will be used for the study of VEGF and its receptors and MPC cytokine expression. MPC growth and differentiation will be studied and compared to normal controls. Apoptosis will be measured using flow cytometric assays that gate on tumor cells; plasma cells in S-phase and circulating plasma cells will be estimated using slide based immunofluorescent assays. This study offers a unique opportunity to serially study tumor cells and the tumor microenvironment following potential anti-angiogenic therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANGIOGENESIS IN B CHRONIC LYMPHOCYTIC LEUKEMIA Principal Investigator & Institution: Kay, Neil E.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2004

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Summary: (Adapted from the investigator's abstract) B-Chronic Lymphocytic Leukemia (B-CLL) is a clonal B cell disorder that represents the most common leukemia in North America. We have also recently determined that abnormal angiogenesis (blood vessel formation) exists in the marrows of patients with B-CLL. Importantly, we have also determined that circulating clonal B cells and T cells contain specific cytokines/vascular growth factors that may mediate this abnormal angiogenesis. Our hypothesis is that these immune cells produce and secrete factors that are critical in the induction and maintenance of abnormal angiogenesis and B-CLL. Since angiogenesis has now been shown to be necessary for solid tumor growth and metastatic potential, the same may be true for this common human B cell malignancy. Therefore, we intend to study B-CLL patients entering onto an NCCTG clinical trial using oral thalidomide, an agent with potential anti-angiogenic activity to determine if these patients respond to this therapy and if this response is associated with changes in the angiogenic activity seen in B-CLL. In specific, we will evaluate the association of blood, urine and clonal B cell synthesized proteins that have either pro angiogenic or anti-angiogenic growth factor potential with the abnormal angiogenic marrow patterns in B-CLL. We will also determine if the CLL B cell secreted products can directly stimulate human vascular tissue. We believe that that this approach will allow us to determine the relationship/association of biologic parameters in B-CLL that mediate the abnormal blood vessel patterns known to be present in B-CLL patients. We may identify CLL patients who respond to thalidomide with repair of the abnormal angiogenic patterns and reduction in the cellular production and secretion of angiogenic growth factors. This latter finding would strongly suggest that maneuvers to alter the angiogenic potential in B-CLL patients would be an important and novel therapeutic approach in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANN ARBOR REGIONAL CCOP Principal Investigator & Institution: Stella, Philip J.; Catherine Mc Auley Health Center Box 992, 5301 E Huron River Dr Ann Arbor, Mi 48106 Timing: Fiscal Year 2002; Project Start 05-AUG-1994; Project End 31-MAY-2007 Summary: (provided by applicant): The mission of the Ann Arbor Regional CCOP (AARCCOP) is to improve the oncologic health of the communities served by assuring patient access to and participation in state-of-the-art clinical trials and cancer prevention and control activities while contributing to knowledge development in the field of oncology care. The AARCCOP represents a proven resource with significant potential to serve the objectives of the National Cancer Institute?s CCOP program. First funded in 1994 as a single component CCOP with total annual accrual of 100 patients to treatment and cancer control trials, it now is comprised of seven component institutions with annual accrual of 250+ patients. The AARCCOP has worked thoughtfully and diligently to achieve the phenomenal growth experienced over a short seven-year period. This grant application encompasses and articulates an ever-expanding vision for the AARCCOP. To more accurately reflect and facilitate the AARCCOP?s growth strategies for the future, its name will change to the Michigan Cancer Research Consortium in Fall 2001. Not only does this name suggest a broader catchment area, but it supports the CCOP?s growing participation in translational research, the development of systems to recruit and engage physicians as investigators, continued work with professional organizations and third-party payers to expand funding, and implementation of methods to access and execute RO-l-funded clinical trials. Strategic initiatives to increase accrual and minority participation in clinical trials are delineated and provide the framework for our work. Of importance during this upcoming grant cycle will be the

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AARCCOP?s continued focus on improving the efficiency and cost-effectiveness of participation in clinical trials through expansion of its custom data management software system to include both a drug inventory management module and an IRB module. Key to streamlining CCOP operations will be the early development of the AARCCOP?s website; this will allow component sites to easily access information online. The AARCCOP is confident these goals will be accomplished because of the commitment and belief by investigators and staff that what they do is critically important for present and future oncologic care. Convinced that our patients are better served by the availability of a strong, quality-oriented, community research program, the Ann Arbor Regional CCOP is committed to being one of the most successful CCOPs in the country, contributing significantly to oncology clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI TNF ALPHA ACTIVITY OF THALIDOMIDE IN TNF ALPHA ARTHRITIS Principal Investigator & Institution: Taylor, Laventrice D.; Morgan State University Baltimore, Md 21251 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: CE-MS OF BIOLOGICAL SUBSTANCES USING CHIRAL POLYMERS Principal Investigator & Institution: Shamsi, Shahab A.; Chemistry; Georgia State University University Plaza Atlanta, Ga 30303 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: In many health related fields the resolution and structural identification of enantiomeric compounds are necessary steps for studying racemic drug interactions. The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) using conventional micelles [above the critical micelle concentration (CMC)] is very difficult if not impossible. Preliminary data in our laboratory indicates that the uses of polymerized surfactant or micelle polymers provide one possible solution for this difficult coupling. This is because of many positive attributes of micelle polymers which includes zero CMC, lower surface activity, low volatility and function as suitable separation media even at lower concentrations of pseudophases. These are some benefits that produce a stable electrospray. This proposal is aimed at synthesis and development of new class of chiral anionic and cationic micelle polymers for use in chiral electrokinetic chromatography (EKC)-MS. Depending on the polarity of the chiral analytes two different approaches are proposed for the success of chiral EKC-MS. The first approach involves simply the use of chiral micelle polymers as additives in EKCMS or partial-filling EKC-MS for the separation of very polar and charged compounds. For the chiral separation and MS detection of very hydrophobic and neutral chiral molecules that have large capacity factors and low ionization efficiency, a second approach is proposed. This involves the use metal complexes of anionic micelle polymers as reagents for the coupling of ligand exchange-EKC to coordination ion mass spectrometry. The combined use of metal with chiral micelle polymers will not only provide faster and efficient chiral separations of hydrophobic molecules but will also help in efficient transport of complexes to the gas phase for electrospray ionization. In addition, a dual chiral selector system, capillary electrochromatography (CEC)-EKC-MS is also proposed for analytes with multiple chiral centers. Following studies on the

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optimization of chiral EKC-MS of wide variety of chiral compounds, two different methods will be developed to improve the concentration sensitivity of CE-MS. The first methodology includes a new approach in developing an automated capillary isotachophoresis in conjunction with chiral EKC to improve the sample loadability of the chiral analytes which will benefit analysis of chiral metabolites at therapeutic levels without sample preparation. Besides this, a second methodology involves investigation on chiral EKC-MS-MS for trace level detection and understanding of the metabolic pathways of patients undergoing warfarin and thalidomide therapy for various diseases. We realize that the application of this valuable technology of chiral EKC-MS and chiral EKC-MS-MS will lead to the significant advances across several scientific disciplines. The strategies described in this proposal may signal a new beginning of a highly efficient and information rich hyphenated technology, which will enable our research group and others to acquire significant high throughput screening methods for analysis of chiral drugs than ever previously experienced. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPASSIONATE USE OF THALIDOMIDE IN ADULTS WITH HIV ASSOCIATED WASTING Principal Investigator & Institution: Abrams, Donald; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--PHARMACOLOGY Principal Investigator & Institution: Dorr, Robert T.; Professor of Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: Description (provided by applicant) The pharmacology core service will provide several levels of service each project. These services include (1) the development, or adaptation of existing analytical procedures for detecting novel compounds in biological matrices; (2) the application of these procedures to blood, tumor and surrogate tissues such as peripheral blood white blood cells; (3) the mathematical description of the pharmacokinetics of each novel agent; and most importantly, (4) the development of pharmacodynamic correlations of each agent s pharmacokinetic disposition with biologic outcomes, including antitumor response and perturbation of the specific molecular target. To accomplish these goals, the service will utilize established high performance liquid chromatographic (1- IPLC) assays for analyzing novel inhibitors of l) VEGF in Project 2 (thalidomide and SU-5416; (2) heat shock protein-90 in Project 3 (17-AA-gledanamycin and chlorobiocin). For Project 1, anew gas chromatographic assay will be developed for the signal transduction inhibitor DPIEL. An existing radiolabeled wortmanin assay will be used for detecting this agent in Project 1. The data on plasma and tumor levels of these agents will be analyzed by non-compartmental methods to derive standard pharmacokinetic indices, and most importantly, the area under the plasma (or tumor) concentration x time curve, (AUC), in the tumor-bearing rodent models. Pharmacodynamic correlations will be performed for these pharmacokinetic parameters with, (1) the inhibition of Tumor growth and (2), the degree of perturbation of the molecular target. This will facilitate the overall goal of describing target AUCs which will need to be achieved in human trials of each agent,

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and the degree of target inhibition achieved by different doses and schedules of each novel agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOKINE INHIBITION IN HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Schwartz, Jonathan D.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: (provided by applicant): The candidate is a Clinical Assistant Professor in the divisions of Medical Oncology and Hematology in the Department of Medicine at The Mount Sinai School of Medicine. He is also Co-Director of the Hematology-Oncology Fellowship. He will pursue career development in the responsible conduct of clinical research while planning and conducting preliminary trials and translational research for patients with unresectable hepatocellular carcinoma. The plans for career development include participation in research methodology courses through the institution's K30 award (Principal Investigator, Janice Gabrilove, M.D., Division Chief in Medical Oncology), ongoing participation in clinical investigation, multi disciplinary care of patients with liver diseases and hepatobiliary malignancies, and mentorship by faculty with proven investigative and training capabilities in Clinical Oncology, Liver Diseases, and translational research (including Janice Gabrilove, M.D., Scott Friedman, M.D.). The cytokines basic fibroblast growth factor (bFGF), insulin-like growth factor II (IGF-II), transforming growth factor-alpha (TGF-alpha), vascular endothelial growth factor (VEGF) and the process of neoangiogenesis have been shown to play a critical role in the pathogenesis of hepatocellular carcinoma. Outlined in this application, the research plan is based upon the hypothesis that inhibition of cytokine-mediated tumor cell survival and growth, and inhibition of neoangiogenesis, are likely to be of clinical utility. Inhibitors of specific cytokines and their receptors are currently available for evaluation as therapeutic agents for this disease in which these specific biological processes have been shown to play a critical role in pathogenesis, evolution and progression. Given the institutional strength as a center of excellence in liver disease and liver transplantation, the support of outstanding mentors, strong institutional resources for clinical investigation, an intense didactic curriculum in clinical research, and the candidate's potential for developing multi disciplinary clinical research, it is highly likely that the five-year training period will enable the candidate to emerge as an innovative, disciplined clinical and translational investigator, with a focus on the development of novel therapeutic strategies in hepatobiliary malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOKINES IN PATHOGENESIS OF ANTHRAX INFECTION Principal Investigator & Institution: Kaplan, Gilla; Full Member; Public Health Research Institute 225 Warren St Newark, Nj 071033535 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Death from systemic anthrax in humans results from massive inflammation, multi-organ failure and shock caused by harmful levels of Bacillus anthracis exotoxins. Early antibiotic treatment can improve survival by eliminating infectious organisms, however, most victims succumb because antibiotics are administered too late in the course of anthrax infection when toxins have already reached critically high levels. It is our hypothesis that, in addition to the direct effects of the anthrax toxins, specific proinflammatory cytokines produced in response to

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infection with B. anthracis contribute significantly to the pathogenesis of systemic disease. In our proposed study, we will define the proinflammatory cytokine cascade in B. anthracis-infected monocytes in vitro, in mice infected by inhalation of B. anthracis and in rabbits with anthrax meningitis. We will investigate whether inhibition of the production of specific proinflammatory cytokines improves outcome in these animal models of B. anthracis infection and treatment. In particular, we will study the effects of antibiotics combined with immunomodulatory drugs (thalidomide analogues) on the pathogenesis of anthrax meningitis, reported in 50% of human cases of systemic anthrax and associated with long term CNS damage and impaired cognitive functions in survivors of this condition. We have access to suitable BL3 facilities, experience in working with virulent clinical isolates of Mycobacterium tuberculosis both in vitro (in cultured fresh human monocytes) and in vivo (in mouse and rabbit models of infection), and access to novel immunomodulatory drugs (thalidomide analogues). Thus we are in a unique position to conduct the proposed studies. We believe that an improved understanding of the cytokine cascade which may be exacerbated by products released from bacilli killed by antibiotic treatment, and better insight into the contribution of cytokines to the pathology of anthrax will enable the design of superior treatment regimens as clinical countermeasures using antibiotics supplemented by selected immunomodulatory drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT EDUCATIONAL MEDIA

OF

TERATOGENIC

SYMBOLS

AND

Principal Investigator & Institution: Goldsworthy, Richard; Director, R&d; Academic Edge, Inc. 216 W Allen St, Ste 143 Bloomington, in 47403 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 01-MAR-2004 Summary: (provided by investigator): The prescription of pharmaceuticals with teratogenic properties has increased rapidly over the past decade with the heightened popularity of Accutane, the renewed use of Thalidomide for its antiangiogenic characteristics, and the growth in use of other birth-defect inducing drugs. With this increase comes a concomitant increase in the risk of women of child-bearing age being or becoming pregnant while taking a potentially teratogenic pharmaceutical. A recent study indicates that women frequently misinterpret a commonly used warning label, especially in the absence of instruction or educational materials. Since instruction is often frequently omitted in pharmacist-patient and physician-patient interaction, the warning label is a first and central intervention. High sensation seeking individuals are at heightened risk for overlooking or ignoring symbols and warnings yet evidence exists that messages designed specifically for HSS individuals are successful and, moreover, still work with the general population. There is, therefore, an urgent need for symbols and media that convey the danger of taking teratogenic pharmaceuticals while pregnant or preconception in a clear, unambiguous manner or, at worst, that lead to no harmful misinterpretations or misconceptions. Media designed for HSS individuals should be particularly valuable In Phase I of this project, AEI will work closely with graphic designers, researchers, and evaluators, to create a series of symbols and warnings (symbols plus text) that communicate the teratogenic properties of a substance. These symbols will be developed formatively using an iterative design and working closely with target audience members. The final prototype symbol(s) and warning(s) will be evaluated in a large-scale (n=400) study implementing a one-on-one interview protocol that will draw from diverse geographic locations in order to ensure cultural, racial, ethnic, and regional utility. With the prototype symbols developed and evaluated in

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Phase I, Phase II will create a series of educational media modules to increase awareness of the symbols and warnings and to educate professionals and the public on teratogenicity. These materials will include a reference web-site, a set of brochures for pharmacies and practitioners, small media materials (such as posters) for display, and a video documentary. All materials will be delivered in both English and Spanish. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL THERAPEUTICS Principal Investigator & Institution: Munshi, Nikhil C.; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002 Summary: (Applicant's Description) Myeloma cells are associated with complex karyotypic abnormalities leading to a multiplicity of antiapoptotic mechanisms that are additionally supported by autocrine and paracrine loops, exercised in concert with the tumor microenvironment. In the last 4 years, we have reported on the efficacy of highdose therapy, the grave prognostic significance of cytogenetic changes, and the role of combination chemotherapy and thalidomide in patients who have relapsed after transplantation. Also, we have demonstrated the therapeutic benefit of immune-based therapy. Based on these results, we hypothesize that a curative strategy for myeloma requires multi-agent therapy directed at both tumor cells and accessory elements that support myeloma cell growth. Our goal is to develop new and improved therapies, including cytotoxics, immunotherapy (idiotype or dendritic cell vaccination, donor lymphocyte infusions), antiangiogenic therapy (thalidomide), antistromal cell treatments (bisphosphonates), and assess newer agents in previously treated patients. To achieve this goal, the following aims will be pursued. Specific Aim 1: Compare the efficacy of multi-agent angiochemotherapy (DT-PACE) with that of tandem transplant with high-dose single-agent chemotherapy (melphalan) in a randomized phase III clinical trial for previously treated patients. The rationale is to evaluate whether patients will have superior response to multi-agent chemotherapy when compared with singleagent high-dose therapy. Specific Aim 2: Evaluate the role of immunological approaches in achieving or maintaining CR or partial remission (PR). Patients achieving CR/PR status will be enrolled on one of the currently ongoing idiotype (UARK-94-008) and dendritic cell vaccination protocols (UARK-96-023) to investigate clinical humoral and cellular responses. Additionally, patients with inadequate response or relapse will undergo "micro-allotransplants" or receive tumor-specific cytotoxic T lymphocytes. Specific Aim 3: Evaluate novel agents or their combinations in phase II studies in resistant or relapsing patients. The proposed, investigator-initiated clinical studies are likely to provide answers to important questions regarding the novel therapeutic approaches directed at various molecular targets and to provide information regarding the role of single-agent high-dose chemotherapy in MM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY CYSTEINE:CONCEPTAL RESPONSE TO OXIDATIVE STRESS Principal Investigator & Institution: Harris, Craig; Associate Professor of Toxicology; Environmental Health Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 30-APR-2004

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Summary: (provided by applicant) Adequate dietary intake of thiol amino acids has been implicated as an important factor in the ability to withstand chemical and environmental insults that elicit oxidative stress. Without adequate free cysteine, the ability to restore glutathione that is lost due to oxidation is compromised by inadequate glutathione synthesis where sensitive target cells and tissues are damaged or killed due to the consequences of unresolved oxidative stress. The mechanisms of some important human diseases and adverse health conditions (e.g., HIV, malnutrition, inflammation) have been directly linked to low systemic glutathione, secondary to decreases in cysteine availability. Similar consequences of depleted and/or oxidized glutathione, leading to exacerbation of embryotoxicity and increased frequency and severity of teratogenic lesions, have been reported. Several human teratogens are known to elicit oxidative stress, although relatively little is known about the mechanisms that regulate antioxidant activity in the conceptus. Demonstrated differences in the rates of new glutathione synthesis in the developing embryo and its extra-embryonic membranes suggest that the availability of free cysteine, as the rate-limiting precursor for new glutathione synthesis, might be important for the determination of selectivity or resistance to chemical embryotoxicants. The investigators hypothesize that the availability of free cysteine in the embryo and visceral yolk sac of the post-implantation embryo determines the extent to which the embryo is able to maintain adequate glutathione concentrations and respond to chemically-induced oxidative stress by synthesizing new glutathione for restoration of normal redox status. Preliminary experiments with chemical embryotoxins, such as the pesticides lindane and aminocarb, show selective decreases in free cysteine concentrations prior to observed depletion of glutathione and onset of toxicity. Interspecies comparisons between the rat and rabbit show significant reductions in tissue glutathione and cysteine in the rabbit that may help explain the greater sensitivity of the rabbit to teratogens that produce oxidative stress such as thalidomide. The investigators propose to compare glutathione/glutathione disulfide/cysteine status and rates of new glutathione synthesis between rat and rabbit conceptual tissues. They will assess the effects of lindane and aminocarb on these endpoints and determine whether mechanistic relationships exist between a species' or tissue's ability to obtain cysteine and synthesize new glutathione and specific cell sensitivity or resistance to toxic chemicals. Whole animal, whole embryo culture and cell cultures (micromass limb/midbrain and spinal neural crest) will used to assess the role of cysteine in embryoprotection. In vitro and in vivo experiments will determine whether dietary restriction of cysteine differentially exacerbates toxicity in the two species and/or whether dietary or direct supplementation of cysteine is adequate to protect the embryo from chemical insult. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF THALIDOMIDE ON INSULIN ACTION & GLYCEMIC CONTROL Principal Investigator & Institution: Boden, Guenther; Temple University 406 Usb, 08345 Philadelphia, Pa 19122 Timing: Fiscal Year 2002 Summary: Tumor necrosis factor alpha (TNF-alpha) is known to produce insulin resistance. The objective of this investigator-initiated study is to demonstrate the effects of inhibition of TNF-alpha synthesis on insulin resistance in obese type 2 diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE METHYLATION AND THERAPEUTIC RESPONSE IN LUNG CANCER Principal Investigator & Institution: Belinsky, Steven A.; Director Lung Cancer Program; Lovelace Biomedical & Environmental Res Albuquerque, Nm 87108 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: Lung cancer is responsible for approximately one-third of all cancer-related deaths in the U.S. each year. Chemotherapy has been largely ineffective in producing complete responses or cures in the advanced disease setting. Therefore, investigation of new paradigms, including novel therapeutic approaches and early detection, has become an urgent priority for the oncology community. Key to early detection is the development of biomarkers that are found in primary tumor and can be detected in biological fluids prior to advanced disease. These biomarkers may also be useful for predicting therapeutic response during clinical trials. In support of these critical needs, our laboratory has identified two excellent biomarkers, the p16 tumor suppressor gene and the O6-methylguanine-DNA methyltransferase (MGMT) repair gene, whose inactivations through aberrant CpG island promoter hypermethylation occur frequently and early in the development of NSCLC. Furthermore, inactivation of these genes has been detected in exfoliated cells from sputum and shown to precede clinical diagnosis of squamous cell carcinoma (SCC). Aberrant methylation of p16, MGMT, and deathassociated protein (DAP) kinase has also been detected in serum from NSCLC patients irrespective of tumor stage. Utilizing specimens and patients on ECOG study E3598, "A Phase III trial of Carboplatin, Paclitaxel and Radiotherapy, With or Without Thalidomide, in Patients With Stage III NSCLC," these advances in cancer biology will be translated into the clinic to address several important questions. First, can the detection of gene dysfunction in critical genes through analysis of sputum and/or serum be used for screening or as prognostic factors? This question will be addressed by determining the predictive power of sputum and serum to detect NSCLC through analysis for aberrant methylation of the p16, MGMT, DAP-kinase, and TIMP-3 genes within these biological fluids. Second, does inactivation of genes such as p16, DAPkinase, or TIMP-3 in NSCLCs affect survival? A recent study demonstrated that median survival was shorter for patients with adenocarcinoma in which the p16 gene was inactivated. Thus, this question will be addressed by determining whether inactivation of p16, DAP-kinase, or TIMP-3 genes can be used to predict survival for patients on E3598. Finally, can detection of methylation markers in serum be useful for cancer diagnosis and/or have predictive value for survival? This will be addressed with patients on E3598. Results could have a profound impact on defining the utility of sputum and serum for detecting NSCLC, predicting survival from these therapeutic regimens, and delineating whether the presence of these tumor markers in serum affect survival. The validation of these genes as biomarkers of lung cancer risk and their detection in sputum and/or serum could ultimately support chemoprevention trials for preventing lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENOTYPE AND PHENOTYPE OF BRAINSTEM INJURY IN AUTISM Principal Investigator & Institution: Rodier, Patricia M.; Professor; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-AUG-1998; Project End 31-MAY-2008 Summary: (provided by applicant): Autism is a neuro-developmental disorder with several known environmental and genetic risk factors. Converging evidence from

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anatomical studies, teratologic studies, and studies of comorbid conditions suggest that one cause of autism is early maldevelopment of the brain stem. Evidence for several new candidate genes for ASD susceptibility has been published in the last year, and all are genes involved in the embryonic development of the brain stem. In Project I, Animal Models of Autism and Mechanisms of Injury, the investigators will study the neuroanatomy of animal models and quantify gene expression in embryos exposed to teratogens, using real-time PCR and in situ hybridization. They propose to extend out studies of the mechanisms of action of teratogens associated with autism to investigate the role of histone deacetylation. The investigators will compare transcription efficacy of polymorphisms of genetic susceptibility factors in TET-responsive cell lines, and look for gene-environment interactions in genetically-engineered mice exposed to teratogens in utero. The goal is to understand how teratologic agents and genetic anomalies produce similar effects on the hindbrain. Project II. Behaviors Discriminating Autism in Humans and Animals, is an investigation of behavioral tasks with promise to discriminate autism from other developmental disabilities. The goal is to develop animal tasks that can serve as markers of the developmental abnormalities that cause autism so that animal models like those developed in Project I can be tested for parallelism to the human disorder. Inhibition of return and eyeblink conditioning are the tasks under study in this application. Project III, Genotype and Phenotype in Autism and Behaviorally-Related Disorders, has assessed behavioral symptomatology, minor physical anomalies, neurological / ophthalmological deficits, and mutations of early developmental genes in four groups with developmental disabilities (autism, Asperger syndrome, M bius syndrome, and language disorder) and controls with typical development. The investigators propose to add two groups - children with autism and mental retardation and IQ-matched controls. The goal is to determine whether the phenotypic or genotypic features of these disorders indicate common etiologies. Project IV, Gene-Environment Interactions in three Populations Exposed to Teratogens Associated with Autism, will examine six suspected genetic susceptibility factors in people exposed in utero to three teratogens known to be associated with autism: thalidomide, valproic acid, and misoprostol. The investigators propose to determine whether the members of these populations who meet diagnostic criteria for ASDs are ones with genetic risk factors. This project is closely related to the gene-environment studies proposed in animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIV PROTEASE INHIBITOR & LIPOPROTEIN RECEPTOR IMPAIRMENT Principal Investigator & Institution: Strickland, Dudley K.; Head, Department of Vascular Biology; American National Red Cross Washington, Dc 20037 Timing: Fiscal Year 2002; Project Start 12-JUL-2000; Project End 30-JUN-2005 Summary: This collaborative project, "Protease Inhibitors, Atherogenic Lipoproteins and Premature Atherosclerosis" comprises three proposals. Taken together, the studies will investigate potential atherosclerotic effects of protease inhibitors and assess their relationship to subclinical cardiovascular disease. The effects of HIV infection and associated antiretroviral therapy on plasma lipoprotein subclasses and pro-oxidant stress will be assessed under diverse clinical conditions to determine if HIV and its therapy, in particular protease inhibitors, induce a proatherogenic milieu. Mechanisms whereby protease inhibitors may promote atherosclerosis in humans will be explored in a series of clinical studies: utilizing antiretroviral regimens with and without protease inhibitors, treating uninfected volunteers and using thalidomide to reduce the effects of

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TNFalpha in patients with advanced HIV infection. In vitro cell culture experiments and animal models will be used to test the hypothesis that HIV protease inhibitors interfere with normal function of certain low density lipoprotein receptor family members, and that dysregulation of receptor function has a deleterious effect and may accelerate atherosclerosis. The presence of subclinical cardiovascular disease, and its relationship to the atherogenic lipoprotein phenotype and pro- oxidant stress levels will be assessed using several markers of atherosclerosis including flow-mediated brachial reactivity, carotid intima-media thickness, coronary calcification and electron beam computed tomographic angiography. The impact of intervention with gemfibrozil will also be examined. The three projects are interwoven, both through an umbrella hypothesis and shared experimental materials. Subjects recruited for each clinical project will provide samples or measures to be used in other projects' assays or analyses. Results from in vitro studies and the animal model will affect design of clinical studies. Shared resources include an administrative/statistical support group, NMR spectroscopic lipid laboratory and pro-oxidant stress laboratory. The investigators will conduct ongoing discussions of study procedures and results, both to ensure smooth interaction of the research groups and to stimulate new analyses and initiatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF CO-RECEPTOR AND HIV VIRAL BURDEN ON GUT MUCOSA Principal Investigator & Institution: Anton, Peter A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (adapted from the application's abstract): This application requests funds to allow the principal investigator, Dr. Peter Anton, to pursue clinical research on the quantification of mucosal viral loads and the characterization of mononuclear cells present in focal infections of HIV-1 in the intestinal mucosa. This work is based on newly developed methods in Dr. Anton's group to reproducibly isolate mucosal lympoid tissue. There are three specific aims. In Aim 1, Dr. Anton will continue with the optimization of the technique for isolation and characterization of mucosal lymphoid tissue to test the hypothesis that HIV infection is associated with mucosal inflammation. This part of the application will focus on the isolation of mononucelar cells and on quantitative methods to measure tissue RNA/DNA for HIV-1. In Aim 2, a study will be carried out to examine the correlation between CCR5 co-receptor expression and enhanced susceptibility to infection with HIV-1. Additionally, the relationship between HIV infection and D- chemokine expression (as a marker of inflammation) will be sought to test this hypothesis. In Aim 3, a clinical study will be executed to test the hypothesis that inflammation is a clinically significant feature of HIV persistence. This will be done by looking for decreased mucosal viral burden and evidence of immune reconstitution after therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IN VIVO IMAGING OF MOLECULAR TARGETS Principal Investigator & Institution: Gillies, Robert J.; Professor; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: Description (provided by applicant) One of the challenges facing oncology in the 21st century is the individualization of patient care. Tumors, even of the same type,

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have a wide range of presentation and a wide range of responses to both standard and novel therapies. Genotyping prior to therapy is showing great promise in allowing a choice of therapies for individual patients. After treatment has begun, however, methods to non-invasively detect the early response (or non-response) of individual tumors to therapy would be important to the overall goal of improved care for the individual patient. Hence, responders could be continued on successful therapy, and non-responders could be discontinued on ineffective and toxic therapy and moved to alternative therapies. The overall hypothesis of this project thus states that non-invasive imaging modalities can monitor the response of individual patients to therapy. In the context of the current proposal, non-invasive imaging can help develop and optimize novel therapeutic agents through the use of surrogate endpoints that are highly sensitive to the molecular target. Imaging methods are currently available which allow end-point assessment of therapeutic efficacy and these will be useful in assessing treatment protocols in pre-clinical and clinical settings. Additional imaging and spectroscopic methods will allow more direct assessment of proximal molecular consequences of drug action, and these will be developed. The specific aims of this Project are therefore: 4.1 To monitor apoptosis in vivo using two non-invasive imaging modalities, Technetium-labeled Annexin V Imaging and diffusion Magnetic Resonance Imaging, which are both in clinical trials. Apoptosis is a common endpoint for all of the therapies used in this program. This will be performed in both animal models and in human patients. 4.2 In collaboration with project 3 using SU-5416 and thalidomide, to monitor therapeutic response to anti-angiogenic drugs using dynamic contrastenhanced MR Imaging (DCE-MRI). This will be performed in both animal models and in human patients. 4.3 In collaboration with project I using DPIEL and Wortmannin, to use non-invasive magnetic resonance spectroscopy (MRS) to characterize the metabolic molecular signatures of tumor models before and after therapy with inhibitors of signal transduction. This will be performed in both animal models and in human patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAINLINE HEALTH CCOP Principal Investigator & Institution: Gilman, Paul B.; Lankenau Hospital 100 Lancaster Ave W Wynnewood, Pa 190963411 Timing: Fiscal Year 2002; Project Start 05-AUG-1994; Project End 31-MAY-2007 Summary: (provided by applicant): In this reapplication of the CCOP grant, we propose to maintain the Main Line Health CCOP as a consortium of oncology research programs between The Lankenau Hospital, Bryn Mawr Hospital, and Paoli Memorial Hospital. These three acute care hospitals are part of the Main Line Health System, whose service area includes the western and northwestern portions of Philadelphia County, into suburban Montgomery, Delaware and Chester Counties of Pennsylvania. This service area represents a population of over 1.2 million individuals of whom 15% are aged 65 or older. Main Line Health has blended the three hospitals oncology programs into a joint coordinated program, of which the CCOP is a part. Additionally, the three IRBs have merged and with the CCOP, this consortium continues to bring the communities stateof-the-art cancer care. The CCOP has developed affiliations with NSABP, ECOG, M.D. Anderson and RTOG to bring clinical trials to the area. These affiliations will continue, with a look to increasing accruals to these and other research based studies. Main Line Health has twelve medical oncologists, three gynecologic oncologists, eight surgical oncologists and ten radiation oncologists who see over 2000 patients annually, or 31 percent of the newly diagnosed cancer patients in our catchment area. We plan to continue to expand our available programs, increase ties to primary care physicians, and

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further develop involvement with minority and underserved populations for cancer prevention, control and treatment protocols. The ongoing commitment to cutting edge cancer prevention, diagnosis and treatment available through the research bases will allow the Main Line Health CCOP to continue to offer our communities state-of-the-art care for cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUNT SINAI COMMUNITY CLINICAL ONCOLOGY PROGRAM Principal Investigator & Institution: Lilenbaum, Rogerio C.; Mount Sinai Medical Center (Miami Beach) 4300 Alton Rd Miami Beach, Fl 331402800 Timing: Fiscal Year 2002; Project Start 13-JUL-1987; Project End 31-MAY-2007 Summary: (provided by applicant): Over the next five years, the overall aim of the CCOP is to reduce cancer incidence, morbidity, and mortality by accelerating the transfer of newly developed cancer prevention, early detection, treatment, patient management, rehabilitation, and continuing care technology to widespread community application. The immediate goals of the MSCCOP are to continue to increase our accrual rate to treatment and cancer control trials approved by NCI; to increase our ascending minority accrual in treatment and cancer control research; to maintain standards of excellence in data management; to cultivate contacts with primary care physicians and other specialists who may contribute to cancer control initiatives; to continue to refine cancer control data management capabilities, including the use of a range of resources to identify potential candidates for cancer control research projects; and to continue to develop our affiliate network of 7 clinical research sites in 5 cities. The track record of the MSCCOP demonstrates the ability to manage complex clinical research and cancer control activities while producing the highest quality data. The CCOP staffing pattern, protocol management procedures, patient/participant management approaches, quality control mechanisms, pharmacy control mechanisms, IRB structure and liaison are all in place and functioning to support current and future therapeutic and cancer control activities. The Mount Sinai Community Clinical Oncology Program provides access to national cooperative clinical trials to South Florida. The 6 hospitals in the MSCCOP see nearly 7000 newly diagnosed cancer patients per year, including rapidly rising minority and elderly populations. The MSCCOP brings together the strength and resources of a strong group of investigators who collaborate in the conduct of studies from CALGB, NSABP, RTOG, and the H. Lee Moffitt Cancer Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROPATHIC PAIN FROM AN EXPERIMENTAL NEURITIS Principal Investigator & Institution: Bennett, Gary J.; Professor; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 03-JUL-1998; Project End 30-JUN-2005 Summary: An experimental inflammation of the rat's sciatic nerve (a neuritis) has been produced by applying Complete Freunds Adjuvant to the surface of the nerve at the mid-thigh level. The neuritis produces heat- and mechano-hyperalgesia and cold- and mechano-allodynia in the ipsilateral hind paw that last for up to 5-6 days. At the time of peak symptom severity, there is an endoneurial immune cell infiltrate and evidence for plasma extravasation at the site of treatment, but little or no structural damage to axons or glia. The absence of degeneration and regeneration in the nerve, and the brief duration of the syndrome, are uniquely different than all present models of neuropathic pain. The mechanisms producing neuropathic pain in the territory of the inflamed nerve

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are likely to be distinctly different than those producing pain after cutaneous injury because the latter involves changes in receptor terminal transduction and impulse generation properties that are not present at "mid-axon" level. Our results suggest two novel concepts: (1) a focal, strictly inflammatory process in a nerve may give rise to neuropathic pain sensations in a distant region, and (2) such pain may be due to a neuroimmune interaction that generates ectopic discharge in uninjured nociceptor axons. The objectives of this proposal are to discover the causative factors involved in the genesis of the pain. Histological and immunocytochemical techniques will be used to determine the spatial and temporal extent of the inflammation, to identify the immune cell types that infiltrate the nerve, to determine whether pro-inflammatory cytokines and NGF are present, and to confirm the presence of plasma extravasation. To test whether a neuroimmune factor is involved, inhibitors of immune function will be given to see if they prevent the neuropathic pain. Electrophysiological recordings from identified sensory axons will determine if abnormal discharge arises at the site of inflammation and if there is peripheral sensitization due to an antidromically-conducted ectopic discharge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NORTHERN NEW JERSEY COMMUNITY CLINICAL ONCOLOGY PROGRAM Principal Investigator & Institution: Rosenbluth, Richard J.; Hackensack University Medical Center Hackensack, Nj 07601 Timing: Fiscal Year 2002; Project Start 01-SEP-1983; Project End 31-MAY-2007 Summary: (provided by applicant): The Northern New Jersey CCOP (NNJCCOP) provides access to clinical trials for cancer treatment and cancer control to almost half of the 8.4 million population of New Jersey, as well as adjacent New York and Pennsylvania. Forty-three physicians have access to trials, including pediatric and adult hematology/oncologists, surgeons, urologists, radiation oncologists, gynecologic oncologists and urologists. 37 Additional physicians are actively involved in the work of the CCOP. Extensive outreach ensures broad physician referral for cancer control. They are supported by a well-trained cadre of research nurses, pharmacists and data managers. The CCOP has created an effective and experienced infrastructure to ensure compliance with the highest standards of clinical research. The physicians build on a long tradition of closely-knit integration at the three clinical sites at two component hospitals. Hackensack University Medical Center (HUMC) includes a pediatric program, Tomorrows Children?s Institute (TCI) and an adult program, the Northern New Jersey Cancer Center (NNJCC). Trinitas Hospital, a component hospital resides in Union County, serving a high minority population. The two hospitals are primary sources of oncology care in their catchment areas and together accrue more than 2400 new cancer patients each year. The specific aims of the program are to: reduce cancer incidence, morbidity and mortality through expansion of clinical trials; develop creative and innovative means of communication, collaboration and education among physicians, health providers and citizens to accelerate cancer prevention, detection and treatment; ensure broader participation in trials among minority and female participants; and assure high standards of excellence and quality in cancer trials. Strong leadership, an effective organizational structure and proven track record support the goals of accelerated outreach, broad recruitment, expanded accrual, effective followup, accurate data management, compliance with quality assurance standards and active participation in the design, and implementation of new clinical trials. For the grant period, 2002-2007, the NNJCCOP projects accrual of 1482 adult credits (420 treatment

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and 1062 cancer control and follow-up) and 318.2 pediatric credits with 298 treatments and 20.2 cancer control credits. This represents a combined 5-year projected accrual of 1800.2 credits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUCLEOSIDE ANALOGS AS ANTICANCER COMPOUNDS Principal Investigator & Institution: Cheng, Yung-Chi; Professor; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 30-MAY-2006 Summary: The overall aim is to develop deoxynucleoside analogs for the treatment of patients with cancer. This includes the study of mechanism of action and resistance as well as the exploration of novel strategies to develop new nucleoside analogs with unique properties. In this application, we will continue to focus on the study of the anticancer action of a novel L-deoxynucleoside analog, L(-)dioxolane cytidine (L(-)OddC or BCH 4664) discovered in this laboratory and currently undergoing Phase II clinical studies. Based on the progress made, the Specific Aims are as follows: A. Study the role of AP endonuclease (APE/ref-I), which was identified to be the key activity in the removal of L(-)OddCMP from its 3'terminated DNA for the cytotoxic action of L()OddC. (1) Study the impact of unique mutations which could alter AP endonuclease activity or its redox regulatory activity, on its excision activity for the removal of L()OddCMP from its 3' -terminated DNA. (2) Study the impact of APE/ref-I, with or without unique mutations, on the action of L(-)OddC in cells. (3) Study the impact of thalidomide on the action of L(-)OddC with a focus on APE/ref-i expression. Examine the functional role of CMP/UMP kinase for the phosphorylation of L(-)OddCMP or dCMP to their diphosphate nucleotide forms. (1) Examine the impact of altering CMP/UMP kinase protein expression in cells on dCyd or L(-)OddC metabolism. (2) Examine the possible alteration of the state of CMP/UMP kinase protein through posttranslational modification or protein interaction in facilitating L(-)OddCMP or dCMP phosphorylation. (3) Examine the possible presence of dCMP kinase, which has not been identified, and its interaction with dCMP, CMP, UMP, L(-)OddCMP, AraCMP and dFdCydMP. The proposed study is based on some of the novel observations made during this funding period. It should provide information not only in terms of the action of all deoxycytidine analogs and their potential interaction with other classes of anticancer compounds, but also some basic knowledge regarding the biochemistry of nucleotide metabolism and DNA repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OPEN LABEL TRIAL OF THALIDOMIDE IN TREATMENT OF REFRACTORY CROHNS DISEASE Principal Investigator & Institution: Ehrenpreis, Eli D.; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 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: PHASE II TRIAL OF THALIDOMIDE IN PRIMARY AMYLOIDOSIS Principal Investigator & Institution: Dispenzieri, Angela; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905

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Timing: Fiscal Year 2002; Project Start 10-APR-2001; Project End 31-MAR-2004 Summary: (Provided by applicant): Primary systemic amyloidosis (AL amyloidosis) is a rare monoclonal plasma cell proliferative disorder. The disease is insidious, progressive, and uniformly fatal with a median survival of approximately 12-18 months. The AL amyloid protein fibrils deposit throughout the body and produce the characteristic clinical manifestations and syndromes. Response rates with standard alkylator therapy are only 20-30 percent. Peripheral stem cell transplantation may yield responses in 29-55 percent of patients, but concerns exist about selection bias confounding these data. The pathogenesis and treatment of primary systemic amyloidosis can be approached from several perspectives: the plasma cell clone and the bone marrow microenvironment; the clonal immunoglobulin fragment, which is the amyloid precursor; and the microenvironment of the target tissue, which supports amyloid deposition and possibly formation. This proposal is a therapeutic trial exploiting the favorable results seen with thalidomide in patients with multiple myeloma. The laboratory correlates are designed to study baseline characteristics and response characteristics at the level of the plasma cell clone and its microenvironment as well as of the amyloidogenic immunoglobulin and the amyloid fibril. For these studies, the clinical expertise of several Mayo Clinic investigators and of Dr Alan Solomon's group at the University of Tennessee will be utilized. This study will provide the opportunity to prospectively study information on bone marrow microvessels, vascular derived endothelial growth factor (VEGF) expression, apoptosis and proliferation of plasma cells, and amyloid fibril characteristics, both before and after therapy with thalidomide. Though primary systemic amyloidosis is a rare disorder, information about the plasma cell clone and immunoglobulin will be helpful not only to patients with AL amyloidosis but will also be useful in understanding two much less rare disorders, i.e. multiple myeloma and monoclonal gammopathy of undetermined significance. If thalidomide demonstrates activity in patients with primary systemic amyloidosis, we will use it as a component of a future multidrug Phase II trial, and the pertinent scientific correlates will be expanded upon based on positive findings. This "Quick Trials" (PA-00-047) application is designed to provide an essential research component to the clinical trial that will result in new knowledge on the pathogenesis of AL amyloidosis. The ultimate goal of the proposed studies is to improve the prognosis of patient with this fatal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT INVESTIGATION OF THE SAFETY AND EFFICACY OF THALIDOMIDE IN SCLERODERMA Principal Investigator & Institution: Oliver, Stephen J.; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002 Summary: Scleroderma is a connective tissue disease of unknown etiology characterized by excessive fibrosis of the skin and visceral organs. Scleroderma patients have not responded to traditional immunosuppressive and anti-inflammatory regimens, and the majority of these patients experience progressive disease with marked morbidity and mortality. Chronic graft versus host disease that occurs in bone marrow transplant patients shares many characteristics with scleroderma. In addition, recent reports have suggested that maternal-fetal exchange of cells across placental membranes and persistent microchimerism may contribute to scleroderma pathogenesis. The drug thalidomide, previously known for its teratogenic effects in the early 1960's, has since been found to have anti-inflammatory and immune-modulating effects in a number of immune mediated diseases, including graft-versus-host disease. Furthermore,

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preliminary studies suggest that the conventional treatment of graft-versus-host disease, cyclosporin A, may be effective in treating scleroderma. Thalidomide use has not been reported in scleroderma patients. This pilot study will obtain preliminary data on the safety and tolerability of thalidomide in scleroderma patients by establishing baseline clinical and serological profiles of patients and then follow those parameters during daily exposure to thalidomide over an initial dose escalation course over 12 weeks, with continued maintenance therapy for up to one year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT GANGRENOSUM

STUDY

OF

THALIDOMIDE

IN

PYODERMA

Principal Investigator & Institution: Haslett, Patrick A.; Research Associate; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: Pyoderma gangrenosum (PG) is a rare, ulcerative skin disorder of unknown etiology which has been reported to respond to treatment with thalidomide. The pathogenesis of PG is not known. The mechanism of action of thalidomide in this situation is also unknown. We have recently demonstrated that in vitro, thalidomide acts as a costimulator of T cells, increasing the secretion of Th-1 type cytokines. Our studies in patients with HIV infection and sarcoidosis have shown that soluble markers of T-cell activation, as well as plasma levels of interleukin-12, are consistently increased following thalidomide therapy. We hypothesize that thalidomide causes the healing of PG skin ulcers primarily by stimulating Th-1 T cells and promoting regulatory interactions between various cellular components of the immune system. Here we propose an open-label pilot study of thalidomide therapy for moderate-to-severe PG, in which we shall correlate clinical responses to therapy with peripheral blood markers of immune activation and function, as well as immunohistochemical analyses of perilesional cellular infiltrates. The identification of consistent immune correlates of clinical response will provide insights into the mechanism of action of thalidomide in this clinical setting, and more fundamentally, may shed light on the nature of the immune dysregulation which underlies the pathogenesis of PG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRAM PROJECT GROWTH CONTROL OF MULTIPLE MYELOMA Principal Investigator & Institution: Barlogie, Bart; Director; None; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 15-FEB-1993; Project End 31-MAY-2004 Summary: The objective of this Program Project is to develop therapeutic strategies that achieve sustained CR, based on insights gained from fundamental research and carefully controlled clinical trials. The research activities of this Program Project are based on the hypothesis that ultimate growth control of multiple myeloma can be achieved only through novel therapeutic interventions in the context of fundamental research of disease genetics and the biological mechanisms that sustain myeloma cell survival and progression. Six projects are proposed in this competing renewal application. The roles of anti-angiogenesis therapy with thalidomide and doseintensified consolidation therapy will be investigated via clinical trials in newly diagnosed patients (Proj 1), given our knowledge about critical obstacles to cure and the demonstrated efficacy of these treatment modalities. In patients treated previously for

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myeloma (Proj 2), standard melphalan-based stem cell transplantation will be compared to chemoangiotherapy. We expect that molecular identification of myeloma tumor suppressor gene(s), associated with the high risk chromosome 13 entity, will ultimately lead to better diagnosis and staging, as well as discovery of potentially novel growthregulatory molecules (Proj 3). As standard and high-dose therapies have both been shown to induce myelodysplasia (MDS) in a considerable fraction of patients, this adverse consequence of effective myeloma therapy will be studied prospectively in relationship to host and treatment variables (Proj 4). Biological and clinical observations of the roles of normal host accessory cells for the survival and expansion of myeloma cells can now be explored in the SCID-hu model, which lends itself to studying stromaldirected therapies that lead to tumor cell inactivation, such as pamidronate and thalidomide (Proj 5). Delineation of the mechanisms underlying the growth- inhibiting and bone-stimulating properties of syndecan-1 should lead to therapeutic exploitation either of this or related molecules (Proj 6). Three cores are proposed: Research Coordination and Administration; Biostatistics and Data Operations; and Cell Analysis. Thus, in the pursuit of achieving Growth Control in Multiple Myeloma, the collective work of basic and clinical scientists will shed light on the fundamental cellular and molecular mechanisms of myeloma growth and identify new means of tumor cell inactivation, thus aiding the design of rational, more effective, and safer therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPOPROTEIN

PROTEASE

INHIBITORS

INDUCE

AN

ATHEROGENIC

Principal Investigator & Institution: Simon, Gary L.; Medicine; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) This collaborative project, "Protease Inhibitors, Atherogenic Lipoproteins and premature Atherosclerosis" comprises three proposals. Taken together, the studies will investigate potential atherosclerotic effects of protease inhibitors and assess their relationship to subclinical cardiovascular disease. The effects of HIV infection and associated antiretroviral therapy on plasma lipoprotein subclasses and pro-oxidant stress will be assessed under diverse clinical conditions to determine if HIV and its therapy, in particular protease inhibitors, induce a proatherogenic milieu. Mechanisms whereby protease inhibitors may promote atherosclerosis in humans will be explored in a series of clinical studies: utilizing antiretroviral regimens with and without protease inhibitors, treating uninfected volunteers and using thalidomide to reduce the effects of TNF-alpha in patients with advanced HIV infection. In vitro cell culture experiments and animal models will be used to test the hypothesis that HIV protease inhibitors interfere with normal function of certain low density lipoprotein receptor family members, and that dysregulation of receptor function has a deleterious effect and may accelerate atherosclerosis. The presence of subclinical cardiovascular disease, and its relationship to the atherogenic lipoprotein phenotype and pro-oxidant stress levels will be assessed using several markers of atherosclerosis including flow-mediated brachial reactivity, carotid intimamedia thickness, coronary calcification and electron beam computed tomographic angiography. The impact of intervention with gemifibrozil will also be examined. The three projects are interwoven, both through an umbrella hypothesis and shared experimental materials. Subjects recruited for each clinical project will provide samples or measures to be used in other projects' assays or analyses. Results from in vitro studies

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and the animal model will affect design of clinical studies. Shared resources include an administrative/ statistical support group, NMR spectroscopic lipid laboratory and prooxidant stress laboratory. The investigators will conduct ongoing discussions of study procedures and results, both to ensure smooth interaction of the research groups and to stimulate new analyses and initiatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTITATIVE PERFUSION MRI

ASSESSMENT

OF

ANGIOGENESIS

BY

Principal Investigator & Institution: Johnson, Glyn; Associate Professor of Radiology; Radiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Broad long-term objectives: To develop methods of assessing angiogenesis in brain tumors using dynamic, contrast enhanced perfusion MRI (pMRI). Health-relatedness: The project will apply pMRI to the evaluation of brain tumors undergoing antioangiogenic and other chemotherapeutic treatments. However, the developed methods will also be useful in evaluating neoplastic lesions outside the brain and non-neoplastic lesions within it. Specific aims: 1) To investigate the hypothesis that pMRI measurements of cerebral blood volume (CBV) and vascular permeability correlate with histological assessments of vascularity and blood-brain barrier (BBB) breakdown respectively. 2) To determine whether pMRI can be used to grade brain tumors. 3) To investigate the hypothesis that pMRI can be used to monitor the efficacy of chemotherapeutic treatments. Research design: 1) Murine gliomas will be imaged with pMRI on a 7T animal imager. MRI measurements of CBV and vascular permeability will be correlated with histological assessments of vascular density and Evan's blue extravasation respectively. 2) CBV and vascular permeability will be measured in patients with histologically confirmed brain tumors of different grades to determine whether these measurements differentiate between them. 3) Serial pMRI measurements will be made on glioma patients enrolled in trials of new chemotherapeutic agents: thalidomide combined with carboplatin and the alkylating agents temodar and CPT-11. MRI measurements will be correlated with tumor size and clinical outcome to determine whether pMRI indications of angiogenesis predict tumor recurrence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF TNF ALPHA IN SLE Principal Investigator & Institution: Sullivan, Kathleen E.; Associate Professor of Pediatrics; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: (Adapted from the Investigator's abstract): Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disorder in which multiple susceptibility genes have been identified. The genes implicated in SLE fall into four categories: [1] antigen presentation, [2] immune complex clearance, [3] dysregulated antibody production, and [4] dysregulated T cell function. The investigator's preliminary data demonstrate an association of a TNF-alpha promoter polymorphism with SLE in African Americans. This promoter polymorphism (TNF-alpha-308A) is associated with increased TNF-alpha production that could potentially affect T and B cell apoptosis or development. The investigator has identified and purified a macrophage-specific complex that interacts

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with the TNF-alpha promoter at the polymorphic site. This complex consists of 64 kDa and 55 kDa proteins. The investigator has partially cloned one subunit, which is ubiquitously expressed and is related to the transcription factor Ets-1. The macrophagespecific complex interacts with the polymorphic promoter sequence with higher affinity than the wild-type sequence. The investigator hypothesizes that the complex's higher affinity for the polymorphic promoter sequence directly mediates increased transcription of TNF-alpha and that this increased TNF-alpha participates in the pathogenesis of SLE. There is now substantial evidence to support the idea that increased TNF-alpha is involved in the pathogenesis of SLE: [1] TNF-alpha-308A polymorphism is associated with SLE, [2] SLE patients have increased circulating TNFalpha and levels correlate with disease activity, [3] bone marrow cells from SLE patients spontaneously produce high levels of TNF-alpha, and [4] thalidomide treatment (which decreases TNF-alpha) results in clinical improvement. Animal models of SLE also support a role for TNF-alpha in the etiopathogenesis of SLE. MRL/lpr mice have high circulating TNF-alpha and interference with TNF-alpha expression ameliorates disease, and low doses of TNF-alpha accelerate disease in NZB/NZW mice. The investigator will independently confirm the association of TNF-alpha-308A with SLE in African Americans and Caucasians. She will examine the role of the macrophage-specific complex in the transcription of TNF-alpha by transient transfection techniques and they will directly measure differences in affinity of the protein for the wild type and polymorphic target sequences. She will also attempt to clone the gene encoding the second protein to identify its role in the binding interaction and the transcriptional regulation of TNF-alpha. This mechanistic approach will define the role of the macrophage-specific complex in the transcriptional regulation of TNF-alpha. These studies may ultimately enable rational interventions directed at TNF-alpha. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOUTHERN NEVADA CANCER RESEARCH FOUNDATION--CCOP Principal Investigator & Institution: Ellerton, John A.; Ccop Investigator; Southern Nevada Cancer Research Fdn Research Foundation Las Vegas, Nv 89106 Timing: Fiscal Year 2002; Project Start 30-SEP-1983; Project End 31-MAY-2007 Summary: (provided by applicant): The Southern Nevada Cancer Research Foundation (SNCRF) was established to conduct cancer research under the Community Clinical Oncology Program (CCOP) structure. It is a free standing non-hospital based CCOP. The long-term objectives have been: 1) to accrue a minimum of 50 credits annually to CCOP approved cooperative group treatment clinical trials; 2) to accrue a minimum of 50 credits annually to CCOP approved cooperative group cancer control studies; 3)to provide to the cooperative groups in the NCI timely data of high quality; 4)to promote quality and state-of-the-art treatment in the community through the participation in protocol studies by: (a) involving all CCOP physicians and staff in scientific and educational activities of the research bases; (b) expanding the knowledge, awareness and involvement of the primary health care providers and other specialists for the development and use of cancer control research; 5) to actively support other professional education programs and cancer control outreach services to under-served rural areas, and to identify women and minority groups that may be under-served and make a special effort to involve them in clinical trials; and 6) to actively work with the NCI to develop a community cancer network in order to facilitate the growth and development of important new cancer initiatives. In order to better accomplish all of these goals, the CCOP has expanded to include 45 investigators from varied medical specialties. The addition of Washoe Medical Center in 1999 as an affiliate in Reno

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expanded the CCOP statewide as the only CCOP in Nevada covering the entire state of Nevada. The CCOP continues to add new physicians every year to meet the growing population of the state. This will provide increased access to patients and increase public and medical awareness of the CCOP. The methods for accomplishing these goals will be through the application of CCOP grant money. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ST. VINCENT HOSPITAL REGIONAL CANCER CENTER CCOP Principal Investigator & Institution: Saphner, Thomas J.; St. Vincent Hospital 835 S Van Buren Green Bay, Wi 54301 Timing: Fiscal Year 2002; Project Start 09-AUG-2002; Project End 31-MAY-2005 Summary: (provided by applicant): St. Vincent Hospital Regional Cancer Center (SVRCC) is applying for CCOP funding in order to improve clinical care for the people of Northeast Wisconsin and the Upper Peninsula of Michigan. SVRCC is composed of St. Vincent Hospital, Green Bay Oncology (GBO), Radiation Oncology Associates (ROA), and Prevea Clinic Department of Pediatric Hematology and Oncology (PPHO). SVRCC is located in Green Bay, Wisconsin, and provides oncology services for the people of 13 counties of Northeast Wisconsin and the Upper Peninsula of Michigan. The broad, long-term goals of the proposed SVRCC CCOP are to provide the widest selection of cancer therapies for patients of the region and contribute to the general base of scientific and medical knowledge for the benefit of society at large. Specific aims of the proposed CCOP are to increase physician participation in clinical trials along with augmenting the number of new ideas and speeding their flow to the medical community of Green Bay and the surrounding region. An additional aim is to further professional interest in cancer treatment trials and increase participation in cancer prevention trials. These goals will be achieved by identifying National-Cancer-Instituteapproved clinical trials, helping to make them more readily available to physicians, and facilitating patient participation in them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ST.LOUIS-CAPE GIRARDEAU CCOP Principal Investigator & Institution: Henry, Patrick H.; Chairman; St.Louis-Cape Girardeau Ccop 12800 Corporate Hill Dr St. Louis, Mo 63131 Timing: Fiscal Year 2002; Project Start 01-JUN-1987; Project End 31-MAY-2007 Summary: (provided by applicant): The St. Louis-Cape Girardeau CCOP is a consortium of four hospitals in two separate bi-state health service areas serving parts of eastern Missouri and western Illinois. The Investigators from the St. Louis Metropolitan area are affiliated with one or both of the two hospitals in the consortium and have worked together for the past eighteen years in cancer treatment research protocols and more recently, in cancer control research studies. The Cape Girardeau Investigators have worked with CCOP for the past nine years and are affiliated with two hospitals in that city. During the next five years we expect to accrue at least sixty credits per year for cancer treatment research protocols of the NSABP and SWOG and at least seventy five credits (new participants and follow-up) per year for cancer control and prevention studies. These cancer control credits will be derived primarily from our participation in the Breast Cancer Prevention Trial-1, Prostate Cancer Prevention Trial-1 and the Breast Cancer Prevention Trial-2. We will continue to provide high quality data to the Southwest Oncology Group and the National Surgical Adjuvant Breast and Bowel Project which are our research bases, utilizing the data management system developed

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during the past eighteen years. In summary, we will continue our excellent performance of the past eighteen years in cancer treatment research studies and extend our more recent participation in cancer control and prevention trials. The past experience and capabilities of the Investigators and Clinical Research Associates provides a strong base for continuing development of this Community Clinical Oncology Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED MYELODYSPLASTIC S

INHIBITION

OF

ANGIOGENESIS

IN

Principal Investigator & Institution: List, Alan F.; Professor; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: Description (provided by applicant) The MDSs represent some of the most common hematologic malignancies, with an incidence that approximates that for chronic lymphocytic leukemia. Given the aging of the United States population and the absence of a standard effective treatment for these disorders, management of patients with MUDS has become increasingly problematic. The MDSs share the distinguishing features of ineffective hematopoiesis and increased risk of leukemia transformation. Recent studies have shown that these disorders display an increase in bone marrow (EM) microvessel density, the magnitude of which directly correlates with myeloblast percentage. We have shown that vascular endothelial growth factor (VEGF) and its receptors are expressed by myelomonocytic precursors in MDS and acute myelogenous leukemia (AML), and that VEGF elaboration contributes to suppression of committed progenitor growth and excess medullary generation of TNF alpha. Using the VEGFreceptor competent KG-1 AML cells as a model, we have characterized the biologic effects of VEGF in AML cells, which include suppression of nuclear translocation of NEB, stimulation of leukemia self renewal via interaction with either of the Fit-1 or KDR VEGF receptors, and activation of the phosphoinositol-3-kinase/Akt signaling pathway. We propose that agents which modify cellular VEGF elaboration or VEGF receptor signaling will impair leukemia progenitor self renewal, lower resistance to maturation signals, impair generation of inflammatory cytokines, and promote more effective hematopoiesis in MDS. Our efforts to delineate the VEGF receptor signaling pathway in AML progenitors provides a unique opportunity to validate in vivo target inhibition as an endpoint for biologic activity of novel therapeutics. In this project, we will investigate three Specific Aims that evaluate novel therapeutics which inhibit the actions of VEGF or its receptor signaling in patients with MDS, and delineate the relationship between in vivo target inhibition, and biologic and hematologic endpoints. The Specific Aims of this proposal are: 1) To determine the biologic effects of the VEGF inhibitor, thalidomide, in patients with MDS, and the relationship between target inhibition and hematologic response. 2) To investigate the molecular and pharmacologic effects of the VEGF receptor tyrosine kinase inhibitor, SU-5416, in vitro and in animal models. 3)To determine the biological effects of SU-5416 in patients with MDS, and the relation between hematologic response and VEGF -receptor tyrosine kinase inhibition in clinical specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETING INTERACTIONS

MYELOMA

CELL-HOST

BONE

MARROW

Principal Investigator & Institution: Anderson, Kenneth C.; Professor of Medicine; DanaFarber Cancer Institute 44 Binney St Boston, Ma 02115

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Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 30-JUN-2008 Summary: Multiple myeloma (MM) affected 14,400 new patients in the United States in 2001, with 50,000 total patients, and remains incurable despite conventional and high dose therapies. In order to overcome resistance to current therapies and improve patient outcome, novel biologically-based treatment approaches are needed which target mechanisms whereby MM cells grow and survive in the bone marrow (BM). Our preliminary in vitro and animal studies suggest a role for MM-host interactions in regulating MM cell growth, drug resistance, and migration in the BM. Moreover, our studies demonstrate that thalidomide and its potent immunomodulatory derivatives (IMiDs), proteasome inhibitor PS341, and arsenic trioxide As203 all target the MM cell in its BM milieu to overcome classical drug resistance both in vitro and in early clinical trials. In this context, we propose to carry out in vitro studies to characterize the role of the host BM microenvironment in promoting growth, survival, drug resistance, and migration of MM cells (Specific Aim 1) and then validate the growth, survival, drug resistance, and migratory signaling cascades triggered by MM cells in the host BM microenvironment as therapeutic targets (Specific Aim 2). These studies will provide the framework for validation of novel therapeutics targeting the MM-host BM interaction in vivo in animal models and in derived clinical trials (Specific Aim 3). These translational studies are directed to derive novel therapies to overcome drug resistance and improve outcome for patients with MM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TELOMERES AND TELOMERASE IN MYELOMA AND MDS Principal Investigator & Institution: Moore, M.A.S.; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002 Summary: (Applicant's Description) Myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML) occur with disconcerting frequency in myeloma patients following high-dose chemotherapy and autologous stem cell transplantation. In prospective and retrospective studies, we will evaluate several risk factors for these disorders. These include the nature of alkylating therapy, age, genetic predisposition, immunosuppression, antiangiogenesis therapy, and proliferative senescence within the hematopoietic system. Cytogenetic instability, involving short telomeres and chromosome end-fusion, associated with proliferative senescence is seen in telomerase knockout mice. Leukocyte telomere length will be measured serially to correlate progressive telomere shortening, stem cell destruction and development of aneuploidy and MDS. Qualitative and quantitative measures of the CD34+ population in patient marrow and mobilized peripheral blood will involve in vitro clonogenic assays, longterm stromal cell co-culture, and cytokine-driven serial expansion cultures. Stem-cell function will be further assessed using transendothelial chemotaxis assays, TRAP assay for telomerase levels, and NOD/SCID transplantation. These parameters, including evidence of proliferation and/or maturation defects associated with MDS, will be correlated with cytogenetic evaluation by G-banding and interphase fluorescence in situ hybridization (FISH). The study groups include patients on Total Therapy II and previously treated patients to determine whether autograft-supported, high-dose melphalan has a higher leukemogenic potential than DT-PACE. Increased telomerase levels are associated either with myeloma or MDS/AML, in order to overcome telomere shortening and proliferative senescence. We shall evaluate telomerase levels throughout therapy, to determine the prognostic and diagnostic value of this parameter, in conjunction with other features such as telomere length, cytogenetic status, and

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proliferative rate. Our observation of a therapyrelated "MDS/leukemic signature" among myeloma cells exhibiting a "myeloma signature" suggests a common evolutionary pathway progressing toward malignancy in both the plasma cell and myeloid lineage. The role of therapy, telomere shortening and telomerase activity will be assessed with respect to this phenomenon. We will also develop a retroviral genetransduction strategy for high expression of the human telomerase catalytic component in senescing CD34+ cells with short telomeres to explore this approach for telomere elongation and stem-cell rejuvenation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THALIDOMIDE FOR TREATMENT OF RECURRENT APHTHOUS ULCERS IN HIV Principal Investigator & Institution: Wohl, David A.; 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: THALIDOMIDE ON BODY COMPOSITION IN HIV WASTING Principal Investigator & Institution: Mannix, Edward T.; 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: THERAPEUTICS STUDIES OF PRIMARY CNS MALIGNANCIES Principal Investigator & Institution: Wen, Patrick Y.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 08-APR-1994; Project End 31-DEC-2002 Summary: The overall objective of this UOI application is to provide support for consortia of institutions to perform Phase I and 11 clinical trials of new chemotherapeutic/biologic agents in patients with primary central nervous system (CNS) tumors and to perform ancillary laboratory studies with potential clinical implications. The Harvard/Longwood Brain Tumor Center Trials Group at the DanaFarber Cancer Institute, Brigham and Women's Hospital, The Children's Hospital, and the Beth Israel Hospital has a large and expanding patient population and commitment to clinical and laboratory research of primary brain tumors. As part of the "North American Brain Tumor Consortium" our general goals will be to perform Phase I and II trials of novel cytotoxic and biologic agents, with a special interest in anti-angiogenic agents. Although San Antonio will function as the pharmacologic center for our consortium, our center is in a position to either pilot experimental and/or extensive single institution pharmacologic/pharmacodynamic studies given our large experience in pharmacology-based Phase I trials. Since the specific agents to be studied over the next four years are unknown at this time, we have chosen to develop protocols that build on our previous work in the pre-clinical and clinical development of three agents with anti-angiogenic activity based on our long-standing interest in tumor-associated angiogenesis: a.) Thalidomide, a teratogenic sedative with anti-angiogenic activity, for which we are just completed a promising Phase 11 trial in patients with malignant

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gliomas: b.) A new human beta interferon with anti-angiogenic activity and significant antiglioma activity demonstrated in our recently completed Phase I trial; and, c.) Angiostatin, a recently discovered endogenous inhibitor of angiogenesis, based on work done principally in our laboratories. The specific aims of this proposal are therefore; I.) To perform a Phase II trial of combination anti-angiogenesis inhibition with thalidornide and beta interferon in patients with recurrent high grade gliomas; and 2.) To perform a Phase I trial of angiostatin, a novel inhibitor of anti-angiogenesis, in patients with recurrent high grade gliomas. Through these examples, we hope to demonstrate our experience in the preclinical development and clinical trial design of novel agents to be evaluated in primary malignant gliomas, and our capability to develop correlative laboratory studies that may ultimately yield useful biologic and clinical endpoints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITION

TUMOR

PHYSIOLOGICAL

EFFECTS

OF

ANGIOGENESIS

Principal Investigator & Institution: Lee, William M.; Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 11-AUG-1999; Project End 30-JUN-2004 Summary: Angiogenesis inhibitors are being tested as cancer therapeutics with the idea of controlling tumor growth by preventing expansion of their blood supply, but little is known about the intermediary mechanisms and processes involved. Study of the effects of one inhibitor, rIL-12, within treated tumors reveals that a mechanism by which it controls tumor growth involves induction of severe tumor cell hypoxia and hypoxiainduced apoptosis. To establish whether angiogenesis inhibition leading to tumor hypoxia and hypoxia-induced apoptosis is a general physiological pathway invoked by these agents, Aim 1 is to examine the effect of selected antiangiogenic agents on tumor physiology. Effects of endostatin, thalidomide, thalidomide analogs and other putative angiogenesis inhibitors on tumor cell hypoxia, proliferation and apoptosis and on tumor vessel localization, density and patency will be examined. These studies will elucidate tumor mechanisms activated by antiangiogenesis therapy to control tumor growth. While induction of tumor hypoxia may be important for the therapeutic efficacy of angiogenesis inhibitors, it is also an environmental stress that can exert selective pressures on tumor cells. In Aim 2, the effect of iatrogenic hypoxia on cell selection in tumors will be examined by seeing if it results in the outgrowth of tumor cells engineered to better survive hypoxia. Other studies will examine tumors treated with antiangiogenic agents to see if cells emerge that resist hypoxia- induced apoptosis. These studies will indicate whether inhibitor therapy of tumors carries the potential risk of selecting tumor cells with diminished apoptotic potential. Angiogenesis inhibitors undoubtedly will be considered for use with radiation therapy. While tumor response to radiation may be improved by angiogenesis inhibition since both reduce and restrict tumor growth, the hypoxia that results from inhibitor use may engender radiation resistance. In Aim 3, the interaction between angiogenesis inhibitor and radiation therapy will be examined by studying the effect of radiation therapy alone and radiation given with antiangiogenic agents before and after they have induced tumor hypoxia. Measurement of tumor cell clonagenic survival, tumor remission, and the tumor physiological effects of therapy will detail the interaction between radiation and angiogenesis inhibitors in the presence and absence of hypoxia. Favorable and/or antagonistic interactions revealed by these studies can guide their combined clinical use and should elucidate the role of angiogenesis and tumor cell killing in tumor response to radiation therapy.

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

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

A Single Oral Dose of Thalidomide Enhances the Capacity of Lymphocytes to Secrete Gamma Interferon in Healthy Humans. by Verbon A, Juffermans NP, Speelman P, van Deventer SJ, ten Berge IJ, Guchelaar HJ, van der Poll T.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90059

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Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice. by Ruddy JM, Majumdar SK.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139116

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Binding of Thalidomide to [alpha]1-Acid Glycoprotein May be Involved in Its Inhibition of Tumor Necrosis Factor [alpha] Production. by Turk BE, Jiang H, Liu JO.; 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38783

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Disseminated Herpes Simplex Virus and Varicella Zoster Virus Coinfection in a Patient Taking Thalidomide for Relapsed Multiple Myeloma. by Curley MJ, Hussein SA, Hassoun PM.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130681

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Effective Immunomodulatory Treatment of Escherichia coli Experimental Sepsis with Thalidomide. by Giamarellos-Bourboulis EJ, Poulaki H, Kostomitsopoulos N, Dontas I, Perrea D, Karayannacos PE, Giamarellou H.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166096

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Generating Hypotheses by Discovering Implicit Associations in the Literature: A Case Report of a Search for New Potential Therapeutic Uses for Thalidomide. by Weeber M, Vos R, Klein H, de Jong-van den Berg LT, Aronson AR, Molema G.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=342048

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Lack of In Vitro Antimicrosporidian Activity of Thalidomide. by Ridoux O, Drancourt M.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89467

3 4

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

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

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Single-dose pharmacokinetics of thalidomide in human immunodeficiency virusinfected patients. by Piscitelli SC, Figg WD, Hahn B, Kelly G, Thomas S, Walker RE.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164214

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Thalidomide Inhibits Granulocyte Responses in Healthy Humans after Ex Vivo Stimulation with Bacterial Antigens. by Juffermans NP, Verbon A, Schultz MJ, Hack CE, van Deventer SJ, Speelman P, van der Poll T.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90503

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Thalidomide inhibits lipoarabinomannan-induced upregulation of human immunodeficiency virus expression. by Peterson PK, Gekker G, Bornemann M, Chatterjee D, Chao CC.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163036

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Thalidomide Inhibits the Replication of Human Immunodeficiency Virus Type 1. by Makonkawkeyoon S, Limson-Pobre RN, Moreira AL, Schauf V, Kaplan G.; 1993 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46849

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Thalidomide is an inhibitor of angiogenesis. by D'Amato RJ, Loughnan MS, Flynn E, Folkman J.; 1994 Apr 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43727

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Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. by Gordon GB, Spielberg SP, Blake DA, Balasubramanian V.; 1981 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319385

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Use of IMiD3, a Thalidomide Analog, as an Adjunct to Therapy for Experimental Tuberculous Meningitis. by Tsenova L, Mangaliso B, Muller G, Chen Y, Freedman VH, Stirling D, Kaplan G.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127267

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

A case of refractory Henoch-Schonlein purpura treated with thalidomide. Author(s): Choi SJ, Park SK, Uhm WS, Hong DS, Park HS, Park YL, Kwon KW. Source: Korean J Intern Med. 2002 December; 17(4): 270-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647645

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A novel subclass of thalidomide analogue with anti-solid tumor activity in which caspase-dependent apoptosis is associated with altered expression of bcl-2 family proteins. Author(s): Marriott JB, Clarke IA, Czajka A, Dredge K, Childs K, Man HW, Schafer P, Govinda S, Muller GW, Stirling DI, Dalgleish AG. Source: Cancer Research. 2003 February 1; 63(3): 593-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566301

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A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Author(s): Mesa RA, Steensma DP, Pardanani A, Li CY, Elliott M, Kaufmann SH, Wiseman G, Gray LA, Schroeder G, Reeder T, Zeldis JB, Tefferi A. Source: Blood. 2003 April 1; 101(7): 2534-41. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517815

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A pilot study of thalidomide for patients with symptomatic mesenteric panniculitis. Author(s): Ginsburg PM, Ehrenpreis ED. Source: Alimentary Pharmacology & Therapeutics. 2002 December; 16(12): 2115-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452945

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A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis. Author(s): Austin AS, Mahida YR, Clarke D, Ryder SD, Freeman JG. Source: Alimentary Pharmacology & Therapeutics. 2004 January 1; 19(1): 79-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687169

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A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndrome. Author(s): Cortes J, Kantarjian H, Albitar M, Thomas D, Faderl S, Koller C, GarciaManero G, Giles F, Andreeff M, O'Brien S, Keating M, Estey E. Source: Cancer. 2003 March 1; 97(5): 1234-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12599230

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A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple myeloma. Author(s): Rajkumar SV, Witzig TE. Source: Cancer Treatment Reviews. 2000 October; 26(5): 351-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11006136

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A single oral dose of thalidomide enhances the capacity of lymphocytes to secrete gamma interferon in healthy humans. Author(s): Verbon A, Juffermans NP, Speelman P, van Deventer SJ, ten Berge IJ, Guchelaar HJ, van der Poll T. Source: Antimicrobial Agents and Chemotherapy. 2000 September; 44(9): 2286-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10952569

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A tale of two experts: thalidomide and political engagement in the United States and West Germany. Author(s): Daemmrich A. Source: Social History of Medicine : the Journal of the Society for the Social History of Medicine / Sshm. 2002 April; 15(1): 137-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12625358

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Activity of thalidomide in AIDS-related Kaposi's sarcoma. Author(s): Little RF, Wyvill KM, Pluda JM, Welles L, Marshall V, Figg WD, Newcomb FM, Tosato G, Feigal E, Steinberg SM, Whitby D, Goedert JJ, Yarchoan R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 July; 18(13): 2593-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10893291

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Adjunctive thalidomide therapy of childhood tuberculous meningitis: possible antiinflammatory role. Author(s): Schoeman JF, Springer P, Ravenscroft A, Donald PR, Bekker LG, van Rensburg AJ, Hanekom WA, Haslett PA, Kaplan G. Source: Journal of Child Neurology. 2000 August; 15(8): 497-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961786

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Advances in the treatment of multiple myeloma: the role of thalidomide. Author(s): Ribas C, Colleoni GW. Source: Leukemia & Lymphoma. 2003 February; 44(2): 291-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688347

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Alleviation of systemic manifestations of multicentric Castleman's disease by thalidomide. Author(s): Lee FC, Merchant SH. Source: American Journal of Hematology. 2003 May; 73(1): 48-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12701121

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Alpha-fluoro-substituted thalidomide analogues. Author(s): Man HW, Corral LG, Stirling DI, Muller GW. Source: Bioorganic & Medicinal Chemistry Letters. 2003 October 20; 13(20): 3415-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505639

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An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer. Author(s): Drake MJ, Robson W, Mehta P, Schofield I, Neal DE, Leung HY. Source: British Journal of Cancer. 2003 March 24; 88(6): 822-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644816

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An UK myeloma forum phase II study of thalidomide; long term follow-up and recommendations for treatment. Author(s): Schey SA, Cavenagh J, Johnson R, Child JA, Oakervee H, Jones RW. Source: Leukemia Research. 2003 October; 27(10): 909-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860011

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Angiosarcoma of the small intestine: a possible role for thalidomide? Author(s): Fraiman G, Ganti AK, Potti A, Mehdi S. Source: Medical Oncology (Northwood, London, England). 2003; 20(4): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716038

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Antiangiogenic activity of N-substituted and tetrafluorinated thalidomide analogues. Author(s): Ng SS, Gutschow M, Weiss M, Hauschildt S, Teubert U, Hecker TK, Luzzio FA, Kruger EA, Eger K, Figg WD. Source: Cancer Research. 2003 June 15; 63(12): 3189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810647

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Antiphospholipid syndrome triggered by thalidomide in a patient with discoid lupus erythematosus. Author(s): Tektonidou MG, Vlachoyiannopoulos PG. Source: Lupus. 2003; 12(9): 723-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514139

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Australia approves thalidomide. Author(s): Habeck M. Source: The Lancet Oncology. 2003 December; 4(12): 713. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14682348

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Behcet disease and the emergence of thalidomide. Author(s): Ehrlich GE. Source: Annals of Internal Medicine. 1998 March 15; 128(6): 494-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9499334

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Behcet's disease in UK children: clinical features and treatment including thalidomide. Author(s): Kari JA, Shah V, Dillon MJ. Source: Rheumatology (Oxford, England). 2001 August; 40(8): 933-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511764

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Behcet's disease, palmoplantar pustulosis and HLA-B27 treatment with thalidomide. Author(s): Hamza M. Source: Clin Exp Rheumatol. 1990 July-August; 8(4): 427. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2397633

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Benzylphthalimides and phenethylphthalimides with thalidomide-like activity on the production of tumor necrosis factor alpha. Author(s): Sasaki K, Shibata Y, Hashimoto Y, Iwasaki S. Source: Biological & Pharmaceutical Bulletin. 1995 September; 18(9): 1228-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8845811

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Binding of thalidomide to alpha1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production. Author(s): Turk BE, Jiang H, Liu JO. Source: Proceedings of the National Academy of Sciences of the United States of America. 1996 July 23; 93(15): 7552-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8755512

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Bradycardia during therapy for multiple myeloma with thalidomide. Author(s): Fahdi IE, Gaddam V, Saucedo JF, Kishan CV, Vyas K, Deneke MG, Razek H, Thorn B, Bissett JK, Anaisse E, Barlogie B, Mehta JL. Source: The American Journal of Cardiology. 2004 April 15; 93(8): 1052-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081457

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Can thalidomide be effective to treat plasma cell leptomeningeal infiltration? Author(s): Vicari P, Ribas C, Sampaio M, Arantes AM, Yamamoto M, Filho JB, Segreto RA, Bordin JO, Colleoni GW. Source: European Journal of Haematology. 2003 March; 70(3): 198-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605668

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Chemical stabilities and biological activities of thalidomide and its N-alkyl analogs. Author(s): Goosen C, Laing TJ, du Plessis J, Goosen TC, Rao TB, Flynn GL. Source: Pharmaceutical Research. 2002 August; 19(8): 1232-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12240951

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Chronic graft-versus-host disease revealed by lichenoid vulvar lesions successfully treated with thalidomide. Author(s): Staumont-Salle D, Magro L, Piette F, Thomas P, Jouet JP, Catteau B. Source: Acta Dermato-Venereologica. 2003; 83(4): 302-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926809

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Clinical and immunologic parameters during thalidomide treatment of lupus erythematosus. Author(s): Walchner M, Meurer M, Plewig G, Messer G. Source: International Journal of Dermatology. 2000 May; 39(5): 383-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10849134

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Clinical and immunological benefit of adjuvant therapy with thalidomide in the treatment of tuberculosis disease. Author(s): Gori A, Rossi MC, Marchetti G, Trabattoni D, Molteni C, Cogliati M, Bandera A, Clerici M, Franzetti F. Source: Aids (London, England). 2000 August 18; 14(12): 1859-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10985328

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Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis with myeloid metaplasia. A pilot study. Author(s): Piccaluga PP, Visani G, Pileri SA, Ascani S, Grafone T, Isidori A, Malagola M, Finelli C, Martinelli G, Ricci P, Baccarani M, Tura S. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 September; 16(9): 1609-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200671

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Clinical trials referral resource. Current clinical trials of thalidomide. Author(s): Streicher HZ, Vereshchagina LA, Schoenfeldt M. Source: Oncology (Huntingt). 2003 March; 17(3): 369-71, 374-5, 379-80. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661268

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Combination therapy of Thalidomide and Peginterferon in patients with progressive multiple myeloma. Author(s): Kasper B, Moehler T, Neben K, Ho AD, Goldschmidt H. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 January; 15(1): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679142

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Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice. Author(s): Fujii T, Tachibana M, Dhar DK, Ueda S, Kinugasa S, Yoshimura H, Kohno H, Nagasue N. Source: Anticancer Res. 2003 May-June; 23(3B): 2405-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894521

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Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. Author(s): Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 November 1; 20(21): 4319-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409330

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Combined thalidomide and temozolomide treatment in patients with glioblastoma multiforme. Author(s): Baumann F, Bjeljac M, Kollias SS, Baumert BG, Brandner S, Rousson V, Yonekawa Y, Bernays RL. Source: Journal of Neuro-Oncology. 2004 March-April; 67(1-2): 191-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072467

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Comment on thalidomide usage in myeloma. Author(s): Myers B. Source: Haematologica. 2002 June; 87(6): Elt29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031937

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Consolidation therapy of multiple myeloma with thalidomide-dexamethasone after intensive chemotherapy. Author(s): Alexanian R, Weber D, Giralt S, Delasalle K. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 July; 13(7): 1116-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176792

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Continuing education: The emergence of thalidomide in treating advanced renal cell carcinoma. Author(s): Wood LS, Perez C, Monroe D. Source: Oncology Nursing Forum. 2003 May-June; 30(3): 501-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719749

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Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts. Author(s): Kinuya S, Kawashima A, Yokoyama K, Koshida K, Konishi S, Watanabe N, Shuke N, Bunko H, Michigishi T, Tonami N. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 August; 43(8): 1084-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12163635

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Correspondence re: K. Neben et al., high plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Clin. Cancer Res., 7: 2675-2681, 2001. Author(s): Go RS, Horstman AL. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 August; 8(8): 2750; Author Reply 2751. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12171909

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Current role of thalidomide in cancer treatment. Author(s): Thomas DA, Kantarjian HM. Source: Current Opinion in Oncology. 2000 November; 12(6): 564-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11085456

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Cutaneous Rosai-Dorfman disease: remission with thalidomide treatment. Author(s): Tjiu JW, Hsiao CH, Tsai TF. Source: The British Journal of Dermatology. 2003 May; 148(5): 1060-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786846

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Cytogenetic response to thalidomide treatment in three patients with myelodysplastic syndrome. Author(s): Strupp C, Hildebrandt B, Germing U, Haas R, Gattermann N. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 June; 17(6): 1200-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12764395

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Cytokine modulation and suppression of liver injury by a novel analogue of thalidomide. Author(s): Thiele A, Bang R, Gutschow M, Rossol M, Loos S, Eger K, Tiegs G, Hauschildt S. Source: European Journal of Pharmacology. 2002 October 25; 453(2-3): 325-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398921

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Deep venous thrombosis and thalidomide therapy for multiple myeloma. Author(s): Osman K, Comenzo R, Rajkumar SV. Source: The New England Journal of Medicine. 2001 June 21; 344(25): 1951-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11419443

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Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. Author(s): Cavo M, Zamagni E, Cellini C, Tosi P, Cangini D, Cini M, Valdre L, Palareti G, Masini L, Tura S, Baccarani M. Source: Blood. 2002 September 15; 100(6): 2272-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12229885

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Dermatologic and nondermatologic uses of thalidomide. Author(s): Nasca MR, Micali G, Cheigh NH, West LE, West DP. Source: The Annals of Pharmacotherapy. 2003 September; 37(9): 1307-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921515

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Dermatologic side effects of thalidomide in patients with multiple myeloma. Author(s): Hall VC, El-Azhary RA, Bouwhuis S, Rajkumar SV. Source: Journal of the American Academy of Dermatology. 2003 April; 48(4): 548-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12664018

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Despite checkered past, thalidomide and its analogues show potential. Author(s): Friedrich MJ. Source: Journal of the National Cancer Institute. 2002 September 4; 94(17): 1270-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208890

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Determination of thalidomide in transport buffer for Caco-2 cell monolayers by highperformance liquid chromatography with ultraviolet detection. Author(s): Zhou S, Li Y, Kestell P, Paxton JW. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 February 25; 785(1): 165-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535849

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Development of a myeloproliferative disorder in a patient with monoclonal gammopathy of undetermined significance secreting immunoglobulin of the M class and treated with thalidomide and anti-CD20 monoclonal antibody. Author(s): Kyrtsonis MC, Kokoris SI, Kontopidou FN, Siakantaris MP, Kittas C, Pangalis GA. Source: Blood. 2001 April 15; 97(8): 2527-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307775

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Diabetic foot disease in a patient with multiple myeloma receiving thalidomide. Author(s): Pitini V, Arrigo C, Aloi G, Azzarello D, La Gattuta G. Source: Haematologica. 2002 February; 87(2): Elt07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836184

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Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. Author(s): Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, Patterson RT, Stirling DI, Kaplan G. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 July 1; 163(1): 380-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10384139

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Differential effect of thalidomide and dexamethasone on the transcription factor NFkappa B. Author(s): Rowland TL, McHugh SM, Deighton J, Ewan PW, Dearman RJ, Kimber I. Source: International Immunopharmacology. 2001 January; 1(1): 49-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11367517

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Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Author(s): Rowland TL, McHugh SM, Deighton J, Dearman RJ, Ewan PW, Kimber I. Source: Immunopharmacology. 1998 July; 40(1): 11-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9776474

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Differential regulation of dendritic cell function by the immunomodulatory drug thalidomide. Author(s): Mohty M, Stoppa AM, Blaise D, Isnardon D, Gastaut JA, Olive D, Gaugler B. Source: Journal of Leukocyte Biology. 2002 November; 72(5): 939-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429715

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Disfiguring cutaneous manifestation of sarcoidosis treated with thalidomide: a case report. Author(s): Lee JB, Koblenzer PS. Source: Journal of the American Academy of Dermatology. 1998 November; 39(5 Pt 2): 835-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9810910

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Disseminated herpes simplex virus and varicella zoster virus coinfection in a patient taking thalidomide for relapsed multiple myeloma. Author(s): Curley MJ, Hussein SA, Hassoun PM. Source: Journal of Clinical Microbiology. 2002 June; 40(6): 2302-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037117

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Does thalidomide cause second generation birth defects? Author(s): Smithells D. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1998 November; 19(5): 339-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825947

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Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma. Author(s): Neben K, Moehler T, Benner A, Kraemer A, Egerer G, Ho AD, Goldschmidt H. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 November; 8(11): 3377-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429624

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Down-regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro treatment with the anti-TNF-alpha agent thalidomide. Author(s): Settles B, Stevenson A, Wilson K, Mack C, Ezell T, Davis MF, Taylor LD. Source: Cell Mol Biol (Noisy-Le-Grand). 2001 November; 47(7): 1105-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838958

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DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. Author(s): Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J, van Rhee F, Cottler-Fox M, Muwalla F, Tricot G. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 15; 21(14): 2732-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860952

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Durable clinical response of refractory hepatocellular carcinoma to orally administered thalidomide. Author(s): Patt YZ, Hassan MM, Lozano RD, Ellis LM, Peterson JA, Waugh KA. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2000 June; 23(3): 319-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10857902

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Dynamic contrast-enhanced T2-weighted MR imaging of recurrent malignant gliomas treated with thalidomide and carboplatin. Author(s): Cha S, Knopp EA, Johnson G, Litt A, Glass J, Gruber ML, Lu S, Zagzag D. Source: Ajnr. American Journal of Neuroradiology. 2000 May; 21(5): 881-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10815664

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Early changes in bone marrow morphology induced by thalidomide in refractory myeloma patients. Author(s): Corso A, Lorenzi A, Zappasodi P, Invernizzi R, Vanelli L, Lazzarino M. Source: Haematologica. 2003 August; 88(8): 958-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935985

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Effect of a high-fat meal on thalidomide pharmacokinetics and the relative bioavailability of oral formulations in healthy men and women. Author(s): Teo SK, Scheffler MR, Kook KA, Tracewell WG, Colburn WA, Stirling DI, Thomas SD. Source: Biopharmaceutics & Drug Disposition. 2000 January; 21(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11038436

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Effect of thalidomide in patients with chronic heart failure. Author(s): Gullestad L, Semb AG, Holt E, Skardal R, Ueland T, Yndestad A, Froland SS, Aukrust P. Source: American Heart Journal. 2002 November; 144(5): 847-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422154

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Effect of thalidomide on chemokine production by human microglia. Author(s): Lokensgard JR, Hu S, van Fenema EM, Sheng WS, Peterson PK. Source: The Journal of Infectious Diseases. 2000 September; 182(3): 983-7. Epub 2000 August 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950803

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Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Author(s): Govindarajan R, Heaton KM, Broadwater R, Zeitlin A, Lang NP, HauerJensen M. Source: Lancet. 2000 August 12; 356(9229): 566-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950238

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Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. Author(s): Ghobrial IM, Dispenzieri A, Bundy KL, Gastineau DA, Rajkumar SV, Therneau TM, Lacy MQ, Witzig TE, Litzow MR, Christensen BR, Hayman S, Pribula CG, Gertz MA. Source: Bone Marrow Transplantation. 2003 September; 32(6): 587-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953131

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Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma. Author(s): Kumar S, Witzig TE, Dispenzieri A, Lacy MQ, Wellik LE, Fonseca R, Lust JA, Gertz MA, Kyle RA, Greipp PR, Rajkumar SV. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 March; 18(3): 624-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749707

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Effective immunomodulatory treatment of Escherichia coli experimental sepsis with thalidomide. Author(s): Giamarellos-Bourboulis EJ, Poulaki H, Kostomitsopoulos N, Dontas I, Perrea D, Karayannacos PE, Giamarellou H. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2445-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878503

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Effective treatment of oral erosive lichen planus with thalidomide. Author(s): Camisa C, Popovsky JL. Source: Archives of Dermatology. 2000 December; 136(12): 1442-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115153

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Effects of thalidomide on parameters involved in angiogenesis: an in vitro study. Author(s): Gelati M, Corsini E, Frigerio S, Pollo B, Broggi G, Croci D, Silvani A, Boiardi A, Salmaggi A. Source: Journal of Neuro-Oncology. 2003 September; 64(3): 193-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14558594

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Effects of thalidomide on the expression of angiogenesis growth factors in human A549 lung adenocarcinoma cells. Author(s): Li X, Liu X, Wang J, Wang Z, Jiang W, Reed E, Zhang Y, Liu Y, Li QQ. Source: International Journal of Molecular Medicine. 2003 June; 11(6): 785-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736723

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Efficacy of thalidomide in a child with histiocytic sarcoma following allogeneic bone marrow transplantation for T-ALL. Author(s): Dalle JH, Leblond P, Decouvelaere A, Yakoub-Agha I, Preudhomme C, Nelken B, Mazingue F. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 October; 17(10): 2056-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513060

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Efficacy of thalidomide in refractory adult Still's disease: a new case report. Author(s): Meaux-Ruault N, Magy N, Gil H, Dupond JL. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 272. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747295

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Efficacy of thalidomide in the treatment of VAD-refractory plasma cell leukaemia appearing after autologous stem cell transplantation for multiple myeloma. Author(s): Bauduer F. Source: British Journal of Haematology. 2002 June; 117(4): 996-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060146

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Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. Author(s): Schafer PH, Gandhi AK, Loveland MA, Chen RS, Man HW, Schnetkamp PP, Wolbring G, Govinda S, Corral LG, Payvandi F, Muller GW, Stirling DI. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 June; 305(3): 1222-32. Epub 2003 March 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649301

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Evaluation of thalidomide for treatment or prevention of chronic graft-versus-host disease. Author(s): Flowers ME, Martin PJ. Source: Leukemia & Lymphoma. 2003 July; 44(7): 1141-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916865

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Evaluation of thrombophylic states in myeloma patients receiving thalidomide: a reasonable doubt. Author(s): Santos AB, Llamas P, Roman A, Prieto E, De Ona R, De Velasco JF, Tomas JF. Source: British Journal of Haematology. 2003 July; 122(1): 159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823358

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Exacerbation of psoriasis by thalidomide in Behcet's syndrome. Author(s): Dobson CM, Parslew RA. Source: The British Journal of Dermatology. 2003 August; 149(2): 432-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932265

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Expression of angiogenic factors including VEGFs and the effects of hypoxia and thalidomide on human myeloma cells. Author(s): Yata K, Otsuki T, Kurebayashi J, Uno M, Fujii T, Yawata Y, Takata A, Hyodoh F, Sugihara T. Source: International Journal of Oncology. 2003 January; 22(1): 165-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469200

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Extremely high levels of von Willebrand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. Author(s): Minnema MC, Fijnheer R, De Groot PG, Lokhorst HM. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 March; 1(3): 445-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871448

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Failure of thalidomide to control bronchiolitis obliterans post bone marrow transplant. Author(s): Heaton DC. Source: Bone Marrow Transplantation. 1989 September; 4(5): 598. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2790340

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F-chronodispersion in patients on thalidomide. Author(s): Sadoh DR, Hawk JL, Panayiotopoulos CP. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 April; 110(4): 735-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10378746

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FDA approves fomivirsen, famciclovir, and Thalidomide. Food and Drug Administration. Author(s): Highleyman L. Source: Beta. 1998 October; : 5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11365993

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Finding new uses for thalidomide. Author(s): Gershon D. Source: Nature Medicine. 1995 December; 1(12): 1230. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7489393

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Five years' experience with thalidomide treatment in leprosy reaction. Author(s): Sheskin J, Sagher F. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 1971 April-June; 39(2): 585-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4948092

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Formed by thalidomide: mass torts as a false cure for toxic exposure. Author(s): Bernstein A. Source: Columbia Law Rev. 1997 November; 97(7): 2153-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10181029

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Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma. Author(s): Juliusson G, Celsing F, Turesson I, Lenhoff S, Adriansson M, Malm C. Source: British Journal of Haematology. 2000 April; 109(1): 89-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10848786

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Full compensation for 20 thalidomide victims. Author(s): Roper J. Source: Times (Lond). 1978 August 4; : 1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11648976

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Full-thickness skin grafting of eyelids in a patient with generalized morphea taking thalidomide. Author(s): Periman LM, Sires BS. Source: Archives of Ophthalmology. 2000 January; 118(1): 135-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636434

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Further observation with thalidomide in lepra reactions. Author(s): Sheskin J. Source: Lepr Rev. 1965 October; 36(4): 183-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5871249

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Further problems with thalidomide. Author(s): Tweedle D. Source: Journal of the Royal College of Surgeons of Edinburgh. 1990 February; 35(1): 63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2342019

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Further problems with thalidomide. Author(s): James NK, Leaper DJ. Source: Journal of the Royal College of Surgeons of Edinburgh. 1989 June; 34(3): 167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2810175

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Generating hypotheses by discovering implicit associations in the literature: a case report of a search for new potential therapeutic uses for thalidomide. Author(s): Weeber M, Vos R, Klein H, De Jong-Van Den Berg LT, Aronson AR, Molema G. Source: Journal of the American Medical Informatics Association : Jamia. 2003 MayJune; 10(3): 252-9. Epub 2003 January 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626374

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Gliomatosis cerebri: post-mortem molecular and immunohistochemical analyses in a case treated with thalidomide. Author(s): Mawrin C, Aumann V, Kirches E, Schneider-Stock R, Scherlach C, Vogel S, Mittler U, Dietzmann K, Krause G, Weis S. Source: Journal of Neuro-Oncology. 2001 October; 55(1): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804278

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Growing interest in thalidomide. Author(s): Lowell B. Source: Gmhc Treat Issues. 1995 May; 9(5): 4-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11362414

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Guideline for the clinical use and dispensing of thalidomide. Author(s): Powell RJ, Gardner-Medwin JM. Source: Postgraduate Medical Journal. 1994 December; 70(830): 901-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7870638

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Guidelines for the clinical use and dispensing of thalidomide. Author(s): Judge MR, Kobza-Black A, Hawk JL. Source: Postgraduate Medical Journal. 1995 February; 71(832): 123. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7724427

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Habilitation of thalidomide children: the nursing approach. Author(s): O'Brien MO, Owens M, Ralph J. Source: Can Nurse. 1967 January; 63(1): 26-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6015536

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Hand and foot preference in thalidomide children. Author(s): Smithells RW. Source: Archives of Disease in Childhood. 1970 April; 45(240): 274. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5420002

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Handling of blood samples for determination of thalidomide. Author(s): Eriksson T, Bjorkman S. Source: Clinical Chemistry. 1997 June; 43(6 Pt 1): 1094-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9191574

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Hazards to the newlyborn infant from thalidomide-containing drugs administered to pregnant mothers. (Report on three cases). Author(s): Sakr R, el-Zawahry K, Khalifa AS, Aboul Hassan A, Khalil M. Source: J Egypt Med Assoc. 1966; 49(1): 78-87. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5959538

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Head of German medicines body likens HRT to thalidomide. Author(s): Burgermeister J. Source: Bmj (Clinical Research Ed.). 2003 October 4; 327(7418): 767. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525858

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Health of thalidomide victims and their progeny. Author(s): McBride W. Source: Lancet. 2004 January 10; 363(9403): 169. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726182

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High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Author(s): Neben K, Moehler T, Egerer G, Kraemer A, Hillengass J, Benner A, Ho AD, Goldschmidt H. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 September; 7(9): 2675-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555579

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High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graftversus-host disease. Author(s): Boughton BJ, Sheehan TM, Wood J, O'Brien D, Butler M, Simpson A, Hale KA. Source: Annals of Clinical Biochemistry. 1995 January; 32 ( Pt 1): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7762955

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HIV-associated oesophageal ulcers treated with thalidomide. Author(s): Georghiou PR, Kemp RJ. Source: The Medical Journal of Australia. 1990 April 2; 152(7): 382-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2093810

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Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations. Author(s): Van Regemorter N, Haumont D, Kirkpatrick C, Viseur P, Jeanty P, Dodion J, Milaire J, Rooze M, Rodesch F. Source: European Journal of Pediatrics. 1982 February; 138(1): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7075631

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Human teratogenesis: invitro studies on thalidomide-inhibited chondrogenesis. Author(s): Lash JW, Saxen L. Source: Developmental Biology. 1972 May; 28(1): 61-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5041198

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Hydrolysis of thalidomide abrogates its ability to enhance mononuclear cell synthesis of IL-2 as well as its ability to suppress the synthesis of TNF-alpha. Author(s): Shannon EJ, Sandoval F, Krahenbuhl JL. Source: Immunopharmacology. 1997 April; 36(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9129992

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Hydroxylated metabolites of thalidomide: formation in-vitro and in-vivo in man. Author(s): Eriksson T, Bjorkman S, Roth B, Bjork H, Hoglund P. Source: The Journal of Pharmacy and Pharmacology. 1998 December; 50(12): 1409-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10052858

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Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Author(s): Kropff MH, Lang N, Bisping G, Domine N, Innig G, Hentrich M, Mitterer M, Sudhoff T, Fenk R, Straka C, Heinecke A, Koch OM, Ostermann H, Berdel WE, Kienast J. Source: British Journal of Haematology. 2003 August; 122(4): 607-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899716

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Hypothesis: thalidomide embryopathy-proposed mechanism of action. Author(s): Stephens TD, Fillmore BJ. Source: Teratology. 2000 March; 61(3): 189-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10661908

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Hypothyroidism in patients with multiple myeloma following treatment with thalidomide. Author(s): Badros AZ, Siegel E, Bodenner D, Zangari M, Zeldis J, Barlogie B, Tricot G. Source: The American Journal of Medicine. 2002 April 1; 112(5): 412-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904117

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IFN-alpha2b and thalidomide synergistically inhibit tumor-induced angiogenesis. Author(s): Bauer JA, Morrison BH, Grane RW, Jacobs BS, Borden EC, Lindner DJ. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2003 January; 23(1): 3-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639293

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Immune stimulation in scleroderma patients treated with thalidomide. Author(s): Oliver SJ, Moreira A, Kaplan G. Source: Clinical Immunology (Orlando, Fla.). 2000 November; 97(2): 109-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11027451

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Immunological effects of thalidomide and its chemical and functional analogs. Author(s): Dredge K, Marriott JB, Dalgleish AG. Source: Critical Reviews in Immunology. 2002; 22(5-6): 425-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803319

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Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Author(s): Lentzsch S, LeBlanc R, Podar K, Davies F, Lin B, Hideshima T, Catley L, Stirling DI, Anderson KC. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 January; 17(1): 41-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529658

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Immunomodulatory assays to study structure-activity relationships of thalidomide. Author(s): Shannon EJ, Morales MJ, Sandoval F. Source: Immunopharmacology. 1997 January; 35(3): 203-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043933

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Immunotherapeutic and antitumour potential of thalidomide analogues. Author(s): Marriott JB, Muller G, Stirling D, Dalgleish AG. Source: Expert Opinion on Biological Therapy. 2001 July; 1(4): 675-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11727503

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In vitro and in vivo kinetic interactions of the antitumour agent 5,6dimethylxanthenone-4-acetic acid with thalidomide and diclofenac. Author(s): Zhou S, Paxton JW, Kestell P, Tingle MD, Ching LM. Source: Cancer Chemotherapy and Pharmacology. 2001 April; 47(4): 319-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345648

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Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. Author(s): Bastuji-Garin S, Ochonisky S, Bouche P, Gherardi RK, Duguet C, Djerradine Z, Poli F, Revuz J; Thalidomide Neuropathy Study Group. Source: The Journal of Investigative Dermatology. 2002 November; 119(5): 1020-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445187

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Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer. Author(s): Horne MK 3rd, Figg WD, Arlen P, Gulley J, Parker C, Lakhani N, Parnes H, Dahut WL. Source: Pharmacotherapy. 2003 March; 23(3): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627929

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Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Author(s): Zangari M, Anaissie E, Barlogie B, Badros A, Desikan R, Gopal AV, Morris C, Toor A, Siegel E, Fink L, Tricot G. Source: Blood. 2001 September 1; 98(5): 1614-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520815

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Influence of thalidomide on Bcl2 expression and proangiogenic cytokine levels in short-term culture of peripheral blood and bone marrow mononuclear cells of multiple myeloma patients. Author(s): Dmoszynska A, Rolinski J, Bojarska-Junak A, Manko J, Jawniak D, WalterCroneck A, Soroka-Wojtaszko M, Hus M. Source: Polish Journal of Pharmacology. 2001 November-December; 53(6): 709-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11985351

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Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. Author(s): Keifer JA, Guttridge DC, Ashburner BP, Baldwin AS Jr. Source: The Journal of Biological Chemistry. 2001 June 22; 276(25): 22382-7. Epub 2001 April 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11297551

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Interferon alfa-2b three times daily and thalidomide in the treatment of metastatic renal cell carcinoma. Author(s): Hernberg M, Virkkunen P, Bono P, Ahtinen H, Maenpaa H, joensuu H. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 15; 21(20): 3770-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551295

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Intermediate dose thalidomide (200 mg daily) has comparable efficacy and less toxicity than higher doses in relapsed multiple myeloma. Author(s): Wechalekar AD, Chen CI, Sutton D, Reece D, Voralia M, Stewart AK. Source: Leukemia & Lymphoma. 2003 July; 44(7): 1147-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916866

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Intractable insomnia after cessation of treatment with thalidomide. Author(s): Fox MR, Harris A. Source: Gastroenterology. 2001 May; 120(6): 1567-8. Erratum In: Gastroenterology 2001 September; 121(3): 747. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11339241

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Intravenous formulations of the enantiomers of thalidomide: pharmacokinetic and initial pharmacodynamic characterization in man. Author(s): Eriksson T, Bjorkman S, Roth B, Hoglund P. Source: The Journal of Pharmacy and Pharmacology. 2000 July; 52(7): 807-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933131

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Irinotecan and thalidomide in metastatic colorectal cancer. Author(s): Govindarajan R. Source: Oncology (Huntingt). 2000 December; 14(12 Suppl 13): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204671

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Irinotecan/thalidomide in metastatic colorectal cancer. Author(s): Govindarajan R. Source: Oncology (Huntingt). 2002 April; 16(4 Suppl 3): 23-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12014864

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Is thalidomide a true anti-angiogenic molecule in multiple myeloma? Author(s): Ribatti D, Vacca A. Source: Haematologica. 2002 April; 87(4): 344-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940476

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Is thalidomide effective for the treatment of gastrointestinal bleeding in hereditary hemorrhagic telangiectasia? Author(s): Perez-Encinas M, Rabunal Martinez MJ, Bello Lopez JL. Source: Haematologica. 2002 August; 87(8): Elt34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161379

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Jekyll and Hyde: a new license for thalidomide? Author(s): Saphir A. Source: Journal of the National Cancer Institute. 1997 October 15; 89(20): 1480-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9337341

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Joint HOVON-50/GMMG-HD3 randomized trial on the effect of thalidomide as part of a high-dose therapy regimen and as maintenance treatment for newly diagnosed myeloma patients. Author(s): Goldschmidt H, Sonneveld P, Cremer FW, van der Holt B, Westveer P, Breitkreutz I, Benner A, Glasmacher A, Schmidt-Wolf IG, Martin H, Hoelzer D, Ho AD, Lokhorst HM; HOVON; GMMG. Source: Annals of Hematology. 2003 October; 82(10): 654-9. Epub 2003 July 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845480

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Lack of in vitro antimicrosporidian activity of thalidomide. Author(s): Ridoux O, Drancourt M. Source: Antimicrobial Agents and Chemotherapy. 1999 September; 43(9): 2305-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10471585

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Lack of response to thalidomide in plasmacytomas. Author(s): Myers B, Grimley C, Crouch D, Dolan G. Source: British Journal of Haematology. 2001 October; 115(1): 234. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11722443

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Licensing thalidomide in Australia. Author(s): Crawford CL. Source: The Medical Journal of Australia. 2004 February 16; 180(4): 199-200; Discussion 200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960148

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Lichen planopilaris treated with thalidomide. Author(s): George SJ, Hsu S. Source: Journal of the American Academy of Dermatology. 2001 December; 45(6): 965-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712051

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Life-threatening toxic epidermal necrolysis with thalidomide therapy for myeloma. Author(s): Rajkumar SV, Gertz MA, Witzig TE. Source: The New England Journal of Medicine. 2000 September 28; 343(13): 972-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11012329

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Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper-IgD and periodic fever syndrome: a randomized, double-blind, placebo-controlled trial. Author(s): Drenth JP, Vonk AG, Simon A, Powell R, van der Meer JW. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 September; 298(3): 1221-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11504824

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Living in a world with thalidomide: a dose of reality. Author(s): Warren R. Source: Fda Consumer. 2001 March-April; 35(2): 40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11444250

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Longitudinal limb deficiencies and the sclerotomes. An analysis of 378 dysmelic malformations induced by thalidomide. Author(s): McCredie J, Willert HG. Source: The Journal of Bone and Joint Surgery. British Volume. 1999 January; 81(1): 9-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10067994

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Long-term survival of a patient with small-cell lung cancer (SCLC) following treatment with thalidomide and combination chemotherapy. Author(s): Mall JW, Philipp AW, Mall W, Pollmann C. Source: Angiogenesis. 2002; 5(1-2): 11-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549855

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Long-term thalidomide for actinic prurigo. Author(s): Yong-Gee SA, Muir JB. Source: The Australasian Journal of Dermatology. 2001 November; 42(4): 281-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903163

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Low bioavailability of rectally administered thalidomide. Author(s): Eriksson T, Wallin R, Hoglund P, Roth B, Qi Z, Ostraat O, Bjorkman S. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 September 1; 57(17): 1607-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984814

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Low dose thalidomide in patients with relapsed or refractory multiple myeloma. Author(s): Kees M, Dimou G, Sillaber C, Drach J, Ackermann J, Lechner K, Gisslinger H. Source: Leukemia & Lymphoma. 2003 November; 44(11): 1943-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738147

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Low-dose of thalidomide in the treatment of refractory myeloma. Author(s): Pini M, Baraldi A, Pietrasanta D, Allione B, Depaoli L, Salvi F, Levis A. Source: Haematologica. 2000 October; 85(10): 1111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11025615

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Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial. Author(s): Marchetti M, Barosi G, Balestri F, Viarengo G, Gentili S, Barulli S, Demory JL, Ilariucci F, Volpe A, Bordessoule D, Grossi A, Le Bousse-Kerdiles MC, Caenazzo A, Pecci A, Falcone A, Broccia G, Bendotti C, Bauduer F, Buccisano F, Dupriez B. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 February 1; 22(3): 424-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752066

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Low-dose thalidomide in myeloma: efficacy and biologic significance. Author(s): Durie BG. Source: Seminars in Oncology. 2002 December; 29(6 Suppl 17): 34-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12520483

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Low-dose thalidomide is an effective second-line treatment in cutaneous lupus erythematosus. Author(s): Thomson KF, Goodfield MJ. Source: The Journal of Dermatological Treatment. 2001 September; 12(3): 145-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243705

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Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Author(s): Palumbo A, Giaccone L, Bertola A, Pregno P, Bringhen S, Rus C, Triolo S, Gallo E, Pileri A, Boccadoro M. Source: Haematologica. 2001 April; 86(4): 399-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11325646

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Low-dose thalidomide seems to be effective in multiple myeloma. Author(s): Larkin M. Source: Lancet. 1999 September 11; 354(9182): 925. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10489962

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Low-dose thalidomide therapy for refractory cutaneous lesions of lupus erythematosus. Author(s): Housman TS, Jorizzo JL, McCarty MA, Grummer SE, Fleischer AB Jr, Sutej PG. Source: Archives of Dermatology. 2003 January; 139(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533164

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Low-dose thalidomide treatment for advanced hepatocellular carcinoma. Author(s): Hsu C, Chen CN, Chen LT, Wu CY, Yang PM, Lai MY, Lee PH, Cheng AL. Source: Oncology. 2003; 65(3): 242-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657598

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Management of erythema nodosum leprosum by thalidomide: thalidomide analogues inhibit M. leprae-induced TNFalpha production in vitro. Author(s): Sampaio EP, Hernandez MO, Carvalho DS, Sarno EN. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002 February; 56(1): 13-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11905505

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Management of Kaposi sarcoma: the role of interferon and thalidomide. Author(s): Krown SE. Source: Current Opinion in Oncology. 2001 September; 13(5): 374-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555715

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Mechanism of action in thalidomide teratogenesis. Author(s): Stephens TD, Bunde CJ, Fillmore BJ. Source: Biochemical Pharmacology. 2000 June 15; 59(12): 1489-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10799645

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Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma. Author(s): D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS. Source: Seminars in Oncology. 2001 December; 28(6): 597-601. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740816

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Mechanism of teratogenic action of thalidomide. Author(s): Vaisman B. Source: Teratology. 1996 May; 53(5): 283-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8879085

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Mechanism of the teratogenic effect of thalidomide. Author(s): McCredie J. Source: Medical Hypotheses. 1976 March-April; 2(2): 63-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=947085

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Mechanisms of action and potential therapeutic uses of thalidomide. Author(s): Mujagic H, Chabner BA, Mujagic Z. Source: Croatian Medical Journal. 2002 June; 43(3): 274-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035132

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Mechanisms of thalidomide teratogenicity. Author(s): Guenzler V. Source: Nature Medicine. 1999 August; 5(8): 853. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10426292

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Medical and psychosocial aspects of the habilitation of thalidomide children. Author(s): Mongeau M, Gingras G, Sherman ED, Hebert B, Hutchison J, Corriveau C. Source: Can Med Assoc J. 1966 August 27; 95(9): 390-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5923651

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Metabolism of thalidomide in human microsomes, cloned human cytochrome P-450 isozymes, and Hansen's disease patients. Author(s): Teo SK, Sabourin PJ, O'Brien K, Kook KA, Thomas SD. Source: Journal of Biochemical and Molecular Toxicology. 2000; 14(3): 140-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10711629

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Minor ocular abnormalities associated with thalidomide. Author(s): Cant JS. Source: Lancet. 1966 May 21; 1(7447): 1134. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4160862

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Miscellaneous treatments: thalidomide, potassium iodide, levamisole, clofazimine, colchicine, and D-penicillamine. Author(s): Sanchez MR. Source: Clinics in Dermatology. 2000 January-February; 18(1): 131-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701095

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Mixed response to thalidomide therapy in adults: two cases of multisystem Langerhans' cell histiocytosis. Author(s): Kolde G, Schulze P, Sterry W. Source: Acta Dermato-Venereologica. 2002; 82(5): 384-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12430744

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Modifications to therapy for multiple myeloma: pegylated liposomal Doxorubicin in combination with vincristine, reduced-dose dexamethasone, and thalidomide. Author(s): Hussein MA. Source: The Oncologist. 2003; 8 Suppl 3: 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671227

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Modulation of LPS-, PHA- and M. tuberculosis-mediated cytokine production by pentoxifylline and thalidomide. Author(s): van Crevel R, Vonk AG, Netea MG, Kullberg BJ, van der Meer JW. Source: European Cytokine Network. 2000 December; 11(4): 574-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11125299

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Moebius syndrome associated with the mother taking thalidomide during gestation. Case report. Author(s): Elsahy NI. Source: Plastic and Reconstructive Surgery. 1973 January; 51(1): 93-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4687573

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Motor conduction velocity studies in patients with leprosy reaction treated with thalidomide and other drugs. Author(s): Sheskin J, Magora A, Sagher F. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 1969 October-December; 37(4): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4918201

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Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Author(s): Mileshkin L, Biagi JJ, Mitchell P, Underhill C, Grigg A, Bell R, McKendrick J, Briggs P, Seymour JF, Lillie K, Smith JG, Zeldis JB, Prince HM. Source: Blood. 2003 July 1; 102(1): 69-77. Epub 2003 March 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637329

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Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acrorenal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy. Author(s): Kohlhase J, Schubert L, Liebers M, Rauch A, Becker K, Mohammed SN, Newbury-Ecob R, Reardon W. Source: Journal of Medical Genetics. 2003 July; 40(7): 473-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843316

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Negligible clinical effects of thalidomide in patients with myelofibrosis with myeloid metaplasia. Author(s): Merup M, Kutti J, Birgergard G, Mauritzson N, Bjorkholm M, Markevarn B, Maim C, Westin J, Palmblad J; Swedish National Study Group on Chronic Myeloproliferative Disorders. Source: Medical Oncology (Northwood, London, England). 2002; 19(2): 79-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180484

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Never-ending tales of the mode of the teratogenic action of thalidomide. Author(s): Neubert D. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1997; 17(1): I-Ii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9249924

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New approaches in the treatment of metastatic melanoma: thalidomide and temozolomide. Author(s): Hwu WJ. Source: Oncology (Huntingt). 2000 December; 14(12 Suppl 13): 25-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204670

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New concerns about thalidomide. Author(s): Ances BM. Source: Obstetrics and Gynecology. 2002 January; 99(1): 125-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777522

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New insights into the pharmacological and toxicological effects of thalidomide. Author(s): Meierhofer C, Wiedermann CJ. Source: Curr Opin Drug Discov Devel. 2003 January; 6(1): 92-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613280

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New life in a sleeper: thalidomide and Crohn's disease. Author(s): Sands BE, Podolsky DK. Source: Gastroenterology. 1999 December; 117(6): 1485-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10579990

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New roles for thalidomide. Author(s): Powell RJ. Source: Bmj (Clinical Research Ed.). 1996 August 17; 313(7054): 377-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8761209

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New therapies for ankylosing spondylitis: etanercept, thalidomide, and pamidronate. Author(s): Davis JC Jr, Huang F, Maksymowych W. Source: Rheumatic Diseases Clinics of North America. 2003 August; 29(3): 481-94, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951863

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New therapies for heart failure: is thalidomide the answer? Author(s): Davey PP, Ashrafian H. Source: Qjm : Monthly Journal of the Association of Physicians. 2000 May; 93(5): 305-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10825407

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New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide. Author(s): Ravot E, Lisziewicz J, Lori F. Source: Drugs. 1999 December; 58(6): 953-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10651384

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Normal child after maternal thalidomide ingestion in critical period of pregnancy. Author(s): Pembrey ME, Clarke CA, Frais MM. Source: Lancet. 1970 February 7; 1(7641): 275-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4189295

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Novel biological response modifiers derived from thalidomide. Author(s): Hashimoto Y. Source: Current Medicinal Chemistry. 1998 June; 5(3): 163-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9562600

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Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Author(s): Dredge K, Marriott JB, Macdonald CD, Man HW, Chen R, Muller GW, Stirling D, Dalgleish AG. Source: British Journal of Cancer. 2002 November 4; 87(10): 1166-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402158

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Ocular findings in thalidomide children. Author(s): Rafuse EV, Arstikaitis M, Brent HP. Source: Can J Ophthalmol. 1967 July; 2(3): 222-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4962690

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Ocular malformations caused by thalidomide. Author(s): Zetterstrom B. Source: Acta Ophthalmol (Copenh). 1966; 44(3): 391-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4958479

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Ocular motility in thalidomide embryopathy. Author(s): Miller MT, Stromland K. Source: Journal of Pediatric Ophthalmology and Strabismus. 1991 January-February; 28(1): 47-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2019959

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Oesophageal cancer and cachexia: the effect of short-term treatment with thalidomide on weight loss and lean body mass. Author(s): Khan ZH, Simpson EJ, Cole AT, Holt M, MacDonald I, Pye D, Austin A, Freeman JG. Source: Alimentary Pharmacology & Therapeutics. 2003 March 1; 17(5): 677-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641516

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Offspring of male and female parents with thalidomide embryopathy: birth defects and functional anomalies. Author(s): Stromland K, Philipson E, Andersson Gronlund M. Source: Teratology. 2002 September; 66(3): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210472

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On thalidomide and WHO policies. Author(s): Pereira GF. Source: Lepr Rev. 2003 September; 74(3): 288-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14577478

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On the use of thalidomide as an antiangiogenic agent in the treatment of multiple myeloma. Author(s): Ribatti D, Vacca A. Source: Annals of Hematology. 2003 April; 82(4): 262. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707735

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One-year open-label trial of thalidomide in ankylosing spondylitis. Author(s): Huang F, Gu J, Zhao W, Zhu J, Zhang J, Yu DT. Source: Arthritis and Rheumatism. 2002 June 15; 47(3): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115153

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Oral lichenoid lesions after thalidomide treatment. Author(s): Bez C, Lodi G, Sardella A, Della Volpe A, Carrassi A. Source: Dermatology (Basel, Switzerland). 1999; 199(2): 195. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10559603

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Ovarian and papillary-serous peritoneal carcinoma: pilot study with thalidomide. Author(s): Abramson N, Stokes PK, Luke M, Marks AR, Harris JM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 February 15; 20(4): 1147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844842

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Ovarian failure with thalidomide treatment in complex aphthosis: comment on the concise communication by Ordi et al. Author(s): Gompel A, Frances C, Piette JC, Blanc AS, Cordoliani F, Piette AM. Source: Arthritis and Rheumatism. 1999 October; 42(10): 2259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10524707

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Pegylated-interferon induced severe bone marrow hypoplasia in a patient with multiple myeloma receiving thalidomide. Author(s): Gomez-Rangel JD, Ruiz-Delgado GJ, Ruiz-Arguelles GJ. Source: American Journal of Hematology. 2003 December; 74(4): 290-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635214

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Percutaneous delivery of thalidomide and its N-alkyl analogs. Author(s): Goosen C, Laing TJ, du Plessis J, Goosen TC, Lu GW, Flynn GL. Source: Pharmaceutical Research. 2002 April; 19(4): 434-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12033376

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Pharmacogenetic associations of CYP2C19 genotype with in vivo metabolisms and pharmacological effects of thalidomide. Author(s): Ando Y, Price DK, Dahut WL, Cox MC, Reed E, Figg WD. Source: Cancer Biology & Therapy. 2002 November-December; 1(6): 669-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12642692

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Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis. Author(s): Eriksson T, Hoglund P, Turesson I, Waage A, Don BR, Vu J, Scheffler M, Kaysen GA. Source: The Journal of Pharmacy and Pharmacology. 2003 December; 55(12): 1701-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738599

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Phase I study of thalidomide for the treatment of plexiform neurofibroma in neurofibromatosis 1. Author(s): Gupta A, Cohen BH, Ruggieri P, Packer RJ, Phillips PC. Source: Neurology. 2003 January 14; 60(1): 130-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525736

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Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Author(s): Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit H, Polychronis A, Pandha H, Muller GW, Stirling DI, Zeldis J, Dalgleish AG. Source: British Journal of Cancer. 2004 March 8; 90(5): 955-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997189

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Phase II evaluation of thalidomide in patients with metastatic breast cancer. Author(s): Baidas SM, Winer EP, Fleming GF, Harris L, Pluda JM, Crawford JG, Yamauchi H, Isaacs C, Hanfelt J, Tefft M, Flockhart D, Johnson MD, Hawkins MJ, Lippman ME, Hayes DF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 July; 18(14): 2710-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894870

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Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma. Author(s): Hwu WJ, Krown SE, Menell JH, Panageas KS, Merrell J, Lamb LA, Williams LJ, Quinn CJ, Foster T, Chapman PB, Livingston PO, Wolchok JD, Houghton AN. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3351-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947072

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Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas. Author(s): Fine HA, Wen PY, Maher EA, Viscosi E, Batchelor T, Lakhani N, Figg WD, Purow BW, Borkowf CB. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12805330

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Phase II trial of thalidomide for patients with advanced renal cell carcinoma. Author(s): Motzer RJ, Berg W, Ginsberg M, Russo P, Vuky J, Yu R, Bacik J, Mazumdar M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 January 1; 20(1): 302-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773183

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Phase II trial of thalidomide in renal-cell carcinoma. Author(s): Escudier B, Lassau N, Couanet D, Angevin E, Mesrati F, Leborgne S, Garofano A, Leboulaire C, Dupouy N, Laplanche A. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 July; 13(7): 1029-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176780

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Plasma levels of tumour necrosis factor alpha and interleukin-6 predict progressionfree survival following thalidomide therapy in patients with previously untreated multiple myeloma. Author(s): Thompson MA, Witzig TE, Kumar S, Timm MM, Haug J, Fonseca R, Greipp PR, Lust JA, Rajkumar SV. Source: British Journal of Haematology. 2003 October; 123(2): 305-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531913

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Polymorphisms of the tumor necrosis factor-alpha gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma. Author(s): Neben K, Mytilineos J, Moehler TM, Preiss A, Kraemer A, Ho AD, Opelz G, Goldschmidt H. Source: Blood. 2002 September 15; 100(6): 2263-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200397

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Potential novel uses of thalidomide: focus on palliative care. Author(s): Peuckmann V, Fisch M, Bruera E. Source: Drugs. 2000 August; 60(2): 273-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10983733

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Preclinical and clinical assessment of the safety and potential efficacy of thalidomide in heart failure. Author(s): Agoston I, Dibbs ZI, Wang F, Muller G, Zeldis JB, Mann DL, Bozkurt B. Source: Journal of Cardiac Failure. 2002 October; 8(5): 306-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12411981

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Predicting the dermal absorption of thalidomide and its derivatives. Author(s): Hadgraft J, Goosen C, du Plessis J, Flynn G. Source: Skin Pharmacology and Applied Skin Physiology. 2003 March-April; 16(2): 1239. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637788

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Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study. Author(s): Zervas K, Dimopoulos MA, Hatzicharissi E, Anagnostopoulos A, Papaioannou M, Mitsouli Ch, Panagiotidis P, Korantzis J, Tzilianos M, Maniatis A; Greek Myeloma Study Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 January; 15(1): 134-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679133

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Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma. Author(s): Dmoszynska A, Bojarska-Junak A, Domanski D, Rolinski J, Hus M, SorokaWojtaszko M. Source: Leukemia & Lymphoma. 2002 February; 43(2): 401-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999576

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PSA response to thalidomide in patients with advanced prostate cancer. Author(s): Leibowitz R, Tucker SJ. Source: Oncology (Huntingt). 2002 September; 16(9): 1146, 1148. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12380944

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Pulmonary toxicity during prostate cancer treatment with docetaxel and thalidomide. Author(s): Behrens RJ, Gulley JL, Dahut WL. Source: American Journal of Therapeutics. 2003 May-June; 10(3): 228-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756431

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Quantitative determination of thalidomide in human serum with high-performance liquid chromatography using protein precipitation with trichloroacetic acid and ultraviolet detection. Author(s): Torano JS, Verbon A, Guchelaar HJ. Source: J Chromatogr B Biomed Sci Appl. 1999 November 12; 734(2): 203-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10595718

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Question of toxicity of thalidomide in the treatment of leprosy reaction. Author(s): Berkeley JS. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 1968 October-December; 36(4): 457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5753816

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Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Author(s): Wolkenstein P, Latarjet J, Roujeau JC, Duguet C, Boudeau S, Vaillant L, Maignan M, Schuhmacher MH, Milpied B, Pilorget A, Bocquet H, Brun-Buisson C, Revuz J. Source: Lancet. 1998 November 14; 352(9140): 1586-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9843104

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Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease. Author(s): Arora M, Wagner JE, Davies SM, Blazar BR, Defor T, Enright H, Miller WJ, Weisdorf DF. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2001; 7(5): 265-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11400948

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Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. Author(s): Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, Lomax L, Ashcroft L, Thatcher N, Middleton MR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 1; 21(13): 2551-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829675

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Rasmussen syndrome and long-term response to thalidomide. Author(s): Marjanovic BD, Stojanov LM, Zdravkovic DS, Kravljanac RM, Djordjevic MS. Source: Pediatric Neurology. 2003 August; 29(2): 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580660

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Recalcitrant pyoderma gangrenosum treated with thalidomide. Author(s): Federman GL, Federman DG. Source: Mayo Clinic Proceedings. 2000 August; 75(8): 842-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10943240

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Recalcitrant pyoderma gangrenosum: treatment with thalidomide. Author(s): Hecker MS, Lebwohl MG. Source: Journal of the American Academy of Dermatology. 1998 March; 38(3): 490-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9520035

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Recent results of biotransformation of drugs: investigation of the in vitro biotransformation of thalidomide using a dual cyclodextrin system in capillary electrophoresis. Author(s): Blaschke G, Meyring M, Muhlenbrock C, Chankvetadze B. Source: Farmaco (Societa Chimica Italiana : 1989). 2002 July; 57(7): 551-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164212

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Recurrence of a choroidal neovascular membrane in a patient with punctate inner choroidopathy treated with daily doses of thalidomide. Author(s): Ip M, Gorin MB. Source: American Journal of Ophthalmology. 1996 October; 122(4): 594-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8862067

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Recurrent multicentric glioblastoma multiforme responds to thalidomide and chemotherapy. Author(s): Phuphanich S. Source: Oncology (Huntingt). 2002 March; 16(3): 276, 278. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046387

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Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. Author(s): Tseng S, Pak G, Washenik K, Pomeranz MK, Shupack JL. Source: Journal of the American Academy of Dermatology. 1996 December; 35(6): 96979. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8959957

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Reduction of leukocyte count is associated with thalidomide response in treatment of multiple myeloma. Author(s): Huang SY, Tang JL, Yao M, Ko BS, Hong RL, Tsai W, Wang CH, Tien HF, Shen MC, Chen YC. Source: Annals of Hematology. 2003 September; 82(9): 558-64. Epub 2003 July 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898185

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Renal cell carcinoma may adapt to and overcome anti-angiogenic intervention with thalidomide. Author(s): Douglas ML, Reid JL, Hii SI, Jonsson JR, Nicol DL. Source: Bju International. 2002 April; 89(6): 591-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11942970

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Research on thalidomide in solid tumors, hematologic malignancies, and supportive care. Author(s): Hussein MA. Source: Oncology (Huntingt). 2000 November; 14(11 Suppl 12): 9-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11125512

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Response rate, durability of response, and survival after thalidomide therapy for relapsed multiple myeloma. Author(s): Kumar S, Gertz MA, Dispenzieri A, Lacy MQ, Geyer SM, Iturria NL, Fonseca R, Hayman SR, Lust JA, Kyle RA, Greipp PR, Witzig TE, Rajkumar SV. Source: Mayo Clinic Proceedings. 2003 January; 78(1): 34-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528875

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Response to single-agent thalidomide and eligibility to undergo autotransplant for patients with multiple myeloma refractory to VAD. Author(s): Milone JH, Prates V, Bordone J, Napal J, Garcia C. Source: Bone Marrow Transplantation. 2003 August; 32(3): 343. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858210

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Response to thalidomide in chemotherapy-resistant mantle cell lymphoma: a case report. Author(s): Wilson EA, Jobanputra S, Jackson R, Parker AN, McQuaker IG. Source: British Journal of Haematology. 2002 October; 119(1): 128-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358916

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Response to thalidomide in progressive multiple myeloma is not mediated by inhibition of angiogenic cytokine secretion. Author(s): Neben K, Moehler T, Kraemer A, Benner A, Egerer G, Ho AD, Goldschmidt H. Source: British Journal of Haematology. 2001 December; 115(3): 605-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736942

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Response to thalidomide therapy in refractory chronic graft-versus-host disease. Author(s): Browne PV, Weisdorf DJ, DeFor T, Miller WJ, Davies SM, Filipovich A, McGlave PB, Ramsay NK, Wagner J, Enright H. Source: Bone Marrow Transplantation. 2000 October; 26(8): 865-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081386

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Reversible dementia due to thalidomide therapy for multiple myeloma. Author(s): Morgan AE, Smith WK, Levenson JL. Source: The New England Journal of Medicine. 2003 May 1; 348(18): 1821-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724497

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Reversible pulmonary hypertension and thalidomide therapy for multiple myeloma. Author(s): Younis TH, Alam A, Paplham P, Spangenthal E, McCarthy P. Source: British Journal of Haematology. 2003 April; 121(1): 191-2. Erratum In: Br J Haematol. 2003 November; 123(3): 563. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670354

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Safety, tolerability, and pharmacokinetic effects of thalidomide in patients infected with human immunodeficiency virus: AIDS Clinical Trials Group 267. Author(s): Wohl DA, Aweeka FT, Schmitz J, Pomerantz R, Cherng DW, Spritzler J, Fox L, Simpson D, Bell D, Holohan MK, Thomas S, Robinson W, Kaplan G, Teppler H; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group 267. Source: The Journal of Infectious Diseases. 2002 May 1; 185(9): 1359-63. Epub 2002 April 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001058

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Salvage therapy for hepatocellular carcinoma with thalidomide. Author(s): Wang TE, Kao CR, Lin SC, Chang WH, Chu CH, Lin J, Hsieh RK. Source: World Journal of Gastroenterology : Wjg. 2004 March 1; 10(5): 649-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991931

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Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma. Author(s): Tosi P, Zamagni E, Cellini C, Ronconi S, Patriarca F, Ballerini F, Musto P, Di Raimondo F, Ledda A, Lauria F, Masini L, Gobbi M, Vacca A, Ria R, Cangini D, Tura S, Baccarani M, Cavo M. Source: Haematologica. 2002 April; 87(4): 408-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940485

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Schnitzler's syndrome: successful treatment of two patients using thalidomide. Author(s): Worm M, Kolde G. Source: The British Journal of Dermatology. 2003 March; 148(3): 601-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653766

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Second response to lower-dose thalidomide in a patient with multiple myeloma. Author(s): Lee FC. Source: Blood. 2002 June 1; 99(11): 4248; Author Reply 4249. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12043696

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Sequential combination of thalidomide and erythropoietin determines transfusion independence and disease control in idiopathic myelofibrosis previously insensitive to both drugs used as single agents. Author(s): Visani G, Mele A, Malagola M, Isidori A, Finelli C, Piccaluga PP. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 August; 17(8): 1669-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886259

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Serum MUC-1 as a marker of disease status in multiple myeloma patients receiving thalidomide. Author(s): Mileshkin L, Prince HM, Seymour JF, Biagi JJ. Source: British Journal of Haematology. 2003 November; 123(4): 747-8; Author Reply 748. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616984

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Severe hepatic toxicity due to thalidomide in relapsed multiple myeloma. Author(s): Trojan A, Chasse E, Gay B, Pichert G, Taverna C. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 March; 14(3): 501-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598363

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Severe increase in creatinine with hypocalcaemia in thalidomide-treated myeloma patients receiving zoledronic acid infusions. Author(s): Jones SG, Dolan G, Lengyel K, Myers B. Source: British Journal of Haematology. 2002 November; 119(2): 576-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406106

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Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia. Author(s): Thomas DA, Estey E, Giles FJ, Faderl S, Cortes J, Keating M, O'Brien S, Albitar M, Kantarjian H. Source: British Journal of Haematology. 2003 November; 123(3): 436-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617002

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Solid-phase synthesis of thalidomide and its analogues. Author(s): Xiao Z, Schaefer K, Firestine S, Li PK. Source: Journal of Combinatorial Chemistry. 2002 March-April; 4(2): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886289

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Stabilization of a progressive hemangioblastoma under treatment with thalidomide. Author(s): Piribauer M, Czech T, Dieckmann K, Birner P, Hainfellner JA, Prayer D, Fazeny-Dorner B, Weinlander G, Marosi C. Source: Journal of Neuro-Oncology. 2004 February; 66(3): 295-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15015660

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Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human skin fibroblasts. Author(s): Nicolai S, Sies H, Stahl W. Source: Biochemical Pharmacology. 1997 May 15; 53(10): 1553-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9260883

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Structural development of biological response modifiers based on retinoids and thalidomide. Author(s): Hashimoto Y. Source: Mini Reviews in Medicinal Chemistry. 2002 December; 2(6): 543-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370039

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Successful treatment of a patient with HIV-associated multicentric Castleman disease (MCD) with thalidomide. Author(s): Jung CP, Emmerich B, Goebel FD, Bogner JR. Source: American Journal of Hematology. 2004 March; 75(3): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14978701

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Successful treatment of Behcet's syndrome in an African female patient with thalidomide. Author(s): Lewis DA, Amerasinghe CN, Murphy SM. Source: International Journal of Std & Aids. 1996 November-December; 7(7): 518-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9116070

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Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient. Author(s): Seyahi E, Ozdogan H, Masatlioglu S, Yazici H. Source: Clin Exp Rheumatol. 2002 July-August; 20(4 Suppl 26): S43-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371635

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Successful treatment of granulomatous cheilitis with thalidomide. Author(s): Thomas P, Walchner M, Ghoreschi K, Rocken M. Source: Archives of Dermatology. 2003 February; 139(2): 136-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588218

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Successful treatment of multiple myeloma relapsing after high-dose therapy and autologous transplantation with thalidomide as a single agent. Author(s): Zomas A, Anagnostopoulos N, Dimopoulos MA. Source: Bone Marrow Transplantation. 2000 June; 25(12): 1319-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10871741

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Successful treatment of muscle sarcoidosis with thalidomide. Author(s): Walter MC, Lochmuller H, Schlotter-Weigel B, Meindl T, Muller-Felber W. Source: Acta Myol. 2003 May; 22(1): 22-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12966701

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Thalidomide analogue CC-3052 reduces HIV+ neutrophil apoptosis in vitro. Author(s): Guckian M, Dransfield I, Hay P, Dalgleish AG. Source: Clinical and Experimental Immunology. 2000 September; 121(3): 472-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971513

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Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Author(s): Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, Treon SP, Lin B, Schlossman RL, Richardson P, Muller G, Stirling DI, Anderson KC. Source: Blood. 2000 November 1; 96(9): 2943-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11049970

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Thalidomide effectiveness for bilateral chronic idiopathic anterior uveitis in a threeyear-old child. Author(s): Parentin F, Da Pozzo S, Lepore L, Perissutti P. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2001 January-February; 215(1): 70-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11125274

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Thalidomide for the treatment of AIDS-associated wasting. Author(s): Kaplan G, Thomas S, Fierer DS, Mulligan K, Haslett PA, Fessel WJ, Smith LG, Kook KA, Stirling D, Schambelan M. Source: Aids Research and Human Retroviruses. 2000 September 20; 16(14): 1345-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11018854

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Thalidomide for treatment of patients with chronic graft-versus-host disease. Author(s): Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA, Sanders JE, Witherspoon RP, Appelbaum FR, Storb R, Martin PJ. Source: Blood. 2000 December 1; 96(12): 3995-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11090092

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Thalidomide in low intermittent doses does not prevent recurrence of human immunodeficiency virus-associated aphthous ulcers. Author(s): Jacobson JM, Greenspan JS, Spritzler J, Fox L, Fahey JL, Jackson JB, Chernoff M, Wohl DA, Pulvirenti JJ, Hooton TM, Shikuma C. Source: The Journal of Infectious Diseases. 2001 January 15; 183(2): 343-346. Epub 2000 December 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11120935

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Thalidomide in the treatment of cancer. Author(s): Adlard JW. Source: Anti-Cancer Drugs. 2000 November; 11(10): 787-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11142686

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Thalidomide in the treatment of high-grade gliomas. Author(s): Cohen MH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 October 1; 18(19): 3453. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11013292

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Thalidomide in the treatment of relapsed multiple myeloma. Author(s): Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Witzig TE, Kyle RA, Gertz MA, Greipp PR. Source: Mayo Clinic Proceedings. 2000 September; 75(9): 897-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10994824

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Thalidomide therapy in refractory solid tumour patients. Author(s): Gutheil J, Finucane D. Source: British Journal of Haematology. 2000 September; 110(3): 754. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997999

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Thalidomide treatment in advanced refractory myeloma. Author(s): Myers B, Crouch D, Dolan G. Source: British Journal of Haematology. 2000 December; 111(3): 986. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11122165

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Thalidomide. Author(s): Waldman AR. Source: Clinical Journal of Oncology Nursing. 2000 March-April; 4(2): 99-100. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11107384

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Thalidomide: a comeback? Author(s): Wendling D, Toussirot E, Michel F. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2000; 67(4): 259-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963070

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The re-emergence of thalidomide: results of a scientific conference. Author(s): Neiger BL. Source: Teratology. 2000 December; 62(6): 432-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11091366

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The Th1/Th2 paradigm in the pathogenesis of scleroderma, and its modulation by thalidomide. Author(s): Oliver SJ. Source: Curr Rheumatol Rep. 2000 December; 2(6): 486-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11123102

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The use of thalidomide in the management of severe sweating in patients with advanced malignancy: trial report. Author(s): Deaner PB. Source: Palliative Medicine. 2000 September; 14(5): 429-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11064791

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Unexpected toxicity of combination thalidomide and interferon alpha-2a treatment in metastatic renal cell carcinoma. Author(s): Nathan PD, Gore ME, Eisen TG. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 March 1; 20(5): 1429-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870194

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Update on therapy--thalidomide in the treatment of lupus. Author(s): Karim MY, Ruiz-Irastorza G, Khamashta MA, Hughes GR. Source: Lupus. 2001; 10(3): 188-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11315350

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Use of melphalan, thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma. Author(s): Srkalovic G, Elson P, Trebisky B, Karam MA, Hussein MA. Source: Medical Oncology (Northwood, London, England). 2002; 19(4): 219-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12512915

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Use of thalidomide for CGVHD defended. Author(s): Altomonte V. Source: Oncology Nursing Forum. 1993 April; 20(3): 428. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8497414

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Use of thalidomide in HIV infection. Author(s): Taiwo BO. Source: Aids Read. 2001 October; 11(10): 511-3, 518-9, 523-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11708084

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Use of thalidomide in leprosy. Author(s): Crawford CL. Source: Adverse Drug Reactions and Toxicological Reviews. 1994 Winter; 13(4): 177-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7734638

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Use of thalidomide in leprosy. Author(s): Hooper M. Source: Bmj (Clinical Research Ed.). 1991 November 30; 303(6814): 1404-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1760622

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Use of thalidomide in patients with myeloma and renal failure may be associated with unexplained hyperkalaemia. Author(s): Harris E, Behrens J, Samson D, Rahemtulla A, Russell NH, Byrne JL. Source: British Journal of Haematology. 2003 July; 122(1): 160-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823359

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Use of thalidomide in treatment and maintenance of idiopathic esophageal ulcers in HIV+ individuals. Author(s): Naum SM, Molloy PJ, Kania RJ, McGarr J, Van Thiel DH. Source: Digestive Diseases and Sciences. 1995 May; 40(5): 1147-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7729278

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Using thalidomide in a patient with epithelioid leiomyosarcoma and Osler-WeberRendu disease. Author(s): Kurstin R. Source: Oncology (Huntingt). 2002 January; 16(1): 21-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831608

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Vanishing corneal epithelial crystals following thalidomide induced resolution of myeloma related paraproteinaemia. Author(s): Shuttleworth GN, Cook SD, Ropner JE. Source: The British Journal of Ophthalmology. 2002 November; 86(11): 1315-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386099

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Venous thrombosis occurring after initiation of thalidomide for the treatment of cicatricial pemphigoid. Author(s): Howell E, Johnson SM. Source: J Drugs Dermatol. 2004 January-February; 3(1): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964754

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Warning: thalidomide-related thrombotic risk potentially concerns patients with lupus. Author(s): Piette JC, Sbai A, Frances C. Source: Lupus. 2002; 11(2): 67-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11958580

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Was the thalidomide tragedy preventable? Author(s): Critchley EM. Source: Lancet. 1998 May 23; 351(9115): 1591. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10326578

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Was the thalidomide tragedy preventable? Author(s): Smithells D. Source: Lancet. 1998 May 23; 351(9115): 1591. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10326577

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Was tumour necrosis factor-alpha responsible for the fetal malformations associated with thalidomide in the early 1960s? Author(s): Argiles JM, Carbo N, Lopez-Soriano FJ. Source: Medical Hypotheses. 1998 April; 50(4): 313-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9690766

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WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients. Author(s): Iyer CG, Languillon J, Ramanujam K, Tarabini-Castellani G, De las Aguas JT, Bechelli LM, Uemura K, Martinez Dominguez V, Sundaresan T. Source: Bulletin of the World Health Organization. 1971; 45(6): 719-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4947831

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Why I doubted that thalidomide was the cause of the epidemic of limb defects of 1959 to 1961. Author(s): Warkany J. Source: Teratology. 1988 September; 38(3): 217-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3227490

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

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

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

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

A looking glass perspective: thalidomide and cyclopamine. Author(s): Western Regional Research Center, ARS, USDA, Albany CA 94710, USA. [email protected] Source: Gaffield, W Incardona, J P Kapur, R P Roelink, H Cell-Mol-Biol-(Noisy-legrand). 1999 July; 45(5): 579-88 0145-5680

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A possible role of N-cadherin in thalidomide teratogenicity. Author(s): University of Leipzig, Institute of Zoology, Germany. [email protected] Source: Thiele, A Thormann, M Hofmann, H J Naumann, W W Eger, K Hauschildt, S Life-Sci. 2000 June 16; 67(4): 457-61 0024-3205

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Does thalidomide affect IL-2 response and production? Author(s): Bone Marrow Transplantation Program, Stanford University Medical Center, CA 94305, USA. Source: Fernandez, L P Schlegel, P G Baker, J Chen, Y Chao, N J Exp-Hematol. 1995 August; 23(9): 978-85 0301-472X

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Drug therapy in pregnancy: the lessons of diethylstilbestrol, thalidomide, and bendectin. Source: Saunders, E J Saunders, J A Health-Care-Women-Int. 1990; 11(4): 423-32 07399332

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Effect of thalidomide on the skeletal muscle in experimental heart failure. Author(s): Internal Medicine, Adria Hospital, Italy. [email protected] Source: Vescovo, G Ravara, B Angelini, A Sandri, M Carraro, U Ceconi, C Dalla Libera, L Eur-J-Heart-Fail. 2002 August; 4(4): 455-60 1388-9842

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Effects of oral thalidomide on rat liver and skin microsomal P450 isozyme activities and on urinary porphyrin excretion: interaction with oral hexachlorobenzene. Author(s): Department of Dermatology, University of Patras, Greece. Source: Tsambaos, D Bolsen, K Georgiou, S Monastirli, A Goerz, G Arch-Dermatol-Res. 1994; 286(6): 347-9 0340-3696

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Increased monoamine concentration in the brain and blood of fetal thalidomide- and valproic acid-exposed rat: putative animal models for autism. Author(s): Neurobiology Laboratory, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan. Source: Narita, N Kato, M Tazoe, M Miyazaki, K Narita, M Okado, N Pediatr-Res. 2002 October; 52(4): 576-9 0031-3998

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Induction of morphological differentiation in the human leukemic cell line K562 by exposure to thalidomide metabolites. Author(s): Radiotherapy Department, Faculty of Medicine, University of Stellenbosch, Tygerberg, R.S.A. Source: Hatfill, S J Fester, E D de Beer, D P Bohm, L Leuk-Res. 1991; 15(2-3): 129-36 01452126

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Influence of cyclodextrins on the in vitro corneal permeability and in vivo ocular distribution of thalidomide. Author(s): Klinge Pharma GmbH, Technological Development Laboratories, Munich, Germany. Source: Siefert, B Pleyer, U Muller, M Hartmann, C Keipert, S J-Ocul-Pharmacol-Ther. 1999 October; 15(5): 429-38 1080-7683

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Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity. Author(s): Auckland Cancer Society Research Centre, University of Auckland School of Medicine, New Zealand. Source: Ching, L M Browne, W L Tchernegovski, R Gregory, T Baguley, B C Palmer, B D Br-J-Cancer. 1998 August; 78(3): 336-43 0007-0920

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Mycoplasma fermentans-induced inflammatory response of astrocytes: selective modulation by aminoguanidine, thalidomide, pentoxifylline and IL-10. Author(s): The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Israel. Source: Gallily, R Kipper Galperin, M Brenner, T Inflammation. 1999 December; 23(6): 495-505 0360-3997

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Paclitaxel is more effective than thalidomide in inhibiting LNCaP tumor growth in a prostate cancer model. Author(s): Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, Illinois, USA. Source: Guinan, P Shaw, M Mirochnik, Y Slobodskoy, L Ray, V Rubenstein, M MethodsFind-Exp-Clin-Pharmacol. 1998 November; 20(9): 739-42 0379-0355

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Protective effect of pentoxifylline plus thalidomide against septic shock in mice. Author(s): Neuroimmunology Unit and Experimental Pathology Laboratory, Instituto Nacional de Neurologia y Neurocirugia and Universidad Nacional Autonoma de Mexico. [email protected] Source: Arrieta, O Ortiz Reyes, A Rembao, D Calvillo, M Rivera, E Sotelo, J Int-J-ExpPathol. 1999 February; 80(1): 11-6 0959-9673

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Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT. Author(s): Blood and Marrow Transplant Program, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263, USA. Source: Ahmad, I Islam, T Chanan Khan, A Hahn, T Wentling, D Becker, J L McCarthy, P L Jr Alam, A R Bone-Marrow-Transplant. 2002 April; 29(7): 577-80 0268-3369

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Thalidomide increases human keratinocyte migration and proliferation. Author(s): Dermatology Clinic, University of Catania, Italy. Source: Nasca, M R O'Toole, E A Palicharla, P West, D P Woodley, D T J-InvestDermatol. 1999 November; 113(5): 720-4 0022-202X

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Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia. Author(s): Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, USA. [email protected] Source: Badros, A Morris, C Zangari, M Barlogie, B Tricot, G Leuk-Lymphoma. 2002 June; 43(6): 1267-71 1042-8194

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Thalidomide responsive chronic pulmonary GVHD. Author(s): Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. Source: Forsyth, C J Cremer, P D Torzillo, P Iland, H J Young, G A Bone-MarrowTransplant. 1996 February; 17(2): 291-3 0268-3369

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Thalidomide suppresses NF-kappa B activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester. Author(s): Cytokine Research Laboratory, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Source: Majumdar, Sekhar Lamothe, Betty Aggarwal, Bharat B J-Immunol. 2002 March 15; 168(6): 2644-51 0022-1767

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The thalidomide analogue CC-3052 inhibits HIV-1 and tumour necrosis factor-alpha (TNF-alpha) expression in acutely and chronically infected cells in vitro. Author(s): Division of Hematology, IRCCS Ospedale Maggiore, Milan, Italy. Source: La Maestra, L Zaninoni, A Marriott, J B Lazzarin, A Dalgleish, A G Barcellini, W Clin-Exp-Immunol. 2000 January; 119(1): 123-9 0009-9104

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/

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 THALIDOMIDE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to thalidomide. 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 thalidomide 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 “thalidomide” (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 thalidomide: •

37th Annual American Society of Clinical Oncology Meeting. San Francisco, CA. May 12-15, 2001. Author(s): D'Orazio AI. Source: Clinical Lymphoma. 2001 June; 2(1): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712543

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A case of aggressive multiple myeloma with cleaved, multilobated, and monocytoid nuclei, and no serum monoclonal gammopathy. Author(s): Yeh YA, Pappas AA, Flick JT, Butch AW. Source: Ann Clin Lab Sci. 2000 July; 30(3): 283-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10945569

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A clinical study on severe hydroa vacciniforme. Author(s): Gu H, Chang B, Qian H, Li G.

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Source: Chinese Medical Journal. 1996 August; 109(8): 645-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9206069 •

A low toxicity maintenance regime, using eicosapentaenoic acid and readily available drugs, for mantle cell lymphoma and other malignancies with excess cyclin D1 levels. Author(s): Horrobin DF. Source: Medical Hypotheses. 2003 May; 60(5): 615-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12710892

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A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgenindependent prostate cancer. Author(s): Figg WD, Arlen P, Gulley J, Fernandez P, Noone M, Fedenko K, Hamilton M, Parker C, Kruger EA, Pluda J, Dahut WL. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 15): 62-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685731

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A review of the drug treatment of cachexia associated with cancer. Author(s): Gagnon B, Bruera E. Source: Drugs. 1998 May; 55(5): 675-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9585863

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'Accidental' anti-angiogenic drugs. anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples. Author(s): Kerbel RS, Viloria-Petit A, Klement G, Rak J. Source: European Journal of Cancer (Oxford, England : 1990). 2000 June; 36(10): 1248-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10882863

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Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications. Author(s): Zangari M, Saghafifar F, Anaissie E, Badros A, Desikan R, Fassas A, Mehta P, Morris C, Toor A, Whitfield D, Siegel E, Barlogie B, Fink L, Tricot G. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 April; 13(3): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943931

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Anecdotal therapies. Author(s): Millikan LE. Source: Advances in Experimental Medicine and Biology. 1999; 455: 407-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10599376

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Angiogenesis inhibitors in the treatment of lung cancer. Author(s): Shepherd FA. Source: Lung Cancer (Amsterdam, Netherlands). 2001 December; 34 Suppl 3: S81-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740999

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Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice. Author(s): Fujii T, Tachibana M, Dhar DK, Ueda S, Kinugasa S, Yoshimura H, Kohno H, Nagasue N. Source: Anticancer Res. 2003 May-June; 23(3B): 2405-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894521

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Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Author(s): Govindarajan R, Heaton KM, Broadwater R, Zeitlin A, Lang NP, HauerJensen M. Source: Lancet. 2000 August 12; 356(9229): 566-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950238

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Evaluation of the anti-tumor and anti-angiogenic effect of paclitaxel and thalidomide on the xenotransplanted oral squamous cell carcinoma. Author(s): Myoung H, Hong SD, Kim YY, Hong SP, Kim MJ. Source: Cancer Letters. 2001 February 26; 163(2): 191-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11165754

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Evaluation of the developmental toxicity of thalidomide using frog embryo teratogenesis assay-xenopus (FETAX): biotransformation and detoxification. Author(s): Fort DJ, Stover EL, Bantle JA, Finch RA. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 2000; 20(1): 35-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10607376

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Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer. Author(s): Horne MK 3rd, Figg WD, Arlen P, Gulley J, Parker C, Lakhani N, Parnes H, Dahut WL. Source: Pharmacotherapy. 2003 March; 23(3): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627929

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Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Author(s): Zangari M, Anaissie E, Barlogie B, Badros A, Desikan R, Gopal AV, Morris C, Toor A, Siegel E, Fink L, Tricot G.

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Source: Blood. 2001 September 1; 98(5): 1614-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520815 •

Irinotecan and thalidomide in metastatic colorectal cancer. Author(s): Govindarajan R. Source: Oncology (Huntingt). 2000 December; 14(12 Suppl 13): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204671

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Irinotecan/thalidomide in metastatic colorectal cancer. Author(s): Govindarajan R. Source: Oncology (Huntingt). 2002 April; 16(4 Suppl 3): 23-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12014864

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Low dose thalidomide in patients with relapsed or refractory multiple myeloma. Author(s): Kees M, Dimou G, Sillaber C, Drach J, Ackermann J, Lechner K, Gisslinger H. Source: Leukemia & Lymphoma. 2003 November; 44(11): 1943-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738147

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Modifications to therapy for multiple myeloma: pegylated liposomal Doxorubicin in combination with vincristine, reduced-dose dexamethasone, and thalidomide. Author(s): Hussein MA. Source: The Oncologist. 2003; 8 Suppl 3: 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671227

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Paclitaxel is more effective than thalidomide in inhibiting LNCaP tumor growth in a prostate cancer model. Author(s): Guinan P, Shaw M, Mirochnik Y, Slobodskoy L, Ray V, Rubenstein M. Source: Methods Find Exp Clin Pharmacol. 1998 November; 20(9): 739-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10022026

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Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study. Author(s): Zervas K, Dimopoulos MA, Hatzicharissi E, Anagnostopoulos A, Papaioannou M, Mitsouli Ch, Panagiotidis P, Korantzis J, Tzilianos M, Maniatis A; Greek Myeloma Study Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 January; 15(1): 134-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679133

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Pulmonary toxicity during prostate cancer treatment with docetaxel and thalidomide. Author(s): Behrens RJ, Gulley JL, Dahut WL.

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Source: American Journal of Therapeutics. 2003 May-June; 10(3): 228-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756431 •

Response to single-agent thalidomide and eligibility to undergo autotransplant for patients with multiple myeloma refractory to VAD. Author(s): Milone JH, Prates V, Bordone J, Napal J, Garcia C. Source: Bone Marrow Transplantation. 2003 August; 32(3): 343. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858210

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Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Author(s): Moehler TM, Neben K, Benner A, Egerer G, Krasniqi F, Ho AD, Goldschmidt H. Source: Blood. 2001 December 15; 98(13): 3846-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11739195

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Thalidomide and deep vein thrombosis in multiple myeloma: risk factors and effect on survival. Author(s): Zangari M, Barlogie B, Thertulien R, Jacobson J, Eddleman P, Fink L, Fassas A, Van Rhee F, Talamo G, Lee CK, Tricot G. Source: Clinical Lymphoma. 2003 June; 4(1): 32-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837152

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Thalidomide and irinotecan-associated diarrhea. Author(s): Tchekmedyian NS. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 June; 25(3): 324. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040298

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Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT. Author(s): Pitini V, Arrigo C, Aloi G, Micali C, La Gattuta G. Source: Bone Marrow Transplantation. 2003 June; 31(11): 1065; Author Reply 1067. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774062

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Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT. Author(s): Ahmad I, Islam T, Chanan-Khan A, Hahn T, Wentling D, Becker JL, McCarthy PL Jr, Alam AR. Source: Bone Marrow Transplantation. 2002 April; 29(7): 577-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11979306

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Thalidomide before autologous stem cell transplantation in VAD-refractory multiple myeloma patients. Author(s): Patriarca F, Sperotto A, Prosdocimo S, Geromin A, Zaja F, Fanin R. Source: Haematologica. 2003 May; 88(5): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745281

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Thalidomide may impede cell migration in primates by down-regulating integrin beta-chains: potential therapeutic utility in solid malignancies, proliferative retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis. Author(s): McCarty MF. Source: Medical Hypotheses. 1997 August; 49(2): 123-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9278924

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Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia. Author(s): Badros A, Morris C, Zangari M, Barlogie B, Tricot G. Source: Leukemia & Lymphoma. 2002 June; 43(6): 1267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12152995

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Thalidomide-associated hepatitis: a case report. Author(s): Fowler R, Imrie K. Source: American Journal of Hematology. 2001 April; 66(4): 300-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279644

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Thromboembolic events during treatment with thalidomide. Author(s): Urbauer E, Kaufmann H, Nosslinger T, Raderer M, Drach J. Source: Blood. 2002 June 1; 99(11): 4247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12043695

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Treatment of cutaneous sarcoidosis with thalidomide. Author(s): Nguyen YT, Dupuy A, Cordoliani F, Vignon-Pennamen MD, Lebbe C, Morel P, Rybojad M. Source: Journal of the American Academy of Dermatology. 2004 February; 50(2): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726878

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 thalidomide; 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 Macular Degeneration Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Lepidium Sp Alternative names: Cress; Lepidium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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

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CHAPTER 4. DISSERTATIONS ON THALIDOMIDE Overview In this chapter, we will give you a bibliography on recent dissertations relating to thalidomide. 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 “thalidomide” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on thalidomide, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Thalidomide 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 thalidomide. 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: •

Development of topical thalidomide for aphthous ulcers of HIV/AIDS patients by Gordon, Sharon Michelle; PhD from The Johns Hopkins University, 2003, 264 pages http://wwwlib.umi.com/dissertations/fullcit/3080669

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 THALIDOMIDE 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 “thalidomide” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on thalidomide, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Thalidomide By performing a patent search focusing on thalidomide, 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 thalidomide: •

Compounds analogous to thalidomide from the class comprising piperidine-2,6diones Inventor(s): Eger; Kurt (Tuebingen, DE), Teubert; Uwe (Oschatz, DE), Winter; Werner (Aachen, DE), Wnendt; Stephan (Aachen, DE), Zimmer; Oswald (Wuerselen, DE), Zwingenberger; Kai (Aachen, DE) Assignee(s): Gruenenthal Gmbh (Aachen, DE) Patent Number: 6,110,941 Date filed: January 29, 1998 Abstract: Compounds analogous to thalidomide from the class comprising piperidine2,6-diones are described, as are a method of preparing them and their use in drugs. Excerpt(s): This invention relates to compounds analogous to thalidomide from the class comprising piperidine-2,6-diones, to a method of preparing them, and to their use in drugs. The excessive formation of the cytokinin TNF-.alpha. (tumour necrosis factor.alpha.) plays a central part in the pathogenesis of graft-versus-host syndrome, of multiple sclerosis, or transplant rejection, aphthous stomatitis, erythema nodosum leprosum, morbus Boeck, rheumatoid arthritis and a series of other diseases which are associated with inflammatory symptoms. One basis for the therapy of these diseases consists of the targeted suppression of the release of TNF-.alpha. by administering immunosuppressant or immunomodulating active ingredients, such as dexamethasone, pentoxifylline or thalidomide for example. A distinction must be made, however, between indications which necessitate a general immunosuppression and those for which the advantages and disadvantages of immunosuppression have to be weighed up. In the treatment of aphthous stomatitis, thalidomide has been shown to be superior to classical immunosuppressants. Other examples of diseases in which thalidomide has exhibited good efficacy without resulting in a general immunosuppression include cutaneous lupus erythematosus (H+G 69, 816 to 822 (1994)), pyoderma gangrenosum and orogenital ulcers with morbus Behcet (The Lancet, 20.05.89, 1093 to 1095). The pathogenetic factors of these lesions, which are restricted to the skin and mucous membranes, are endogenous mediators which have effects on the endothelium and on circulating leukocytes. Under the influence of TNF-.alpha. and other cytokinins, there is a marked increase in the adhesiveness of the endothelium in relation to leukocytes, which makes a definitive contribution to the development of vasculitis. With systemic pathogens, the effect of thalidomide itself is restricted to the skin and mucous membranes, which necessitates (additional) immunosuppression. Examples thereof include systemic lupus erythematosus, which apart from dermal phenomena also causes life-threatening changes of the internal vessels, particularly of the kidneys; type II leprareaction, involving the eyes and/or the joints, as well as morbus Behget, involving the eyes and/or joints. Web site: http://www.delphion.com/details?pn=US06110941__

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Intravenous form of thalidomide for treating immunological diseases Inventor(s): Bjoerkman; Sven (Lund, SE), Eriksson; Tommy (Bjaerred, SE), Hoeglund; Peter (Klagstorp, SE) Assignee(s): Gruenenthal Gmbh (Aachen, DE) Patent Number: 6,124,322 Date filed: October 6, 1998 Abstract: An aqueous thalidomide solution which is suitable as a parenteral form of application of thalidomide, particularly as an intravenous form of application, for treating immunological diseases, and a method of producing the corresponding thalidomide solution. Excerpt(s): This invention relates to a parenteral form of application of thalidomide and to a method of producing it. The excessive formation of the cytokinin TNF-a (tumour necrosis factor a) plays a central part in the pathogenesis of graft-versus-host syndrome, aphthous stomatitis, erythema nodosum leprosum, morbus Boeck, morbus Crohn, rheumatoid arthritis and a series of other diseases which are associated with inflammatory symptoms. The basis for the therapy of these diseases consists of the targeted suppression of the release of TNF-a, by administering immunomodulating active ingredients, such as dexamethasone or thalidomide for example. While injectable forms of corticoids such as dexamethasone exist, this has hitherto not been the situation for thalidomide. In the treatment of aphthous stomatitis, thalidomide has been shown to be superior to classical immunosuppressants. Examples of diseases in which thalidomide has exhibited good efficacy without resulting in a general immunosuppression include cutaneous lupus erythematosus, pyoderma gangrenosum and orogenital ulcers with morbus Behcet, as well as ulcerations in HIV-infected patients, which do not differ histologically from aphthous ulcers and in which--in contrast to the majority of HIV-associated mucocutaneous lesions--no microbial instigators can be detected. As distinct from stomatitis aphthosa, these lesions, which can be characterized as major aphthae, can occur in the entire digestive tract, and when located in the pharyngeal space or the esophagus make the absorption of food difficult, and also make the taking of oral medication difficult, due to the pain which they cause. The pathogenetic factors are endogenous mediators which have effects on the endothelium and on circulating leukocytes. Under the influence of locally-formed TNF-a and other cytokinins, there is a marked increase in the adhesiveness of the endothelium in relation to leukocytes, which makes a definitive contribution to the development of venous vasculitis. Substances which, like thalidomide, suppress this alteration of the endothelium without at the same time blocking the specific cellular immune defense, can constitute an important advance in therapy. Web site: http://www.delphion.com/details?pn=US06124322__

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Method for treating neurocognitive disorders Inventor(s): Andrulis, Jr.; Peter J. (Bethesda, MD) Assignee(s): Andrulis Pharmaceuticals Corp. (Beltsville, MD) Patent Number: 5,434,170 Date filed: December 23, 1993

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Abstract: A method for treating a central nervous system or peripheral nervous system cholinergic deficit state in a mammalian organism in need of such treatment, said method comprising administering to said mammal an amount of thalidomide effective in the treatment of a cholinergic deficit state and for a time sufficient to achieve a suitable blood level to treat said cholinergic deficit state. Excerpt(s): The present invention is directed to compositions, and methods for alleviating the symptoms associated with neurocognitive disorders, i.e., senile dementia of the Alzheimer's type. In one specific aspect, the present invention is directed to a method for treating Alzheimer's disease with thalidomide. In another specific embodiment of the invention, senile dementia is treated with thalidomide in conjunction with nonsteroidal anti-inflammatory carboxylic acids selected from the group consisting of the aryl acetic acids, the aryl propionic acids, the salicylates, the ferramic acids, the biphenyl carboxylic acids and the diphenylether carboxylic acids. Thalidomide (N- phthalidoglutarimide) was first synthesized in 1953 by researchers at Chemie Grunenthal in Germany. It was marketed in Europe in 1956 as a sedative/hypnotic drug. Thalidomide is orally administered. It is poorly absorbed in humans. When 100 to 200 milligrams (mg) of thalidomide is ingested by humans, a maximal blood concentration of 0.9 to 1.5 mg/liter is attained 4 to 6 hours later. Thalidomide is extensively distributed throughout the body but does not selectively localize in any tissue. Thalidomide breaks down by spontaneous hydrolysis; however, the hydrolyric cleavage in serum is much slower than in vitro at pH 7.4. This may be due to thalidomide being highly bound to plasma proteins. Thalidomide metabolites are renally excreted. In a series of animal studies, racemic thalidomide has not been toxic. However, side effects in humans have included somnolence, teratogenicity and, upon extended administration, peripheral neuropathy. The teratogenic potential of thalidomide resulted in a variety of malformations of fetuses (phocomelia) and the subsequent removal of thalidomide from the market. The mechanism of the teratogenic effect is not known; however, it will occur when thalidomide is taken between the 35th and 50th day of the menstrual age of the embryo. Web site: http://www.delphion.com/details?pn=US05434170__ •

Methods and compositions for inhibition of angiogenesis Inventor(s): D'Amato; Robert (Lancaster, PA) Assignee(s): The Children's Medical Center Corporation (Boston, MA) Patent Number: 5,593,990 Date filed: January 13, 1995 Abstract: The present invention comprises a group of compounds that effectively inhibit angiogenesis. More specifically, thalidomide and various related compounds such as thalidomide precursors, analogs, metabolites and hydrolysis products have been shown to inhibit angiogenesis and to treat disease states resulting from angiogenesis. Importantly, these compounds can be administered orally. Excerpt(s): The present invention relates to methods and compositions for preventing unwanted angiogenesis in a human or animal. More particularly, the present invention relates to a method for preventing unwanted angiogenesis, particularly in angiogenesis dependent or associated diseases, by administration of compounds such as thalidomide and related compounds. As used herein, the term "angiogenesis" means the generation of new blood vessels into a tissue or organ. Under normal physiological conditions,

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humans or animals only undergo angiogenesis in very specific restricted situations. For example, angiogenesis is normally observed in wound healing, fetal and embryonal development and formation of the corpus luteum, endometrium and placenta. The control of angiogenesis is a highly regulated system of angiogenic stimulators and inhibitors. The control of angiogenesis has been found to be altered in certain disease states and, in many cases, the pathological damage associated with the disease is related to the uncontrolled angiogenesis. Both controlled and uncontrolled angiogenesis are thought to proceed in a similar manner. Endothelial cells and pericytes, surrounded by a basement membrane, form capillary blood vessels. Angiogenesis begins with the erosion of the basement membrane by enzymes released by endothelial cells and leukocytes. The endothelial cells, which line the lumen of blood vessels, then protrude through the basement membrane. Angiogenic stimulants induce the endothelial cells to migrate through the eroded basement membrane. The migrating cells form a "sprout" off the parent blood vessel, where the endothelial cells undergo mitosis and proliferate. The endothelial sprouts merge with each other to form capillary loops, creating the new blood vessel. In the disease state, prevention of angiogenesis could avert the damage caused by the invasion of the new microvascular system. Web site: http://www.delphion.com/details?pn=US05593990__ •

Pharmaceutical composition Inventor(s): Artmann; Carl (Gauting, DE), Regenold; Juergen (Ebringen, DE), Roeding; Joachim (Badenweiler, DE) Assignee(s): Mika Pharma Gesellschaft Fuer Die Entwicklung Und Vermarktung (Limburgerhof, DE) Patent Number: 5,958,379 Date filed: May 27, 1997 Abstract: A pharmaceutical composition containing at least one systemically and/or locally effective, topically applicable active substance, preferably selected from the group consisting of local anaesthetics, anti-allergic agents, dermatics, active substances for influenzal infections and colds, active substance for the treatment of neuropathies, chemotherapeutics, quinine, thalidomide, analgesics, non-steroid antirheumatics, opiate receptor agonists, opiate receptor antagonists, substances inhibiting the blood coagulation, substances inhibiting platelet aggregation, corticoids, histamine antagonists, anti-diabetics, regulatory peptides and the inhibitors thereof, prostaglandins and/or the esters thereof and/or antivirally effective substances is described. The pharmaceutical composition has such a liquid consistency that it is sprayable in droplets, and that after being sprayed the composition forms a preparation within short time, preferably within a time of less than 4 seconds, on the sprayed body surface, particularly on the sprayed skin or mucous membrane, whereby, compared to the original liquid composition, this preparation is formed in such a preparation which has an essentially higher concentration of the active substance and which contains the active substance in a finely divided way. Excerpt(s): The present invention is directed to a pharmaceutical composition with the characteristics of the generic part of patent claim 1. Pharmaceutical compositions with the active substance mentioned in the main claim are usually formed as injectable composition or as tablets, dragees or suppositories, in order to guarantee that way that the respective active substance is transported to the site of action within a very short time by means of the corresponding body liquid, particularly by means of the blood, in

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order to systemically cause the desired effect. Only in a few exceptional cases the active substances mentioned in the main claim are formed in the way that they can be topically applied, whereby such an application is suitable preferably for a local application, meaning for the locally limited external treatment. Rheumatic ointments with nonsteroid anti-rheumatics or heparin-containing ointments or creams are for example known which, however, are locally applied to the infected body zones where they effect in a regionally limited way. Web site: http://www.delphion.com/details?pn=US05958379__ •

Prevention of adhesions and excessive scar formation using angiogenesis inhibitors Inventor(s): Brem; Harold (300 E. 93rd St., Apt. 41C, New York, NY 10128), Ehrlich; H. Paul (995 Jonestown Rd., P.O. Box 545, Grantville, PA 17028), Folkman; Judah (18 Chatham Cir., Brookline, MA 02146) Assignee(s): None Reported Patent Number: 6,638,949 Date filed: August 25, 1998 Abstract: A method and compositions for inhibiting excessive scar formation and adhesions by administering to a patient in need thereof an effective amount of an angiogenesis inhibitor. In the preferred embodiment, the angiogenesis inhibitor is selective, such as a fumagillol derivative like 0-chloroacetylcarbamoyl-Fumagillol (TNP470, TAP Pharmaceuticals), thalidomide, or a selective drug having more than one activity, such as minocycline or penicilliamine which also have antibiotic activity. Less selective compounds can also be used, such as the cytokine IL12. Patients to be treated include those having experienced trauma, surgical intervention, burns, and other types of injuries. The inhibitor is administered in an amount effective to decrease excessive scarring, defined as formation of high density tissue including cells and connective tissue, without preventing normal wound closure. The inhibitors can be administered systemically and/or locally or topically, as needed. For prevention of adhesions, the angiogenesis inhibitor would typically be applied at the time of surgery, preferably in a controlled release formulation and/or using barrier technology. Excerpt(s): The present invention relates to methods for the prevention of adhesions, excessive scar formation and other types of abnormal proliferation of tissue using angiogenesis inhibitors. Scars are the result of wounds that have healed, lesions due to diseases, or surgical operations. Hypertrophic and keloid scars occur when the tissue response is out of proportion to the amount of scar tissue required for normal repair and healing. A keloid scar is a raised, firm, thickened red scar that exceeds the boundary of the injury and may grow for a prolonged period of time. The increase in scar size is due to deposition of all increased amount of collagen into the tissue. African-Americans are genetically prone to developing keloids. Keloid development has been associated with different types of skin injury including surgery, ear piercing, laceration, burns, vaccination or inflammatory process. Common sites are earlobes and the upper trunk and extremities. Surgical removal of keloids alone has been associated with a recurrence rate of 45% to 100%. The problem of excessive scar formation that manifests itself clinically is a multi-billion dollar problem. For example, intra-abdominal adhesions results in a very significant morbidity and mortality in every surgery practice. Greater than 400,000 hospital admissions in the United States per year are for treatment of pelvic adhesions following surgery. Repeat surgery can greatly aggravate scarring.

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Web site: http://www.delphion.com/details?pn=US06638949__ •

Topical thalidomide compositions for surface of mucosal wounds, ulcerations, and lesions Inventor(s): Piacquadio; Daniel J. (4262 Altamarino Way, San Diego, CA 92103) Assignee(s): None Reported Patent Number: 5,605,684 Date filed: June 7, 1995 Abstract: Surface wounds, inflammatory disorders, ophthalmic, mucosal, conjunctiva or other ocular disorders, ulcerations and lesions are treated with a solubilized or suspended topical composition containing as its active thalidomide or a pro drug, analog or biologically active salt form thereof. Excerpt(s): The present invention relates to a new use for a known compound, thalidomide. Thalidomide has been known as a tranquilizer since the late 1950's. The compound thalidomide was patented in Keller, U.S. Pat. No. 2,830,991 issued Apr. 15, 1958. It has the chemical name 3-phthalimido-piperidine dione 2,6. Thalidomide is a derivative of glutamic acid. As is well known, thalidomide was widely used in the early 1960's as a tranquilizer in Europe, although never approved for use in the United States. When it was discovered that even small amounts of thalidomide when taken by pregnant women caused birth defects, the drug was rapidly withdrawn from the market. As a result, thalidomide was never approved for use in the United States. Since that period in the early 1960's researchers have found that thalidomide is useful in treating inflammation associated with severe cases of erythema nodosum leprosum (ENL) leprosy. There is also literature indicating that the drug is useful in treating inflammatory processes associated with for example Lupus, see Lo, et al., treatment of discoid Lupus erythematosus, International Journal of Dermatology, October 1989 Vol. 29, No. 8, p. 497-507. At this point it is beyond question that thalidomide when taken by pregnant women is a teratogen; however, the fact remains that sufficient scientific evidence exists to merit its investigation for uses in environments in which it will not have the opportunity to function as a teratogenic agent. For example, thalidomide is now widely used in treatment of leprosy in situations where there is no risk to females of child bearing potential. Web site: http://www.delphion.com/details?pn=US05605684__

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Treatment of cancer with thalidomide alone or in combination with other anti-cancer agents Inventor(s): Andrulis, Jr.; Peter J. (Bethesda, MD), Drulak; Murray W. (Gaithersburg, MD) Assignee(s): Andrulis Pharmaceuticals Corp. (Bethesda, MD) Patent Number: 6,140,346 Date filed: May 4, 1998 Abstract: A method is provided for the treatment of neoplastic diseases in a mammal which comprises administering to said mammal a therapeutically effective amount of thalidomide. The method also uses a combination of thalidomide with other anti-

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neoplastic agents. Additionally, pharmaceutical compositions containing thalidomide and other anti-cancer agents are also provided. Excerpt(s): The present invention relates to a novel method for treating cancers with thalidomide alone or in combination with other antiangiogenic and anti-cancer agents. The present invention also relates to methods of treating cancers with cytokine/growth factor inhibitors such as those agents inhibitory to basic fibroblast growth factor (bFGF), Tumor Necrosis Factor alpha (TNF-alpha), and interleukin 1 beta (IL-1 beta) and other antiangiogenic agents as well as pharmaceutical compositions containing thalidomide and/or other antiangiogenesis agents and/or anticancer drugs. The present invention further relates to a method for ameliorating the symptoms of neoplastic diseases by administering thalidomide alone or in combination with other anti-neoplastic drugs. The instant invention also relates to a method for inhibiting establishment of neoplastic metastasis by administering thalidomide alone or in combination with other antineoplastic drugs. Web site: http://www.delphion.com/details?pn=US06140346__ •

Treatment of inflammatory and/or autoimmune dermatoses with thalidomide alone or in combination with other agents Inventor(s): Andrulis, Jr.; Peter J. (Bethesda, MD), Drulak; Murray W. (Gaithersburg, MD) Assignee(s): Andrulis Pharmaceuticals (Beltsville, MD) Patent Number: 5,654,312 Date filed: June 7, 1995 Abstract: Methods of treatment for inflammatory and autoimmune dermatoses which comprises topical and/or systemic administration of a therapeutically-effective amount of thalidomide alone or in combination with other dermatological agents. Excerpt(s): The present invention relates to novel methods for treating inflammatory and/or autoimmune dermatoses with thalidomide alone or in combination with other agents. The present invention also relates to methods of treating dermatoses with inhibitors of cytokine and/or growth factors such as those agents inhibitory to basic fibroblast growth factor (bFGF), Tumor Necrosis Factor (TNF-alpha), and Interleukin-1 beta (IL-1 beta) as well as pharmaceutical compositions containing relevant cytokine/growth factor inhibitors and/or other drug used to treat dermatoses. Inflammatory dermatoses describe a group of diseases involving the layers of skin below the epidermis that have an inflammatory component. Inflammation may be triggered by a number of external events ranging from exposure to UV light from the sun to an allergen. Thalidomide has been demonstrated to have an inhibitory effect on the pro-inflammatory cytokines. It has been shown to inhibit TNF-alpha production in erythema nodosum leprosum patients (Sarno et al., Clin. Exp. Immunol, 84:103-8, 1991) and in vitro stimulated monocytes (Sampaio et al., J. Exp. Med., 173:699-703, 1991). Moreira et al. (J. Exp. Med., 177:1675-80, 1993) reported that thalidomide acts by enhancing TNF-alpha m-RNA degradation. Shannon et al. (Amer. Society for Microbiology Ann. Mtg., Abs. U-53, 1990) indicated thalidomide inhibited IL-1 beta production in vitro. Such an inhibitory effect on IL-1 beta may be direct or indirect through TNF-alpha as suggested by Moreira et al. (1993). In 1965 Sheskin (Lepr. Rev., 36:183-7) administered thalidomide to leprosy patients suffering from the complication erythema nodosum leprosum (ENL), to sedate them. ENL is characterized by recurrent

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erythematosus nodules on the skin, weight loss, mania, neuritis, fever, malaise, and sometimes epididyo-orchitis. Within 12 hours of thalidomide administration nodular eruptions began to heal and within two days fever declined and the ENL lesions had completely resolved. In 1971 lyer et al., Bull. WHO, 45:719-32, presented the results of a double blind clinical trial conducted in four countries and coordinated by the World Health Organization, which tested the efficacy of thalidomide versus aspirin for treatment of ENL. The conclusions reached supported Sheskin's original observations about the effectiveness of thalidomide for treatment of ENL. Wemambu et al. (Lancet, 2:933-5, 1969) observed necrotizing vasculitis of veins and arteries in patients with ENL. This was accompanied by initial neutrophil accumulation at disease sites as well as deposits of complement and immunoglobulin. This description of the disease process in ENL is consistent with that of an Arthus Reaction. However, others in the field disputed this explanation for ENL pathogenesis. Goihman-Yahr et al., Int. Arch. Allergy Appl. Immun., 57:317-332 (1978) showed in a study of neutrophil activation in ENL patients just before and during treatment with thalidomide that tissue damage was not due solely to neutrophil activation as occurs in immune complex diseases, but rather neutrophils appeared to be activated by an undefined lymphokine. This group went on to state that the therapeutic effect of thalidomide was not due to inhibition of neutrophil activation. Sarno et al. (Clin. Exp. Immunol., 84:103-8, 1991) showed that TNF-alpha levels were elevated in ENL patients and that TNF-alpha had a major role in the pathogenesis of this disease. Thalidomide was shown to inhibit TNF-alpha production in these ENL patients. Sampaio et al. (J. Inf. Dis., 168:408-14, 1993) confirmed Sarno's results as to the inhibitory effect of thalidbmide on serum TNF-alpha levels, but also demonstrated a reduction of dermal infiltration of polymorphonuclear leukocytes and T cells. Web site: http://www.delphion.com/details?pn=US05654312__ •

Treatment of insulin resistant diabetes with thalidomine Inventor(s): Andrulis, Jr.; Peter J. (Bethesda, MD) Assignee(s): Andrulis Pharmaceuticals Corp. (Beltsville, MD) Patent Number: 5,405,855 Date filed: December 23, 1993 Abstract: A method for treating insulin-resistant diabetes in mammals which comprises administering to said afflicted animals a prophylactically or therapeutically effective amount of thalidomide. Excerpt(s): The present invention relates to a novel method for treating insulin-resistant diabetes in obese animals with a therapeutically effective amount of thalidomide. The disease diabetes mellitus is characterized by metabolic defects in the production and utilization of glucose which result in the failure to maintain appropriate blood sugar levels. The result of this defect is elevated blood glucose or hyperglycemia. Research on the treatment of diabetes has centered on attempts to normalize fasting and postpromdial blood glucose levels. Treatments have included parenteral administration of exogenous insulin, oral administration of drugs, and dietary therapies. Initially it was thought that hyperglycemia was simply the result of a deficiency in the supply of insulin, the key hormone which controls glucose metabolism. As a result, research focused on the source of insulin production, the beta cells of the pancreas, and pharmaceutical agents were discovered which stimulated the production of insulin by the pancreas. Although it remains true that a deficiency of insulin does cause

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hyperglycemia, it has now been recognized that other metabolic defects can be a major cause of elevated blood glucose. Web site: http://www.delphion.com/details?pn=US05405855__ •

Treatment of ischemia/reperfusion injury with thalidomide alone or in combination with other therapies Inventor(s): Andrulis, Jr.; Peter J. (Bethesda, MD), Drulak; Murray W. (Gaithersburg, MD) Assignee(s): Andrulis Pharmaceuticals Corp. (Beltsville, MD) Patent Number: 5,643,915 Date filed: June 6, 1995 Abstract: In accordance with the present invention, a method is provided for treating reperfusion injury, ischemia and runaway inflammatory conditions with thalidomide alone or in combination with other drugs selected from the group consisting of nitrates, beta-adrenoceptor blocking agents, anti-platelet/thrombolytic drugs, drugs acting as the arachindonic acid cascade and calcium antagonists. Pharmaceutical compositions comprising thalidomide alone or in combination with other drugs are also provided. Excerpt(s): The present invention generally relates to preventing or ameliorating tissue damage that occurs during ischemia/reperfusion conditions involving cytokine, growth factor and chemotactic cascades which arise during these severe inflammatory conditions. More particularly, the invention is related to the use of thalidomide as a therapeutic and/or protective agent in conditions characterized by ischemia/reperfusion such as acute myocardial infarction, stroke, spinal cord injury, head injury, severe infectious disease, inflammatory bowel conditions, cancer, and certain surgical procedures. The present invention further relates more generally to the protection of or inhibition of damage to various types of tissue whenever the inflammatory condition involves the damaging effects of oxygen free radicals and oxygen intermediates, and cytokines and growth factors which are involved in "runaway" inflammatory conditions. Hence the invention also relates to methods of treating various tissue types from mammalian species against the damaging effects of singlet oxygen, hydroxyl radical, cytokines and growth factors using thalidomide. The invention also relates to methods for improving post-ischemic myocardial and neuronal tissue functions in mammalian species by administering thalidomide and derivatives thereof. Web site: http://www.delphion.com/details?pn=US05643915__

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Treatment of melanomas with thalidomide alone or in combination with other antimelanoma agents Inventor(s): Andrulis, Jr.; Peter J. (Bethesda, MD), Drulak; Murray W. (Gaithersburg, MD) Assignee(s): Andrulis Pharmaceuticals Corp. (Bethesda, MD) Patent Number: 5,731,325 Date filed: June 6, 1995

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Abstract: A method for treatment of malignant melanoma by administering an effective amount of thalidomide alone or in combination with other anti-melanoma drugs. Excerpt(s): The present invention is directed to compositions and methods for treating malignant melanoma. In one specific aspect, the present invention is directed to a method for treating melanomas with thalidomide. In another specific embodiment of the invention, melanoma is treated with thalidomide in combination with other antimelanoma drugs. The present invention also relates to methods of treating melanomas with cytokine/growth factor inhibitors such as those agents inhibitory to basic fibroblast growth factor (bFGF), TNF-alpha, IL-1 and/or melanoma growth stimulatory activity (MGSA) factor as well as pharmaceutical compositions containing relevant cytokine/growth factor inhibitors and/or other anti-melanoma drugs. Thalidomide was first synthesized and marketed in the 1950's as a sedative. The toxicity of the compound was so low that a dose killing 50% of animals (LD.sub.50) could not be established. Thalidomide was therefore thought to be a safer alternative to barbiturates. In 1961, thalidomide administered to pregnant women resulted in an epidemic of congenial malformations. The incidence of malformed babies paralleled the sales of thalidomide and quickly dropped off when thalidomide was removed from the market. Web site: http://www.delphion.com/details?pn=US05731325__

Patent Applications on Thalidomide 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 thalidomide: •

Analogs of thalidomide as potential angiogenesis inhibitors Inventor(s): Eger, Kurt; (Leipzig, DE), Figg, William D.; (Fairfax, VA), Guetschow, Michael; (Bonn, DE), Hauschildt, Sunna; (Leipzig, DE), Hecker, Thomas; (Erfurt, DE), Teubert, Uwe; (Hameln, DE), Weiss, Michael; (Bethesda, MD) Correspondence: Klarquist Sparkman, Llp; 121 S.W. Salmon Street, Suite #1600; One World Trade Center; Portland; OR; 97204-2988; US Patent Application Number: 20040077685 Date filed: November 14, 2003 Abstract: A number of thalidomide metabolites having superior anti-angiogenic properties have now been isolated and identified In addition, thalidomide analogs that mimic the effects of the isolated and identified active thalidomide metabolites, and variations of such thalidomide analogs, have been developed. Such thalidomide analog compounds show enhanced potency in the inhibition of undesirable angiogenesis without the undesirable effects of administration of thalidomide. Excerpt(s): The present invention concerns anti-angiogenesis compositions and methods, and particularly thalidomide analogs that actively inhibit angiogenesis in humans and animals. Angiogenesis is the formation of new blood vessels from preexisting vessels. Angiogenesis is prominent in solid tumor formation and metastasis. A tumor requires formation of a network of blood vessels to sustain the nutrient and

9

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

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oxygen supply for continued growth. Some tumors in which angiogenesis is important include most solid tumors and benign tumors, such as acoustic neuroma, neurofibroma, trachoma, and pyogenic granulomas. Prevention of angiogenesis could halt the growth of these tumors and the resultant damage due to the presence of the tumor. It has been shown that there is a direct correlation between tumor microvessel density and the incidence of metastasis. Tumor cells themselves can produce factors that stimulate the proliferation of endothelial cells and new capillary growth. Angiogenesis is important in two stages of tumor metastasis. The first stage where angiogenesis stimulation is important is in the vascularization of the tumor, which allows tumor cells to enter the blood stream and to circulate throughout the body. After the tumor cells have left the primary site, and have settled into the secondary, metastasis site, angiogenesis must occur before the new tumor can grow and expand. Therefore, prevention of angiogenesis could lead to the prevention of metastasis of tumors and possibly contain the neoplastic growth at the primary site. These observations have led to the investigation of anti-angiogenic agents as possible therapeutic options for various cancers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for locally treating inflammatory diseases Inventor(s): Flynn, Gordon L.; (Ann Arbor, MI), Laing, Timothy J.; (Ann Arbor, MI) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20010041716 Date filed: December 1, 2000 Abstract: Compositions and methods are provided for treating inflammatory diseases in mammals by inhibiting TNF.alpha. expression. The methods comprise the step of topically administrating a composition of the present invention comprising thalidomide, N-alkyl analogs of thalidomide and combinations thereof. Excerpt(s): The present invention relates generally to compositions and methods for locally treating inflammatory diseases and, more particularly, to compositions and methods for treating inflammatory diseases by percutaneous delivery of thalidomide and analogs thereof. Thalidomide is a piperidinedione immunomodulator and is derived from a natural endogenous.alpha.-amino acid (glutamic acid). It is described as a N-phthaloyl-glutamic acid imide, and the chemical name is a-phthalimidoglutarimide. It was developed in the 1950's as the first example of a new class of non-barbiturate sedatives. Unfortunately, it was found to cause birth defects in infants born to women who had taken thalidomide during pregnancy. It was withdrawn from the market in 1961, but still remained available in certain countries for research purposes. Subsequently, and despite its history, thalidomide has been found to be beneficial in treating more than 20 different diseases including leprosy, tuberculosis, AIDS and various autoimmune diseases (Stirling, D. et al., Journal Of The American Pharmaceutical Association NS37:307-313 (1997)). In addition, thalidomide is currently used world-wide for the treatment of Bechet's disease and is the single most effective agent against erythema nodosum leprosum (ENL), a severe inflammatory skin condition associated with leprosy, (Sheskin, J., Clinical Pharmacology And Therapeutics 6:303-306 (1965)). It was only recently that thalidomide's probable mechanism of action in ENL was uncovered and the therapeutic potential of the drug in other chronic inflammatory disorders appreciated. It appears that thalidomide's therapeutic effects in ENL are due to it's ability to reduce levels of tumor necrosis factor-alpha (TNF.alpha.). (Sampaio, E. P.

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et al., Journal Of Experimental Medicine 173:699-703 (1991)). Thalidomide significantly down-regulates the production of TNF.alpha., mainly by affecting peripheral blood mononuclear cells (PBMC's), when stimulated with an appropriate agonist, e.g., microbial lipopolysaccharide (LPS). It appears to accomplish this without affecting the production of other known essential cytokines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for the treatment of cancer Inventor(s): Barer, Sol; (Westfield, NJ), Zeitlin, Andrew L.; (Basking Ridge, NJ), Zeldis, Jerome B.; (Princeton, NJ) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020035090 Date filed: May 14, 2001 Abstract: This invention relates to compositions comprising thalidomide and another anti-cancer drug which can be used in the treatment or prevention of cancer. Preferred anti-cancer drugs are topoisomerase inhibitors. A particular composition comprises thalidomide, or a pharmaceutically acceptable salt, solvate, or clathrate thereof, and irinotecan. The invention also relates to methods of treating or preventing cancer which comprise the administration of a thalidomide and another anti-cancer drug to a patient in need of such treatment or prevention. The invention further relates to methods of reducing or avoiding adverse side effects associated with the administration of chemotherapy or radiation therapy which comprise the administration of thalidomide to a patient in need of such reduction or avoidance. Excerpt(s): This invention relates to pharmaceutical compositions comprising thalidomide and an anti-cancer agent, particularly a topoisomerase inhibitor, to methods of treating cancer, and to methods of reducing or avoiding adverse effects associated with anti-cancer agents such as topoisomerase inhibitors. The incidence of cancer continues to climb as the general population ages, as new cancers develop, and as susceptible populations (e.g., people infected with AIDS) grow. A tremendous demand therefore exists for new methods and compositions that can be used to treat patients with cancer. Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, or lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). Clinical data and molecular biologic studies indicate that cancer is a multistep process that begins with minor preneoplastic changes, which may under certain conditions progress to neoplasia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cytokine antagonists for the treatment of sensorineural hearing loss Inventor(s): Tobinick, Edward L.; (Los Angeles, CA) Correspondence: Ezra Sutton, P.A.; Plaza 9; 900 Route 9; Woodbridge; NJ; 07095; US Patent Application Number: 20010004456 Date filed: December 27, 2000

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Abstract: Specific Cytokine Antagonists, including TNF antagonists and/or Interleukin1 antagonists, are used as novel therapeutic agents for the treatment of hearing loss, including presbycusis and other forms of sensorineural hearing loss. The present invention provides a method for inhibiting the action of TNF and/or IL-1 antagonists for treating hearing loss in a human by administering a TNF antagonist and/or an IL-1 antagonist for reducing the inflammation affecting the auditory apparatus of said human, or for modulating the immune response affecting the auditory apparatus of said human, by administering a therapeutically effective dosage level to said human of a TNF antagonist and/or an IL-1 antagonist. Administration may be systemic, through the subcutaneous, intramuscular, oral, or intravenous routes; or by delivering an anatomically localized application in the region of the head. The TNF antagonist is selected from the group consisting of etanercept, infliximab, D2E7, CDP 571, or thalidomide; and the IL-1 antagonist is either IL-1 RA or IL-1R type II receptor. Antiviral agents may be added for treating certain patients. Excerpt(s): This is a continuation-in-part of application Ser. No. 09/654,996, filed on Sep. 5, 2000, which is a continuation-in-part of application Ser. No. 09/563,651, filed on May 2, 2000, which is a continuation-in-part of application Ser. No. 09/476,643, filed on Dec. 31, 1999, which is a continuation-in-part of application Ser. No. 09/275,070, filed on Mar. 23, 1999, now U.S. Pat. No. 6,015,557, which is a continuation-in-part of application Ser. No. 09/256,388, filed on Feb. 24, 1999, now abandoned. The present invention is directed to specific cytokine antagonists, including TNF antagonists and IL-1 antagonists, for the treatment of hearing loss, including sensorineural hearing loss and presbycusis. The invention also includes methods of administration for these antagonists. Hearing loss occurs in humans in many forms. Hearing is essential to the normal conduct of one's daily activities and people with impaired hearing have many difficulties. Hearing loss can date from birth; it can be acquired later in life; or it can be the result of trauma, accident, disease, or a toxic effect of a medication. It can be genetic, either as a solitary disorder or as part of a complex syndrome. Hearing loss is one of the most common chronic neurological impairments, estimated to affect about 4 percent of those under 45 in the United States, and about 29 percent of those 65 years or older. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Interferon-statin combination therapy Inventor(s): Cantrell, Stephen B.; (Brentwood, TN) Correspondence: Stephen B. Cantrell, Dds, MD; 111 Mckays Court; Brentwood; TN; 37027; US Patent Application Number: 20030232033 Date filed: February 20, 2003 Abstract: A method for pharmacological treatment of cancer and other diseases is presented which includes the novel combination of a statin (Hmg-CoA reductase inhibitor, such as lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, pravastatin, or newer agents), with an interferon (such as interferon alfa-2b or others) or an angiogenesis inhibitor (a very similar and often overlapping group of drugs which inhibit blood vessel growth and maintenance, such as thalidomide, angiostatin, endostatin, or other agents), and also including concurrent administration of selenium and calcium. The method disclosed in this invention is useful because it can prove more effective than previously known therapies for certain diseases and because its use may be more tolerable, less disfiguring, and less expensive than other methods. The method

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here disclosed can be readily reproduced by any person skilled in the art of treating disease. Excerpt(s): This application claims the benefit of U.S. provisional patent application No. 60/359265 mailed Feb. 20, 2002 and received for filing Feb. 21, 2002. Not applicable. Not applicable. No drawings are pertinent to understanding, making, and using the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the treatment and/or prophylaxis of diseases caused by IL-12 Inventor(s): Frosch, Stefanie; (Aachen, DE), Germann, Tieno; (Aachen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030021763 Date filed: May 29, 2002 Abstract: A method for the treatment or prophylaxis of a disease caused by the production of IL-12, comprising administering to a subject in need thereof a compound selected from the group consisting of thalidomide,.alpha.-methyl thalidomide (EM 978), and 3-(1-oxo-1,3-dihydro-isoindol-2-- yl)-piperidine-2,6-dione (EM 12), simultaneously with an anti-inflammatory cytokine in an amount effective for inhibiting IL-12 production. Also disclosed is a method for inhibiting IL-12 production in a cell that is capable of producing IL-12. Excerpt(s): The present application is a continuation of international patent application no. PCT/EP00/11179, filed Nov. 11, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. DE 199 57 342.5, filed Nov. 29, 1999. The present invention relates to a combination therapy for the treatment of diseases caused by the formation of the pro-inflammatory cytokine IL-12. IL-12 is a heterodimeric molecule consisting of covalently bonded p35 and p40 chains. The molecule is formed by antigen presenting cells (monocytes/macrophages, dendritic cells, B lymphocytes). The formation of IL-12 by monocytes/macrophages is triggered either by various microbial products, such as lipopolysaccharide (LPS), lipopeptides, bacterial DNA, or in interaction with activated T lymphocytes (Trinchieri 1995. Ann. Rev. Immunol. 13: 251). IL-12 is of central immunoregulating importance and is responsible for the development of inflammation-promoting TH1 reactivities. The presence of a TH1 immune reaction against self antigens leads to the occurrence of serious diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of stabilizing and potentiating the action of anti-angiogenic substances Inventor(s): Das, Undurti Narasimha; (Norwood, MA) Correspondence: Rama B. Nath; Apt 1805; 4000, Parkside Center BLVD.; Farmers Branch; TX; 75244; US Patent Application Number: 20030096869 Date filed: February 27, 2002

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Abstract: A method of stabilizing and potentiating action of molecules of known antiangiogenic substances such as Angiostatin.RTM. or Endostatin.RTM. by using in coupling conjugation with cis-unsaturated fatty acids (c-UFAs) in the treatment of cell proliferative disorders uses c-UFAs chosen from linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and cis-parinaric acid in predetermined quantities. Preferably, the c-UFAs are in the form of polyunsaturated fatty acids (PUFAs). Uncontrolled or undesirable angiogenic activity promotes cell proliferative disorders and tumor growth, which can be inhibited by the selective use of PUFAs with antiangiogenic substances used selectively in conjunction with predetermined anti-cancer drugs. For a non-glioma type of cell proliferation disorder, a sodium, potassium or lithium salt of a PUFA is preferred to form an admixture with an anti-angiogenic substance. Anti-angiogenic substances envisaged in this invention include Angiostatin.RTM., Endostatin.RTM., platelet factor-4, TNP-470, thalidomide, interleukin-12 and metalloproteinase inhibitors (MMP). A preferred method of administration of the mixture to treat a tumor is intra-arterial administration into an artery which provides the main blood supply for the tumor. Excerpt(s): This application is a divisional of U.S. application Ser. No. 09/478,291 filed on Jan. 5, 2000. This invention relates to co-pending U.S. application Ser. No. 09/392,953 Filed on Sep. 9, 1999 and entitled "Method of Treatment for Cell Proliferative Disorders including Cancer", which is incorporated herein by reference. The present invention generally relates to the use of anti-angiogenic agents in the cure of cell proliferative disorders including cancer and other disorders caused by uncontrolled angiogenic activity in the body. More particularly, the invention is directed to the efficacious use of anti-angiogenic agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for the prevention and treatment of atherosclerosis, restenosis and related disorders Inventor(s): Zeldis, Jerome B.; (Princeton, NJ) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20020054899 Date filed: December 11, 2000 Abstract: Methods and compositions for the prevention and treatment of all forms of atherosclerosis are described. Administration of compounds such as thalidomide, its analogs, hydrolysis products, metabolites, derivatives and precursors as well as additional compounds capable of inhibiting tumor necrosis factor.alpha. (TNF-.alpha.) are used in the invention.Also disclosed is the coating of prosthetic devices, such as stents, with the compounds of the invention for the prevention and/or treatment of restenosis. Excerpt(s): The invention is directed to methods and compositions for the prevention and treatment of all forms of atherosclerosis, including atherosclerosis found in the cardiovascular and renal systems. More particularly, the present invention relates to the prevention and or reduction of stenosis and restenosis by administration of compounds such as thalidomide, its analogs, hydrolysis products, metabolites, derivatives and precursors of thalidomide. Compounds which may be used in the methods and

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compositions of the invention typically are capable of inhibiting tumor necrosis factor.alpha. (TNF-.alpha.). In another embodiment, the present invention is directed to the coating of prosthetic devices with these compounds for use or implantation into a subject, preferably a human. Preferred prosthetic devices include, for example, stents coated with the compounds for the prevention and/or treatment of restenosis. In 1994, there were almost 1 million deaths due to vascular disease in the United States (twice as many as from cancer and 10 times as many as from accidents). Vascular disease may affect the brain, heart, kidneys, other vital organs as well as the extremities. The most common and serious vascular disease is atherosclerosis. Atherosclerosis is characterized by patchy subintimal thickening (atheromas) of the medium-sized arteries such as the coronary arteries, mesenteric arteries, renal arteries and carotid arteries and the large arteries such as the aorta. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for the inhibition of angiogenesis with 6-amino EM-12 Inventor(s): D'Amato, Robert; (Lancaster, PA) Correspondence: Jennifer R. Seng; Kilpatrick Stockton Llp; Suite 2800; 1100 Peachtree Street; Atlanta; GA; 30309; US Patent Application Number: 20010056113 Date filed: July 5, 2001 Abstract: The present invention comprises a group of compounds that effectively inhibit angiogenesis. More specifically, thalidomide and various related compounds such as thalidomide precursors, analogs, metabolites and hydrolysis products have been shown to inhibit angiogenesis and to treat disease states resulting from angiogenesis. Importantly, these compounds can be administered orally. Excerpt(s): This application is a divisional of Application Ser. No. 08/950,673, filed Oct. 16, 1997, which is a continuation-in-part of U.S. patent application Ser. No. 08/025,046, filed Mar. 1, 1993. The present invention relates to methods and compositions for preventing unwanted angiogenesis in a human or animal. More particularly, the present invention relates to a method for preventing unwanted angiogenesis, particularly, in angiogenesis dependent or associated diseases, by administration of compounds such as thalidomide and related compounds. As used herein, the term "angiogenesis" means the generation of new blood vessels into a tissue or organ. Under normal physiological conditions, humans or animals only undergo angiogenesis in very specific restricted situations. For example, angiogenesis is normally observed in wound healing, fetal and embryonal development and formation of the corpus luteum, endometrium and placenta. The control of angiogenesis is a highly regulated system of angiogenic stimulators and inhibitors. The control of angiogenesis has been found to be altered in certain disease states and, in many cases, the pathological damage associated with the disease is related to the uncontrolled angiogenesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of using a combination of cyclooxygenase-2 selective inhibitors and thalidomide for the treatment of neoplasia Inventor(s): Masferrer, Jaime L.; (Ballwin, MO) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20030013739 Date filed: April 30, 2002 Abstract: The present invention provides compositions and methods for the treatment, prevention or inhibition of neoplasia by administering an effective amount of a cyclooxygenase-2 selective inhibitor in combination with an effective amount of thalidomide. Excerpt(s): This application is a continuation-in-part application of PCT/US99/30693, filed Dec. 22, 1999, which claims priority from U.S. provisional patent application no. 60/113,786, filed Dec. 23, 1998, both of which are incorporated herein by reference. The present invention is directed to compositions comprising a cyclooxygenase-2 inhibitor or a pharmaceutically acceptable salt, ester or prodrug thereof and a thalidomide, thalidomide analog, thalidomide hydrolysis product, thalidomide metabolite or thalidomide precursor, wherein said compositions are useful for the treatment, prevention or inhibition of neoplasia disorder. Further provided are methods for treatment, prevention or inhibition of neoplasia disorders utilizing said compositions. Cancer is now the second leading cause of death in the United States where over 8,000,000 persons have been diagnosed with some form of cancer. In 1995, cancer accounted for 23.3% of all deaths in the United States. (See U.S. Dept. of Health and Human Services, National Center for Health Statistics, Health United States 1996-97 and Injury Chartbook 117 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical composition for the treatment of hepatocellular carcinoma Inventor(s): Chang, Jang-Yang; (Taipei, TW), Chen, Li-Tzong; (Kaohsiung City, TW), Hsu, Ming-Chu; (Taipei, TW), Huang, Chun-Ying; (Taipei, TW), Liu, Tsang-Wu; (Taipei, TW), Whang-Peng, Jia-Kang; (Taipei, TW) Correspondence: Ladas & Parry; 26 West 61st Street; New York; NY; 10023; US Patent Application Number: 20010018445 Date filed: January 24, 2001 Abstract: The invention mainly discloses a pharmaceutical composition for use in the treatment of hepatocellular carcinoma, which comprises thalidomide and a pharmaceutically acceptable carrier. Excerpt(s): Thalidomide was first synthesized in 1953, and it was widely used as a sedative and for the prevention of vomiting during pregnancy. In 1963, it was found that women who took thalidomide in the first trimester of pregnancy would deliver terata, such as phocomelia. Therefore, thalidomide was prohibited in Europe and the USA. In view of studies in recent years, thalidomide has the efficacy on adjustment of the immune system which may treat immune system related diseases. For instance, Arch Dermatol. 1993, vol. 129, p. 1548-1550 described the use of thalidomide in the treatment of cutaneous lupus erythematosus; the Journal of Rheumatology, 1989, 16, p.

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159-163 described the use of thalidomide in the treatment of refractory rheumatoid arthritis; Arch Dermatol. 1990, vol. 126, p. 923-927 described the use of thalidomide in the treatment of Behcet's syndrome; Journal of Pediatr. Gastroenerol. Nurt. 1999, vol. 28, p. 214-216 described the use of thalidomide in the treatment of Cornh's disease; and Journal of Rheumatology, 1998, vol. 25, p.964-969 described the use of thalidomide in the treatment of rheumatoid arthritis. In addition, U.S. Pat. Nos. 5,593,990 and 5,629,327 disclose that thalidomide could effectively inhibit angiogenesis; U.S. Pat. No. 5,654,312 discloses the methods of treatment for inflammatory and autoimmune dermatoses. In addition, the Journal of Infectious Diseases, 1993, 168, p. 408-414 taught that thalidomide could effectively inhibit tumor necrotic factor-alpha (TNF-I). Anti-Cancer Drugs, 1996, 7, p.339-343 demonstrated that thalidomide could effectively inhibit basic fibroblast growth factor-induced angiogenesis. Thalidomide is widely applied in the clinical treatment of malignant tumors which are highly vascular and cannot be effectively treated by chemical therapy. For instance, U.S. Pat. No. 5,696,092 discloses the use of thalidomide in the inhibition of metastases of cancers of epithelial cell origin, especially human prostate cancers. Among the above prior art references, none of the references or patents teaches that thalidomide could be specifically used in the treatment of hepatocellular carcinoma. Up to the present time, there are not any drugs that can effectively treat hepatocellular carcinoma. Patients with metastatic hepatocellular carcinoma or hepatocellular carcinoma, where local treatment has failed, normally survive for only three to four months. Metastatic hepatocellular carcinoma or hepatocellular carcinoma, where local treatment has failed, is mainly subjected to systemic therapy. The use of Doxorubicin, a high dosage of Tamoxifen in combination Doxorubicin or EA-PFL (etopoxide, adrimycin, cisplatin, fluorouracil and leucovorin), is an effective example. The remission rate of those drugs can achieve levels between 15 and 30%. However, because the patients of hepatocellular carcinoma usually develop complication of liver cirrhosis and other complications (such as leukopenia, thrombopenia or liver function impairment), they cannot be subject to systemic chemotherapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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

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

Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine by Trent D. Stephens, Rock Brynner; ISBN: 0738205907; http://www.amazon.com/exec/obidos/ASIN/0738205907/icongroupinterna

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Thalidomide : "Y" list inquiry : report by Alan Marre; ISBN: 0113202482; http://www.amazon.com/exec/obidos/ASIN/0113202482/icongroupinterna

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Thalidomide : important patient information (SuDoc HE 20.4002:T 32/996) by U.S. Dept of Health and Human Services; ISBN: B00010U72K; http://www.amazon.com/exec/obidos/ASIN/B00010U72K/icongroupinterna

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Thalidomide : my fight by David Mason; ISBN: 0049200461; http://www.amazon.com/exec/obidos/ASIN/0049200461/icongroupinterna

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Thalidomide : potential benefits and risks : January 1963 through July 1997 : 1495 citations (SuDoc HE 20.3615/2:97-4) by Karen Patrias; ISBN: B00010UMKW; http://www.amazon.com/exec/obidos/ASIN/B00010UMKW/icongroupinterna

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Thalidomide : the legal aftermath by Harvey Teff; ISBN: 0566001209; http://www.amazon.com/exec/obidos/ASIN/0566001209/icongroupinterna

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Thalidomide and the power of the drug companies by Henning Sjöström; ISBN: 0140522980; http://www.amazon.com/exec/obidos/ASIN/0140522980/icongroupinterna

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Thalidomide: Index of New Information for Research, Reference & Therapy by Max C. Dobber; ISBN: 0788318780; http://www.amazon.com/exec/obidos/ASIN/0788318780/icongroupinterna

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The challenge of Thalidomide: a pilot study of the educational needs of children in Scotland affected by the drug by M. L. Kellmer Pringle; ISBN: 0582324483; http://www.amazon.com/exec/obidos/ASIN/0582324483/icongroupinterna

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The great drug deception; the shocking story of MER/29 and the folks who gave you thalidomide by Ralph Adam Fine; ISBN: 0812814703; http://www.amazon.com/exec/obidos/ASIN/0812814703/icongroupinterna

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The Sunday times thalidomide case : contempt of court and the freedom of the press by Murray Rosen; ISBN: 0904286185; http://www.amazon.com/exec/obidos/ASIN/0904286185/icongroupinterna

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The Thalidomide children and the law : a report; ISBN: 0233965386; http://www.amazon.com/exec/obidos/ASIN/0233965386/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “thalidomide” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •

Great drug deception; the shocking story of MER 29 and the folks who gave you thalidomide. Author: Fine, Ralph Adam, 1941-; Year: 1972

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Suffer the children: the story of thalidomide. Author: the Insight team of the Sunday Times of London, Phillip Knightley. [et al.]; Year: 1979

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Thalidomide: the legal aftermath. Author: Harvey Teff, Colin R. Munro; Year: 1976

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Thalidomide disaster and its impact on modern medicine. Author: by P. I. Folb; Year: 1977

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Thalidomide embryopathy in Japan. Author: edited by Mitsushiro Kida; Year: 1987

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

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

Disability, the Young and the Elderly Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 470-487. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Disability is caused by handicapping conditions that impair normal social, educational, or recreational activities. Such patients need dental attention and treatment to at least the same standard as non-handicapped patients; frequently this population has a greater predisposition to dental disease. This chapter on disability, the young and the elderly is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. This chapter covers only patients with mental and related handicaps, some specific conditions, children, and the elderly; patients with other important specific diseases, such as hemophilia, neurological disorders and muscular dystrophies, are covered in other chapters. Topics include learning disability, chromosomal anomalies (including Down syndrome and fragile X syndrome), thalidomide defect, hydrocephalus, cleft lip and palate, autism, the overactive child (hyperkinetic child), child abuse, self-inflicted oral lesions, juvenile delinquency, and problems in the elderly, including multiple disease, intellectual failure, social problems, drug compliance and reactions. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 5 figures. 8 tables. 46 references.

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Inflammatory Bowel Disease and Pregnancy Source: in Satsangi, J.; Sutherland, L.R., eds. Inflammatory Bowel Diseases. St. Louis, MO: Elsevier Science. 2003. p. 717-727. Contact: Available from Elsevier Science. Customer Service Department, 11830 Westline Industrial Drive, St. Louis, MO 63146 (800) 545-2522. Fax (800) 535-9935. Email: [email protected]. Website: www.elsevierhealth.com. PRICE: $149.00. ISBN: 443071217. Summary: Inflammatory bowel disease (IBD) is a chronic and relatively common disorder of uncertain etiology (cause). This chapter on IBD and pregnancy is from a comprehensive textbook that serves as a reference for scientists, physicians, and surgeons involved in all aspects of Crohn's disease and ulcerative colitis (IBD). In this chapter, the author reviews the knowledge of the effects of IBD on fertility treatments, the fate of pregnancy (preterm birth, malformations), and the risk of transmission of the

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disease to the offspring. The author also summarizes information from the literature which helps in the management of IBD in pregnant women, lactating women, and adults who desire to have children. The author notes that women with IBD have an increased risk of preterm delivery. The risk of ongoing disease activity during pregnancy is higher in women who become pregnant during an active phase of the disease. The use of drugs to treat IBD in pregnant women or in adults who desire to have children must be cautious and take into account both the changes of efficacy against the disease and the risks for the fetus. Methotrexate, quinolones, and thalidomide are definitely contraindicated. 2 figures. 2 tables. 90 references. •

Old and New Immunosuppressant Drugs: Mechanisms and Potential Value Source: in Lindor, K.D.; Heathcote, E.J.; Poupon, R., eds. Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment. Boston, MA: Kluwer Academic Publishers. 1998. p. 115-123. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: Primary biliary cirrhosis (PBC) is a chronic cholestasic (lack of bile flow) liver disease of unknown etiology (cause), although the association with a large number of autoimmune disorders suggests that the disease may be of autoimmune origin. The disease usually affects middle aged women and progresses from asymptomatic disease with only laboratory abnormalities to a severe cholestatic disease with deep jaundice, xanthomas (fatty tumors in the skin), portal hypertension (high blood pressure), and eventually liver failure. This chapter on the use of immunosuppressant agents to treat PBC is from a monograph that reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of PBC. The goals of immunosuppression in PBC are to prevent or retard immunologic mechanisms of non suppurative destructive cholangitis (inflammation of the bile ducts), periportal hepatitis (liver inflammation)and cytokine induced portal fibrosis (scarring) while minimizing morbidity (complications) and mortality (death) associated with immunosuppression. The author reviews the mechanisms of action and potential of different immunosuppressive agents, including corticosteroids, azathioprine, cyclosporine, tacrolimus (FK506), mycophenolate mofetil, methotrexate, ursodeoxycholic acid (UDCA), and thalidomide. The author also considers experimental or investigational immunosuppressive agents, including sirolimus (rapamycin), mizoribine, and gusperimus (deoxyspergualin). The author concludes that it must be resolved whether PBC is an infectious or autoimmune disease before definitive treatment can be established. If immunosuppression is found to be useful in PBC, it will likely be administered as combination therapy and will be tailored to the stage of disease. 2 figures. 2 tables. 24 references.

•

Anticytokine Therapy in Crohn's Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 389-393. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220.

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Summary: This chapter on the use of anticytokine therapy in treating Crohn's disease (CD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with CD and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Research into the immunopathogenetic processes of IBD has resulted in the identification of a variety of inflammatory mediators, including cytokines, which are elevated in the mucosa of patients with CD. The current trend in treatment development is the manipulation of these mediators to render antiinflammatory effects more specific than are provided by the traditional therapeutic options. Recent developments have centered on selective inhibition of expression or activity of these mediators of inflammation. Most progress has been made in the compounds that downregulate or completely inhibit the effect of tumor necrosis factor-alpha (TNF-a ). Remicade (Centocor Inc., Malvern, Pennsylvania) and Enbrel (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania), both of which recently received FDA approval for use in CD and juvenile rheumatoid arthritis, respectively, are anti-TNFa preparations with different mechanisms of action. Another promising agent with potent anti-TNF properties is thalidomide. It is recommended that these agents, however effective, not be used as first-line therapy. This chapter provides guidelines for the use of anticytokine therapy for patients with CD and summarizes the clinical experience to date with TNF blockade. 1 table. 10 references. •

Chapter 22: Behcet's Disease Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 415-418. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This chapter provides health professionals with information on the pathogenesis, clinical features, diagnosis, and treatment of Behcet's disease (BD). This chronic inflammatory vascular disorder of unknown etiology occurs mainly in young adults. The prevalence is highest in countries of the eastern Mediterranean, the Middle East, and East Asia. Although genetic studies have demonstrated a strong association with human leukocyte antigen B51, the role of this gene in the development of BD is uncertain. Another candidate is the MICA gene. Aphthous oral ulcers are the most common feature of BD. Genital ulcers may also occur. Various types of skin lesions are common as well. A positive pathergy test is highly specific for BD. Ocular inflammation usually follows mucocutaneous symptoms by a few years. Other systems affected by BD include large vessels of both the arterial and venous systems, the central nervous system, and the gastrointestinal system. Many patients with BD are affected by an intermittent, symmetric oligoarthritis of the knees, ankles, hands, or wrists. Diagnosis is based on clinical judgment and the presence of recurrent oral ulceration, plus two of the following: recurrent genital ulceration, eye lesions, skin lesions, and a positive pathergy test. Topical or intralesional corticosteroids or dapsone is used to treat aphthous lesions. Drugs used to treat other manifestations include colchicine, thalidomide, methotrexate, azathioprine, and cyclosporine. Surgery is usually needed to treat systemic arterial aneurysms that are at risk for rupture. 3 figures, 1 table, and 21 references.

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

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

Thalidomide helpful in refractory ankylosing spondylitis Source: Reuters Medical News Date: January 12, 2004

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Thalidomide with carmustine active against brain tumors Source: Reuters Industry Breifing Date: July 15, 2003

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Thalidomide may carry dementia risks: case report Source: Reuters Health eLine Date: May 01, 2003

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Celgene beats Q1 expectations on strong Thalomid sales Source: Reuters Industry Breifing Date: April 24, 2003

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Thalidomide may slow some prostate cancers: study Source: Reuters Health eLine Date: March 27, 2003

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Thalidomide may slow progression of androgen-independent prostate cancer Source: Reuters Industry Breifing Date: March 27, 2003

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Thalidomide may be useful for complex regional pain syndrome type 1 Source: Reuters Industry Breifing Date: March 21, 2003

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Thalidomide-like drug has potential to fight cancer Source: Reuters Health eLine Date: February 03, 2003

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Thalidomide analogue shows direct anti-tumour activity in vitro Source: Reuters Industry Breifing Date: February 03, 2003

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New thalidomide trial goes ahead in lung cancer Source: Reuters Health eLine Date: January 28, 2003

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Large new thalidomide trial goes ahead in lung cancer Source: Reuters Industry Breifing Date: January 27, 2003

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Europe discusses safe re-launch of thalidomide Source: Reuters Health eLine Date: January 20, 2003

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Companies, patients discuss EU re-launch of thalidomide Source: Reuters Industry Breifing Date: January 20, 2003

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Thalidomide effective for previously untreated multiple myeloma Source: Reuters Industry Breifing Date: January 17, 2003

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Thalidomide confirmed to have survival benefit in multiple myeloma Source: Reuters Industry Breifing Date: January 15, 2003

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Thalidomide slows blood cancer Source: Reuters Health eLine Date: January 14, 2003

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EntreMed licenses thalidomide programmes to Celgene Source: Reuters Industry Breifing Date: January 02, 2003

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Thalidomide associated with thromboembolic events Source: Reuters Medical News Date: December 26, 2002

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Thalidomide improves cardiac function in chronic heart failure Source: Reuters Medical News Date: December 06, 2002

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Thalidomide/steroid therapy effective for newly diagnosed multiple myeloma Source: Reuters Medical News Date: November 06, 2002

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Thalidomide combo fights bone marrow cancer-study Source: Reuters Health eLine Date: October 31, 2002

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Thalidomide-like drugs have anti-cancer properties Source: Reuters Health eLine Date: October 30, 2002

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Deep vein thrombosis risk high in myeloma patients treated with doxorubicin and thalidomide Source: Reuters Medical News Date: September 06, 2002

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Chronic cutaneous sarcoidosis seems to respond to thalidomide therapy Source: Reuters Medical News Date: July 29, 2002

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Thalidomide may be effective for treatment-resistant ankylosing spondylitis Source: Reuters Medical News Date: July 05, 2002

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Temozolomide plus thalidomide well tolerated in melanoma patients Source: Reuters Medical News Date: June 14, 2002

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Thalidomide well tolerated in HIV-infected patients Source: Reuters Medical News Date: May 24, 2002

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Renal cell cancer may adapt to inhibitory effects of thalidomide Source: Reuters Medical News Date: May 08, 2002

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Thalidomide benefits some in leukemia study Source: Reuters Health eLine Date: February 18, 2002

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Celgene Q4 profits rise on Thalomid sales, milestone payment Source: Reuters Industry Breifing Date: January 30, 2002

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Celgene's Thalomid wins EU orphan status Source: Reuters Medical News Date: December 21, 2001

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Thalidomide may relieve rare pain disorder: report Source: Reuters Health eLine Date: November 16, 2001

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Thalidomide sends melanoma patient into remission Source: Reuters Health eLine Date: October 17, 2001

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New Thalomid label warns of seizure risk Source: Reuters Medical News Date: September 11, 2001

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Thalidomide regimen for multiple myeloma linked to increased DVT risk Source: Reuters Industry Breifing Date: August 28, 2001

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Thalidomide active against Waldenström's macroglobulinemia Source: Reuters Industry Breifing Date: August 24, 2001

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Thalidomide shows promise in treating myelodysplastic syndrome Source: Reuters Medical News Date: August 09, 2001

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Thalidomide shows promise in another blood cancer Source: Reuters Health eLine Date: August 08, 2001

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EntreMed sells thalidomide royalty stream for $24.3 million Source: Reuters Industry Breifing Date: August 08, 2001

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Thalidomide may treat early-stage blood cancer Source: Reuters Health eLine Date: August 07, 2001

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Thalidomide effective for early-stage multiple myeloma Source: Reuters Industry Breifing Date: July 27, 2001

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Response of refractory multiple myeloma to thalidomide spans 2 years Source: Reuters Industry Breifing Date: July 12, 2001

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Celgene, Roche start phase II studies of Thalomid/Xeloda as anticancer combo Source: Reuters Industry Breifing Date: June 01, 2001

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Pharmacia, Celgene to test whether Thalomid improves colorectal cancer drug regimen Source: Reuters Industry Breifing Date: May 17, 2001

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Thalomid elicits high response in phase II multiple myeloma studies Source: Reuters Industry Breifing Date: May 15, 2001

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Mixed results for Celgene's Thalomid in renal cell cancer studies Source: Reuters Industry Breifing Date: May 14, 2001

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Thalomid shows most promise in combined therapy for multiple myeloma Source: Reuters Industry Breifing Date: May 11, 2001

Periodicals and News

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Thalidomide better for multiple myeloma if combined with other drugs Source: Reuters Medical News Date: May 11, 2001

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Celgene reports slow Q1 sales growth for Thalomid Source: Reuters Industry Breifing Date: April 27, 2001

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Thalidomide does not prevent recurrence of HIV-associated aphthous ulcers Source: Reuters Industry Breifing Date: February 16, 2001

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. 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 “thalidomide” (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 “thalidomide” (or synonyms). If you know the name of a company that is relevant to thalidomide, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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

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

Update on Management of Scleroderma Source: Bulletin on the Rheumatic Diseases. 49(10): 1-4. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on the management of scleroderma. This chronic disease targets the skin, heart, lungs, gastrointestinal tract, kidneys, muscles, and joints. Scleroderma is classified into limited and diffuse cutaneous forms. Almost all patients with scleroderma have Raynaud's phenomenon (RP). The most effective way to prevent RP is to avoid exposure to cold. Calcium channel blockers are currently the most effective and safest vasodilators for scleroderma related RP. Other useful medications include coated aspirin and intravenous prostaglandins. Options for managing gastrointestinal disease include elevating the head of the bed, using antacids, making dietary changes, and taking oral motility agents. Prostaglandins and their analogs are now available to treat pulmonary hypertension. Immunosuppressive agents can be useful in treating interstitial lung disease. Renal disease can be treated with angiotensin converting enzyme inhibitors. Disease modifying agents that can be used to treat early diffuse scleroderma include colchicine, paraaminobenzoic acid, and D-penicillamine. Other drugs that have been investigated for treating early diffuse scleroderma include relaxin, halofuginone, glucocorticoids, methotrexate, thalidomide, and cyclophosphamide. People who have scleroderma are more likely to experience major depression, so good pain control and the use of antidepressants are important. 1 table and 12 references.

Academic Periodicals covering Thalidomide Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to thalidomide. In addition to these sources, you can search for articles covering thalidomide that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to

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http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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

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

Systemic - U.S. Brands: THALOMID http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202692.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 Institute11: •

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

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

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

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

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

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

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

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

11

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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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/

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

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

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

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

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

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

•

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

12

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

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “thalidomide” (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 5098 78 850 47 15 6088

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

14

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

15

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

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

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

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

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

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

•

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

The Genome Project and Thalidomide In the following section, we will discuss databases and references which relate to the Genome Project and thalidomide. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “thalidomide” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for thalidomide: •

Thalidomide Susceptibility Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=273600 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

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

•

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

•

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

•

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

•

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

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•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “thalidomide” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “thalidomide” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

23

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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

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Behcet's Syndrome http://www.nlm.nih.gov/medlineplus/behcetssyndrome.html Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Bone Marrow Diseases http://www.nlm.nih.gov/medlineplus/bonemarrowdiseases.html Multiple Myeloma http://www.nlm.nih.gov/medlineplus/multiplemyeloma.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 thalidomide. 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: •

Behcet's Disease Source: Detroit, MI: American Autoimmune Related Diseases Association, Inc. 1998. 2 p. Contact: Available from American Autoimmune Related Diseases Association, Inc. (AARDA). Michigan National Bank Building, 15475 Gratiot Avenue, Detroit, MI 48205. (313) 371-8600. Website: www.aarda.org. PRICE: Single copy free; send self-addressed, stamped envelope. Summary: This fact sheet for people with Behcet's disease discusses the affected population, symptoms, and treatment of this rare, chronic, multisystem autoimmune disease that involves inflammation of blood vessels throughout the body. Onset is usually between the ages of 20 and 30. The disease affects twice as many men as women, and it is most common in Eastern Mediterranean countries and in eastern Asia. Symptoms include recurrent mouth and genital ulcers, eye and skin lesions, fatigue, and fever. Arthritis is frequently present, and bowel inflammation can occur as well. Treatment is symptom specific and may include topical corticosteroids, thalidomide, and nonsteroidal anti-inflammatory, antigout, and immunosuppressive drugs. The fact sheet also explains what autoimmunity is, lists other common autoimmune diseases, and outlines the activities of the American Autoimmune Related Diseases Association. 3 references.

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•

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Weight Loss and Wasting Syndrome 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, written for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), provides information about weight loss and wasting syndrome. Symptoms of wasting system include unexplained involuntary weight loss, fever, and/or diarrhea. The fact sheet describes the chemical functions that take place in the body to convert food to lean body mass and fat and the process by which the body begins to lose weight and break down lean body mass. Reasons for this latter process in HIV-positive people are not fully understood by doctors. Some of the factors that may contribute to weight loss and wasting syndrome include the development of a new illness, medication side effects, weakness that prohibits individuals from feeding themselves, depression, nausea/vomiting, mouth pain, difficulty swallowing, and long-term diarrhea. Some of the ways by which weight loss can be managed medically are identified. These methods include treatments with antiretrovirals, megestrol acetate (Megace), dronabinol (Marinol), testosterone, growth hormones, thalidomide, and hyperalimentation. The benefits and possible side effects of these drugs are discusses. A table identifies the factors contributing to weight loss in HIV, their causes, and the ways by which they are managed. Healthfinder™

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

FAQ - About Thalidomide Summary: This document answers consumers' most frequently asked questions received by the Center for Drug Evaluation and Research concerning the drug Thalidomide. Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3641

•

Thalidomide Information for Consumers Summary: This document provides details about the drug thalidomide including manufacturer, active ingredient, dosage, approved usage and side effects. Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3640 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 thalidomide. The drawbacks of this approach are that the information is not

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organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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Simply type in “thalidomide” (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 “thalidomide”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “thalidomide” (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 “thalidomide” (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.25

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

25

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)26: •

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

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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

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

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

•

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

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

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

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

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

•

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

26

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

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•

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

•

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

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

•

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

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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/

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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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

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

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

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

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THALIDOMIDE 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] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [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] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH]

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Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] 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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU]

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Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Alopecia: Absence of hair from areas where it is normally present. [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] Alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins. [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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] 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]

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Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [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] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] 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] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anomalies: Birth defects; abnormalities. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by

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contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antiangiogenesis: Prevention of the growth of new blood vessels. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] 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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidote: A remedy for counteracting a poison. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress 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] 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]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antitumour: Counteracting tumour formation. [EU]

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Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aphthous Stomatitis: Inflammation of the mucous membrane of the mouth. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arsenic trioxide: An anticancer drug that induces programmed cell death (apoptosis) in certain cancer cells. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthus Reaction: A dermal inflammatory reaction produced under conditions of antibody excess, when a second injection of antigen produces intravascular antigen-antibody complexes which bind complement, causing cell clumping, endothelial damage, and vascular necrosis. [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] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells

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called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as

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sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH]

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Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluid Compartments: The two phases between which water and other body fluids are distributed: extracellular and intracellular. [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

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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] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiolitis Obliterans: Inflammation of the bronchioles with obstruction by fibrous granulation tissue or bronchial exudate. It may follow inhalation of irritating gases or foreign bodies and it complicates pneumonia. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal

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functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [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] 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] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] 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] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]

Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH]

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Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [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] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Hypoxia: A condition of decreased oxygen content at the cellular level. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [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] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that

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develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

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] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] 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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]

Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Choleretic: A choleretic agent. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a

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characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatricial: Ectropion due to scar tissue on the margins or the surrounding surfaces of the eyelids. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cicatrix, Hypertrophic: An elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] 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] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other

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medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] 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] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols

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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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] 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] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual

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process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [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] Constriction: The act of constricting. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called

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also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] 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] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] 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]

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Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [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] Cytokinin: One of a group of N-substituted adenines which promote the division of plant cells. [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]

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Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Deception: The act of deceiving or the fact or condition of being deceived. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Deoxycytidine: A drug that protects healthy tissues from the toxic effects of anticancer drugs. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] 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] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in

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common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diethylstilbestrol: DES. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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 tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] 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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discoid: Shaped like a disk. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [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 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] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

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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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Dronabinol: A synthetic pill form of delta-9-tetrahydrocannabinol (THC), an active ingredient in marijuana that is used to treat nausea and vomiting associated with cancer chemotherapy. [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] Duct: A tube through which body fluids pass. [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] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [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

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based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] 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]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryotoxicity: Any toxic effect on the conceptus as a result of prenatal exposure during the embryonic stages of development. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have

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filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple,

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and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Ulcer: A sore in the esophagus. Caused by long-term inflammation or damage from the residue of pills. The ulcer may cause chest pain. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxins: Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] 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] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of

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protein, cells, or solid materials derived from cells. [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] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH]

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Flexor: Muscles which flex a joint. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] 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] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungicide: An agent that destroys fungi. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH]

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Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geographic Locations: All of the continents and every country situated within, the United States and each of the constituent states arranged by region, Canada and each of its provinces, Australia and each of its states, the major bodies of water and major islands on both hemispheres, and selected major cities. Although the geographic locations are not printed in index medicus as main headings, in indexing they are significant in epidemiologic studies and historical articles and for locating administrative units in education and the delivery of health care. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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]

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Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem

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cells against a person's tissue. [NIH] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Gynecologic oncologist: A doctor who specializes in treating cancers of the female reproductive organs. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH]

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Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hexachlorobenzene: An agricultural fungicide and seed treatment agent. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Agonists: Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically. [NIH] Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH]

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Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [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] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount

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of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperkalaemia: Pathology: an abnormally high concentration of potassium in the blood. [EU]

Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] 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] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Idiopathic myelofibrosis: A progressive disease in which the bone marrow is replaced by fibrous tissue and is unable to produce red blood cells; the cause is unknown. [NIH] Idiotype: The unique antigenic determinant in the variable region. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They

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are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [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] Immunologic Diseases: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated or both. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [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] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH]

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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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or

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silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [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 Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [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-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH]

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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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Ipsilateral: Having to do with the same side of the body. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Juvenile Delinquency: The antisocial acts of children or persons under age which are illegal or lawfully interpreted as constituting delinquency. [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] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH]

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Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] LDL: 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] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [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] Leukocyte Count: A count of the number of white blood cells per unit volume in venous blood. A differential leukocyte count measures the relative numbers of the different types of white cells. [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense

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reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Lindane: An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] 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]

Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH]

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Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lye: Generally speaking, it is the alkaline substance obtained from wood ashes by percolation. Preparations of lye can either be solutions of potassium or sodium hydroxide. The term lye, is also used to refer to the household product which is a mixture of sodium hydroxide and sodium carbonate. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte 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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [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] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH]

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Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macroglia: A type of neuroglia composed of astrocytes. [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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Maternal-Fetal Exchange: Exchange of substances between the maternal blood and the fetal blood through the placental barrier. It excludes microbial or viral transmission. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical oncologist: A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, and biological therapy. A medical oncologist often serves as the main caretaker of someone who has cancer and coordinates treatment provided by other specialists. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [NIH]

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Megestrol Acetate: A drug that belongs to the group of hormones called progestins, used as hormone therapy to block estrogen and to suppress the effects of estrogen and androgens. [NIH]

Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH]

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Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] 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] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH]

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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] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] 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] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH]

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Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]

Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [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] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH]

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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] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neurofibroma: A fibrous tumor, usually benign, arising from the nerve sheath or the endoneurium. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuroma: A tumor that arises in nerve cells. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH]

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Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH]

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Orchitis: Inflammation of a testis. The disease is marked by pain, swelling, and a feeling of weight. It may occur idiopathically, or it may be associated with conditions such as mumps, gonorrhoea, filarial disease, syphilis, or tuberculosis. [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [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]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [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]

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Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Paradoxical: Occurring at variance with the normal rule. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Participation: Patient involvement in the decision-making process in matters pertaining to health. [NIH] Pelvic: Pertaining to the pelvis. [EU]

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Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Pericytes: Smooth muscle cell that wraps around normal blood vessels. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH]

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Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [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] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phocomelia: Congenital deformity that leaves the child without legs. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] 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]

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Plant Oils: Oils derived from plants or plant products. [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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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]

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Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or

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symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presbycusis: Progressive bilateral loss of hearing that occurs in the aged. Syn: senile deafness. [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] Primary tumor: The original tumor. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proliferative Retinopathy: A disease of the small blood vessels of the retina of the eye. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propionic Acids: 3-carbon saturated monocarboxylic acids. [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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to

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indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] 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] Protons: Stable elementary particles having the smallest known positive charge, found in the

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nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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 Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a

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thin fluid called liquor puris). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring systems. [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 oncologist: A doctor who specializes in using radiation to treat cancer. [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 in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] 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] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and

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causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [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 cell cancer: Cancer that develops in the lining of the renal tubules, which filter the blood and produce urine. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU]

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Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Salivary: The duct that convey saliva to the mouth. [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.

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Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scabicide: An agent which has the power to destroy sarcoptes scabiei. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH]

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Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Sickness: Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by

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a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Single-agent: The use of a single drug or other therapy. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Somnolence: Sleepiness; also unnatural drowsiness. [EU]

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Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [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 Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH]

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Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors

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contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] 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] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] 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] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

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Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [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] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [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] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include

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cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [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

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toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachoma: A chronic infection of the conjunctiva and cornea caused by Chlamydia trachomatis. [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] 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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichloroacetic Acid: A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other

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mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Unresectable: Unable to be surgically removed. [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] 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] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH]

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Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Ventricular: Pertaining to a ventricle. [EU] 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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [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] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some

Dictionary 225

viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitelline Membrane: The plasma membrane of the egg. [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] Volition: Voluntary activity without external compulsion. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xenopus: An aquatic genus of the family Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes. [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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [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] Zygote: The fertilized ovum. [NIH]

227

INDEX A Abdominal, 100, 155, 196, 203, 204, 223 Abdominal Pain, 155, 223 Aberrant, 15, 155 Acceptor, 155, 193, 202 Acetic Acids, 98, 155 Acetylcholine, 155, 168, 200 Acne, 155, 213 Acoustic, 106, 155 Actin, 155, 199 Acute myelogenous leukemia, 28, 34, 155 Acute myeloid leukemia, 29, 155 Acute nonlymphocytic leukemia, 155 Adaptability, 155, 166 Adaptation, 10, 155 Adenocarcinoma, 15, 45, 155, 185 Adhesions, 100, 155 Adipose Tissue, 156, 203 Adjustment, 112, 155, 156 Adjuvant, 19, 27, 38, 156 Adjuvant Therapy, 38, 156 Adrenal Glands, 156, 157 Adverse Effect, 4, 5, 107, 156, 215 Affinity, 26, 156, 160, 216 Agonist, 107, 156, 176 Albumin, 156, 206 Algorithms, 156, 163 Alimentary, 34, 63, 156, 203 Alkaline, 156, 164, 194 Alkaloid, 156, 165, 169, 211 Alkylating Agents, 25, 156, 165, 220 Allergen, 102, 156, 174, 215 Allogeneic, 46, 157, 183 Allogeneic bone marrow transplantation, 46, 157 Alopecia, 157, 173 Alpha Particles, 157, 211 Alpha-1, 157, 173 Alpha-Linolenic Acid, 110, 157 Alternative medicine, 125, 157 Ameliorating, 102, 104, 157 Amine, 157, 185 Amino Acids, 14, 157, 165, 204, 207, 209 Amyloid, 22, 157 Amyloidosis, 22, 157 Anabolic, 6, 157, 175 Anaesthesia, 157, 189 Analgesic, 157, 175, 193, 201, 211

Analog, 21, 33, 101, 105, 112, 158, 181, 197 Analogous, 96, 158, 222 Analytes, 9, 158 Anaphylatoxins, 158, 170 Anatomical, 16, 158, 167, 188, 193, 197, 214 Androgens, 158, 172, 196 Anemia, 139, 158, 181, 198 Anesthesia, 158 Anesthetics, 158, 162, 178 Aneuploidy, 29, 158 Angiogenesis inhibitor, 31, 87, 100, 105, 108, 158, 177 Angiography, 17, 24, 158 Angiotensin converting enzyme inhibitor, 126, 158 Animal model, 12, 16, 17, 18, 24, 26, 28, 29, 80, 158, 222 Anionic, 9, 158 Anomalies, 16, 63, 117, 158, 220 Anthracycline, 158, 174 Anthrax, 11, 158 Antiangiogenesis, 29, 31, 102, 159 Antiangiogenic, 12, 13, 31, 35, 36, 38, 40, 63, 102, 159 Antibiotic, 11, 100, 159, 174, 176, 197, 204, 217, 220 Antibodies, 159, 184, 186, 187, 188, 206, 211 Antibody, 25, 42, 156, 159, 160, 169, 184, 185, 187, 188, 189, 198, 211, 215, 217 Anticoagulant, 159, 209, 225 Anticonvulsant, 159, 224 Antidote, 159, 192 Antifungal, 159, 216 Antigen, 25, 47, 109, 119, 156, 159, 160, 170, 174, 185, 187, 188, 189, 197, 215 Antigen-Antibody Complex, 159, 160, 170 Antigen-presenting cell, 159, 174 Anti-inflammatory, 22, 35, 98, 109, 119, 142, 159, 160, 172, 174, 175, 182, 208, 213 Anti-Inflammatory Agents, 159, 160, 172 Antimetabolite, 159, 181, 197 Antineoplastic, 156, 159, 165, 172, 173, 176, 181, 186, 190, 196, 197, 202, 216, 221, 224 Antineoplastic Agents, 156, 159, 224 Antioxidant, 14, 159, 202 Antipyretic, 159, 175, 211

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Antitumour, 52, 159 Antiviral, 108, 160, 188, 190 Anus, 160, 169 Aorta, 111, 160, 196 Aphthous Stomatitis, 96, 97, 160 Apolipoproteins, 160, 181, 193 Apoptosis, 7, 18, 22, 25, 31, 34, 74, 160, 166 Aqueous, 97, 160, 162, 173, 193 Arachidonic Acid, 110, 160, 192, 208 Arginine, 158, 160, 190 Arsenic trioxide, 29, 160 Arterial, 110, 119, 160, 167, 172, 187, 209 Arteries, 103, 111, 160, 161, 163, 165, 172, 192, 194, 196, 199, 206, 210, 221 Arterioles, 160, 163, 165, 197 Artery, 110, 160, 165, 167, 172, 177, 199, 203, 210, 212 Arthus Reaction, 103, 160, 187 Aspirin, 103, 126, 160 Assay, 7, 10, 29, 50, 87, 160 Astrocytes, 81, 160, 161, 195, 197, 198 Astrocytoma, 160, 182 Asymptomatic, 118, 161, 183 Ataxia, 138, 139, 161, 186, 220 Atherogenic, 16, 24, 161 Atrial, 161, 172, 225 Atrial Fibrillation, 161, 225 Atrophy, 138, 161, 179 Attenuated, 161, 175 Auditory, 108, 161 Autoimmune disease, 106, 118, 142, 161, 198 Autoimmunity, 142, 161 Autologous, 29, 46, 73, 81, 89, 90, 161 Autonomic Nervous System, 161, 204 Autosuggestion, 161, 187 Axons, 19, 161, 204 B Babesiosis, 161, 211 Bacillus, 11, 158, 161, 173 Bacteria, 159, 161, 162, 171, 177, 178, 197, 215, 217, 218, 222, 223 Bacterial Physiology, 155, 161 Bacterium, 161, 171 Barbiturate, 106, 161, 221 Basal Ganglia, 161, 162, 164, 181, 182 Basal Ganglia Diseases, 161, 162 Base, 27, 28, 162, 173, 191, 220 Basement Membrane, 99, 162, 179, 192 Benign, 106, 162, 164, 181, 184, 200, 211, 225 Benign tumor, 106, 162

Beta-pleated, 157, 162 Bilateral, 74, 162, 179, 203, 208 Bile, 118, 162, 167, 181, 185, 186, 191, 193, 218, 223 Bile Acids, 162, 218 Bile Acids and Salts, 162 Bile duct, 118, 162, 167 Bile Pigments, 162, 191 Biliary, 118, 162, 185 Bioavailability, 44, 56, 162 Biological response modifier, 62, 73, 162, 190 Biological therapy, 162, 184, 195 Biological Transport, 162, 175 Biomarkers, 15, 163 Biopsy, 163, 204 Biosynthesis, 160, 163, 194, 209, 216 Biotechnology, 32, 33, 116, 125, 135, 137, 138, 139, 163 Biotransformation, 68, 87, 163 Bladder, 163, 170, 189, 198, 209, 223 Blastocyst, 163, 170, 205 Blood Coagulation, 86, 99, 163, 165 Blood Coagulation Factors, 163 Blood Glucose, 103, 163, 184, 190 Blood pressure, 118, 163, 165, 187, 198, 207, 210, 216 Blood vessel, 8, 98, 105, 108, 111, 142, 158, 159, 163, 165, 167, 172, 177, 179, 191, 194, 196, 204, 208, 216, 218, 220, 221, 224 Blood Volume, 25, 163 Blood-Brain Barrier, 25, 163 Body Fluid Compartments, 6, 163 Body Fluids, 163, 176, 216, 222 Bone Marrow Cells, 26, 164, 195, 199 Bone Marrow Transplantation, 45, 47, 70, 73, 80, 89, 164 Bowel, 27, 104, 117, 118, 142, 164, 189, 191, 204, 218, 223 Brachial, 17, 24, 164 Brachytherapy, 164, 190, 211 Bradykinin, 164, 206 Brain Neoplasms, 164, 186, 221 Brain Stem, 16, 164 Bronchial, 164, 185 Bronchioles, 164 Bronchiolitis, 47, 164 Bronchiolitis Obliterans, 47, 164 Buccal, 164, 194, 218 C Cachexia, 63, 86, 164 Calcification, 17, 24, 164

229

Calcium, 104, 108, 126, 164, 170, 192, 197, 199, 203, 215 Camptothecin, 165, 191 Capillary, 9, 68, 99, 106, 164, 165, 224 Carbohydrate, 165, 172, 182, 183, 207 Carbon Dioxide, 165, 174, 180, 205, 213, 224 Carboplatin, 15, 25, 44, 165 Carboxy, 165 Carboxylic Acids, 98, 165 Carcinogen, 165, 196 Carcinogenic, 156, 165, 189, 208, 218 Carcinoma, 11, 63, 65, 113, 165 Cardiac, 66, 123, 161, 165, 168, 172, 178, 199, 218 Cardiovascular, 16, 24, 110, 165, 193 Cardiovascular disease, 16, 24, 165 Carmustine, 65, 121, 165 Carotid Arteries, 111, 165 Carrier Proteins, 165, 206 Case report, 5, 43, 46, 49, 60, 70, 90, 122, 165, 169 Case series, 165, 169 Caspase, 34, 166 Causal, 166, 178, 213 Cause of Death, 112, 166 Caustic, 166, 222 Cell Adhesion, 43, 166 Cell Adhesion Molecules, 43, 166 Cell Cycle, 166, 168, 173, 210 Cell Death, 160, 166, 200 Cell Differentiation, 166, 215 Cell Division, 138, 161, 166, 184, 190, 198, 206 Cell Hypoxia, 31, 166 Cell proliferation, 110, 166, 190, 215 Cell Survival, 11, 23, 166, 184 Cell Transplantation, 22, 24, 29, 46, 90, 166 Central Nervous System Infections, 166, 184, 186 Centrifugation, 166, 197 Ceramide, 82, 166 Cerebellar, 161, 166, 212 Cerebral, 25, 161, 162, 163, 164, 166, 167, 171, 178, 182, 186 Cerebral Cortex, 161, 166 Cerebral hemispheres, 162, 164, 167, 182 Cerebral Infarction, 167, 186 Cerebrospinal, 167, 186 Cerebrospinal fluid, 167, 186 Cerebrovascular, 162, 165, 167, 221 Cerebrum, 166, 167, 222

Cheilitis, 73, 167 Chemoprevention, 15, 167 Chemotactic Factors, 167, 170, 201 Chemotaxis, 29, 167 Chemotherapeutic agent, 25, 86, 167 Chemotherapeutics, 99, 167 Chenodeoxycholic Acid, 167, 223 Chin, 167, 196 Cholangitis, 118, 167 Choleretic, 167, 223 Cholesterol, 162, 167, 168, 172, 181, 192, 193, 194, 216, 218 Cholesterol Esters, 167, 193 Cholinergic, 98, 168 Chondrocytes, 168, 180 Chondrogenesis, 51, 168 Chromatin, 160, 168, 194 Chromosomal, 117, 158, 168, 220 Chromosome, 24, 29, 60, 158, 168, 171, 198, 220, 222, 223 Chronic Disease, 126, 164, 168, 192 Chronic renal, 168, 206 Chylomicrons, 168, 193 Cicatricial, 77, 168 Cicatrix, 168, 191 Cicatrix, Hypertrophic, 168, 191 Cinchona, 168, 211 Cirrhosis, 34, 118, 168, 207 CIS, 110, 168, 188 Cisplatin, 32, 113, 168 Clear cell carcinoma, 168, 175 Cleft Lip, 117, 168 Clinical Medicine, 168, 207 Clinical study, 17, 85, 168, 171 Cloning, 163, 169 Coagulation, 163, 169, 206, 225 Coenzyme, 169, 194, 216 Cofactor, 169, 209 Colchicine, 59, 73, 119, 126, 169 Colitis, 169 Collagen, 100, 162, 169, 180, 191, 206, 208 Colloidal, 156, 169, 177 Colon, 39, 87, 138, 169, 189, 192, 223 Colorectal, 54, 88, 124, 169 Colorectal Cancer, 54, 88, 124, 169 Combination chemotherapy, 13, 43, 56, 169 Combination Therapy, 108, 109, 118, 169 Complement, 103, 158, 160, 169, 170, 206, 215 Complementary and alternative medicine, 85, 91, 170

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Complementary medicine, 85, 170 Complete remission, 170, 212 Complete response, 4, 15, 170 Compliance, 20, 117, 170 Computational Biology, 135, 137, 170 Conception, 170, 180, 218 Concomitant, 12, 81, 90, 170 Conduction, 60, 170 Confounding, 22, 170 Congenita, 170, 211 Congestion, 170, 178 Conjugated, 162, 167, 170, 173 Conjugation, 110, 163, 170 Conjunctiva, 101, 171, 222 Connective Tissue Cells, 171 Consciousness, 157, 171, 174, 175 Consolidation, 23, 39, 171 Consolidation therapy, 23, 39, 171 Constriction, 171, 191 Contraindications, ii, 171 Contrast medium, 158, 171 Controlled clinical trial, 23, 171 Controlled study, 3, 4, 171 Conventional treatment, 23, 171 Convulsions, 159, 162, 171 Cooperative group, 26, 171 Coordination, 9, 24, 171, 198 Cor, 171 Cornea, 172, 214, 222, 223, 225 Corneum, 172, 178 Coronary, 17, 24, 111, 165, 172, 199 Coronary heart disease, 165, 172 Coronary Thrombosis, 172, 199 Corpus, 99, 111, 172, 208 Corpus Luteum, 99, 111, 172, 208 Corticosteroid, 172, 208, 218 Cortisone, 172, 174, 208 Cranial, 172, 184, 191, 200, 204 Craniocerebral Trauma, 162, 172, 184, 186, 221 Creatinine, 72, 173 Curative, 13, 173, 221 Cutaneous, 20, 40, 43, 57, 90, 96, 97, 112, 123, 126, 159, 173, 183, 187, 194 Cyclic, 173, 205, 209 Cyclin, 86, 173 Cyclodextrins, 80, 173 Cyclophosphamide, 5, 51, 126, 173 Cyclosporine, 68, 118, 119, 173, 188 Cysteine, 14, 173 Cystine, 173 Cytarabine, 34, 173

Cytidine, 21, 173 Cytochrome, 59, 173 Cytokinin, 96, 97, 173 Cytoplasm, 160, 173, 184, 194, 198 Cytosine, 173 Cytotoxic, 13, 21, 30, 173, 188, 211, 215 Cytotoxicity, 168, 174 D Daunorubicin, 34, 174, 176 Decarboxylation, 174, 185 Deception, 116, 174 Decidua, 174, 205 Degenerative, 174, 185 Deletion, 160, 174 Delivery of Health Care, 174, 182 Dementia, 70, 98, 122, 174 Dendrites, 174, 200 Dendritic, 13, 42, 109, 174, 196 Dendritic cell, 13, 42, 109, 174 Deoxycytidine, 21, 174 Depolarization, 174, 215 Depressive Disorder, 174, 193 Dermis, 174, 191 Desensitization, 174, 188 Detoxification, 87, 174 Dexamethasone, 7, 39, 41, 42, 51, 57, 59, 66, 76, 88, 96, 97, 174 Diabetes Mellitus, 103, 174, 183, 184 Diagnostic procedure, 95, 125, 175 Diarrhea, 89, 143, 175 Diclofenac, 52, 175 Diclofenac Sodium, 175 Diethylstilbestrol, 80, 175 Diffusion, 18, 162, 175, 189 Digestion, 156, 162, 164, 175, 191, 193, 218 Digestive tract, 97, 175, 216, 217, 225 Dihydrotestosterone, 175, 212 Dilation, 164, 175, 186 Dilution, 6, 175, 179, 206 Diploid, 158, 175, 198, 206, 222 Direct, iii, 6, 11, 14, 18, 102, 106, 122, 129, 168, 175, 176, 186, 211, 212 Discoid, 36, 101, 175 Discrete, 175, 193, 225 Disease Progression, 175, 224 Disposition, 10, 44, 175 Dissociation, 156, 175, 191 Distal, 175, 204, 210 Docetaxel, 53, 67, 86, 87, 88, 175 Dopamine, 176, 198, 200, 205 Dorsal, 176, 200, 207, 217 Double-blind, 3, 4, 56, 78, 176

231

Doxorubicin, 59, 66, 88, 113, 123, 176 Dronabinol, 143, 176, 220 Drug Interactions, 9, 130, 176 Drug Resistance, 29, 74, 176 Drug Tolerance, 176 Duct, 176, 179, 194, 213, 218 Duodenum, 162, 176, 218 Dura mater, 176, 196, 202 Dyes, 157, 176, 201 Dysplasia, 139, 176 Dystrophy, 138, 176 E Ectoderm, 176, 200 Ectopic, 20, 176 Effector, 155, 169, 176, 205 Efficacy, 4, 5, 13, 16, 18, 23, 25, 31, 38, 46, 54, 56, 57, 66, 96, 97, 103, 112, 118, 176 Elastic, 177, 217, 219 Elastin, 169, 177 Electrolyte, 172, 177, 207, 216 Electrons, 159, 162, 177, 191, 195, 202, 211 Electrophoresis, 9, 68, 177 Elementary Particles, 177, 195, 200, 209 Emboli, 177, 225 Embolism, 177, 210, 225 Embolization, 177, 225 Embryo, 14, 87, 98, 163, 166, 176, 177, 189, 196, 202, 225 Embryotoxicity, 14, 177 Emollient, 177, 183, 201 Encapsulated, 177, 193 Endoderm, 177, 225 Endogenous, 31, 96, 97, 106, 163, 176, 177 Endometrium, 99, 111, 174, 177 Endostatin, 31, 108, 110, 177 Endothelial cell, 99, 106, 163, 177, 180 Endothelium, 96, 97, 177, 178 Endothelium, Lymphatic, 177 Endothelium, Vascular, 177, 178 Endotoxin, 178, 223 End-stage renal, 168, 178, 206 Environmental Exposure, 178, 201 Environmental Health, 13, 134, 136, 178 Enzymatic, 165, 170, 178, 185 Enzyme, 165, 166, 169, 173, 176, 178, 183, 191, 194, 197, 198, 199, 204, 205, 206, 209, 212, 213, 215, 216, 219, 221, 222, 225 Enzyme Inhibitors, 178, 206 Epidemic, 78, 105, 178, 217 Epidemiologic Studies, 178, 182 Epidermal, 55, 67, 178, 193, 196, 225 Epidermis, 102, 172, 174, 178, 186, 193, 210

Epidermoid carcinoma, 178, 217 Epigastric, 178, 203 Epinephrine, 176, 178, 200, 223 Epithelial, 77, 113, 155, 162, 174, 178, 185, 192 Epithelium, 162, 177, 178, 225 Erythema, 4, 58, 96, 97, 101, 102, 106, 178 Erythema Nodosum, 4, 58, 96, 97, 101, 102, 106, 178 Erythrocyte Volume, 163, 179 Erythrocytes, 158, 161, 164, 179, 212, 215 Erythropoietin, 71, 179 Escalation, 23, 179 Esophageal, 63, 77, 179 Esophageal Ulcer, 77, 179 Esophagus, 97, 175, 179, 205, 218 Essential Tremor, 138, 179 Estrogen, 179, 196 Eukaryotic Cells, 179, 188, 202 Excitatory, 179, 183 Exfoliation, 179, 200 Exocrine, 179, 203 Exogenous, 103, 163, 177, 179 Exotoxins, 11, 179 Extensor, 179, 210 External-beam radiation, 179, 211 Extracellular, 6, 157, 160, 163, 171, 179, 180, 216 Extracellular Matrix, 171, 179, 180 Extravasation, 19, 25, 179 Extremity, 179, 203, 214 Exudate, 164, 179, 201 F Family Planning, 135, 180 Fat, 44, 143, 156, 160, 162, 163, 164, 166, 171, 172, 177, 180, 193, 198, 207, 216, 219 Fatigue, 142, 180, 184 Fatty acids, 110, 156, 165, 180, 208 Febrile, 56, 180 Fetal Blood, 180, 195 Fetus, 118, 179, 180, 205, 208, 223 Fibril, 22, 180 Fibrin, 163, 180, 221 Fibrinogen, 180, 206, 221 Fibroblast Growth Factor, 11, 40, 50, 102, 105, 113, 180 Fibroblasts, 72, 171, 180, 190 Fibrosis, 22, 118, 139, 180, 214 Fixation, 180, 215 Flatus, 180, 181 Flexor, 179, 181, 193 Fluorescence, 29, 181

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Fluorouracil, 113, 181, 193 Fold, 181, 196 Folic Acid, 181, 192 Forearm, 163, 181 Free Radicals, 104, 159, 175, 181, 199 Fungicide, 181, 185 G Gallbladder, 155, 162, 181 Gamma Rays, 181, 211 Ganglia, 155, 162, 181, 200, 204 Ganglion, 181, 200, 225 Gas, 9, 10, 165, 175, 180, 181, 186, 201, 224 Gastric, 181, 185, 197 Gastric Acid, 181, 197 Gastrin, 181, 185 Gastrointestinal, 44, 54, 87, 119, 126, 164, 178, 181, 193, 219, 222 Gastrointestinal tract, 126, 181, 193, 222 Gemfibrozil, 17, 181 Gene, 15, 16, 26, 30, 66, 116, 119, 139, 140, 163, 182, 201 Gene Expression, 16, 139, 182 Genetics, 23, 60, 171, 182 Genital, 4, 119, 142, 168, 182 Genotype, 16, 64, 182, 205 Geographic Locations, 12, 182 Germ Cells, 182, 202, 220, 225 Gestation, 60, 182, 205 Gland, 172, 182, 194, 203, 205, 209, 214, 221 Glioblastoma, 39, 69, 182 Glioblastoma multiforme, 39, 69, 182 Glioma, 25, 110, 182 Glomerular, 182, 212 Glomerulonephritis, 182, 187 Glucans, 173, 182 Glucocorticoid, 174, 182, 208 Gluconeogenesis, 182 Glucose, 103, 138, 163, 173, 174, 182, 183, 184, 190, 213 Glucose Intolerance, 174, 183 Glucuronic Acid, 183, 184 Glutamate, 183 Glutamic Acid, 101, 106, 181, 183, 200, 208 Glutathione Peroxidase, 183, 214 Glycerol, 6, 183, 205 Glycogen, 183 Glycols, 183, 186 Glycoprotein, 32, 37, 179, 180, 183, 192, 222 Gonadal, 183, 218 Gonorrhoea, 183, 202

Gout, 169, 183 Governing Board, 183, 207 Grade, 25, 31, 65, 75, 182, 183 Graft, 22, 38, 46, 50, 68, 70, 74, 96, 97, 183, 188, 199 Graft Rejection, 183, 188 Grafting, 183, 188 Graft-versus-host disease, 22, 38, 46, 50, 68, 70, 74, 183, 199 Granulation Tissue, 164, 184 Granulocytes, 184, 192, 215, 225 Growth factors, 7, 8, 45, 102, 104, 184, 197 Gynecologic oncologist, 18, 20, 184 H Haptens, 156, 184, 215 Headache, 184, 186 Heart attack, 165, 184 Heart failure, 44, 61, 66, 80, 123, 184 Hematologic malignancies, 28, 69, 184 Hematology, 11, 20, 27, 36, 55, 63, 64, 69, 73, 82, 90, 184 Hematopoiesis, 28, 184 Hemoglobin, 158, 179, 184, 192 Hemoglobinuria, 138, 184 Hemophilia, 117, 139, 184 Hemorrhage, 172, 184, 199, 210, 218 Heparin, 100, 184 Hepatic, 72, 156, 184, 193, 216 Hepatitis, 90, 118, 185 Hepatobiliary, 11, 185 Hepatocellular, 11, 44, 58, 71, 112, 113, 185 Hepatocellular carcinoma, 11, 44, 58, 71, 112, 113, 185 Hepatocytes, 185 Hereditary, 54, 183, 184, 185, 213 Heredity, 182, 185 Herpes, 32, 43, 185 Herpes Zoster, 185 Heterogeneity, 156, 185 Hexachlorobenzene, 80, 185 Histamine, 99, 158, 185 Histamine Agonists, 185 Histamine Antagonists, 99, 185 Histidine, 185, 190 Histiocytosis, 59, 185 Homologous, 173, 185, 215, 219 Hormonal, 161, 172, 185, 195 Hormonal therapy, 185, 195 Hormone therapy, 156, 185, 196 Horny layer, 178, 186 Humoral, 13, 183, 186, 188 Humour, 186

233

Hybrid, 186 Hybridization, 7, 186 Hybridomas, 186, 190 Hydrocephalus, 117, 186, 191 Hydrogen, 155, 157, 162, 165, 183, 186, 193, 198, 200, 201, 202, 210 Hydrogenation, 186, 211 Hydrolysis, 51, 98, 110, 111, 112, 163, 168, 186, 205, 207, 209 Hydrophobic, 9, 186, 193 Hydroxides, 186 Hydroxyl Radical, 104, 186 Hydroxylysine, 169, 186 Hydroxyproline, 169, 186 Hydroxyurea, 62, 186 Hyperalgesia, 19, 186 Hyperbilirubinemia, 186, 191 Hyperglycemia, 103, 187 Hyperkalaemia, 77, 187 Hyperplasia, 90, 187, 193 Hypersensitivity, 156, 174, 187, 193, 213, 215 Hypertension, 165, 187, 191, 207 Hypertrophy, 172, 187 Hypesthesia, 187, 200 Hypnotic, 98, 161, 187, 221 Hypoplasia, 64, 187 Hypoxia, 31, 47, 187, 221 I Iatrogenic, 31, 187 Idiopathic, 71, 74, 77, 187, 210, 214 Idiopathic myelofibrosis, 71, 187 Idiotype, 13, 187 Immune Complex Diseases, 103, 159, 187 Immune response, 108, 156, 159, 161, 172, 183, 184, 187, 188, 215, 219, 223, 225 Immune system, 23, 112, 159, 161, 162, 187, 188, 193, 195, 198, 223, 225 Immunity, 187, 190 Immunization, 187, 188, 215 Immunodeficiency, 3, 33, 71, 74, 138, 143, 187 Immunoglobulins, 187, 188, 206 Immunologic, 7, 38, 118, 167, 187, 188, 204, 211 Immunologic Diseases, 187, 188 Immunology, 42, 52, 74, 81, 156, 188 Immunomodulator, 106, 188 Immunophilins, 188, 216 Immunosuppressant, 96, 118, 156, 181, 188, 197, 216

Immunosuppression, 29, 96, 97, 118, 188, 194 Immunosuppressive, 5, 22, 118, 126, 142, 173, 182, 188, 220 Immunosuppressive Agents, 5, 118, 188 Immunosuppressive therapy, 188 Immunotherapy, 13, 162, 174, 188 Immunotoxins, 188, 211 Impairment, 113, 161, 188, 196 Implant radiation, 188, 190, 211 Implantation, 14, 111, 170, 188 In situ, 16, 29, 101, 188 In Situ Hybridization, 16, 29, 188 In vitro, 12, 14, 17, 23, 24, 28, 29, 43, 45, 52, 55, 58, 68, 74, 80, 82, 98, 102, 122, 189, 220 In vivo, 12, 14, 18, 28, 29, 52, 64, 80, 184, 189, 194, 220, 221 Incision, 189, 191 Incontinence, 186, 189 Induction, 8, 31, 80, 158, 171, 189, 216 Infarction, 167, 189, 206, 212 Infiltration, 38, 103, 182, 189, 225 Inflammation, 11, 14, 17, 19, 81, 101, 102, 108, 109, 118, 119, 142, 155, 156, 159, 160, 164, 167, 169, 179, 180, 185, 189, 193, 196, 200, 202, 203, 206, 209, 210, 217, 218, 220, 223, 224 Inflammatory bowel disease, 117, 119, 189 Infusion, 189, 199, 222 Ingestion, 62, 158, 189, 206 Inhalation, 12, 164, 189, 206 Initiation, 77, 189 Initiator, 189, 190 Innervation, 189, 204, 214, 221 Inorganic, 168, 186, 189, 198, 201 Insecticides, 189, 204 Insight, 12, 116, 189 Insomnia, 54, 189 Insulator, 189, 198 Insulin, 11, 14, 103, 190 Insulin-dependent diabetes mellitus, 190 Insulin-like, 11, 190 Interferon, 31, 32, 35, 52, 53, 58, 64, 68, 76, 108, 190 Interferon Alfa-2b, 68, 108, 190 Interferon-alpha, 190 Interleukin-1, 23, 102, 108, 110, 190 Interleukin-12, 23, 110, 190 Interleukin-2, 190 Interleukin-6, 66, 190 Interleukins, 188, 190

234

Thalidomide

Intermittent, 74, 119, 190 Internal Medicine, 4, 37, 80, 184, 190 Internal radiation, 190, 211 Interphase, 29, 190 Interstitial, 126, 164, 190, 191, 212 Intestinal, 17, 167, 191, 195, 225 Intestinal Mucosa, 17, 191, 225 Intestine, 162, 164, 169, 191, 192 Intracellular, 163, 189, 191, 207, 209, 214, 215 Intracranial Hemorrhages, 186, 191, 221 Intracranial Hypertension, 184, 186, 191 Intramuscular, 108, 191, 203 Intravenous, 54, 97, 108, 126, 189, 191, 203 Intrinsic, 156, 162, 191 Invasive, 18, 187, 191, 195 Involuntary, 143, 162, 179, 191, 199 Ion Channels, 160, 191 Ionization, 9, 191 Ions, 162, 175, 177, 186, 191, 216 Ipsilateral, 19, 191, 212 Irinotecan, 44, 54, 87, 88, 89, 107, 191 Ischemia, 104, 161, 191, 199, 212 Isozymes, 59, 191 J Jaundice, 118, 187, 191 Juvenile Delinquency, 117, 191 K Kb, 134, 191 Keloid, 100, 168, 191 Kidney Disease, 134, 139, 192 Kinetic, 6, 52, 192 L Labile, 169, 192 Laceration, 100, 192 Laminin, 162, 192 Large Intestine, 169, 175, 191, 192, 212, 216 Latent, 192, 208 LDL, 80, 181, 192, 194, 216 Leiomyosarcoma, 77, 192 Leprosy, 47, 60, 67, 76, 77, 101, 102, 106, 192 Lesion, 192, 194, 223 Lethargy, 186, 192 Leucine, 6, 192 Leucocyte, 157, 192 Leucovorin, 113, 192 Leukaemia, 46, 72, 192 Leukocyte Count, 69, 192 Leukopenia, 113, 192 Leukotrienes, 160, 192 Levamisole, 59, 193

Levo, 193, 196 Lichen Planus, 5, 45, 193 Ligament, 193, 209 Ligands, 166, 193 Lindane, 14, 193 Lip, 168, 193 Lipid, 6, 17, 25, 160, 181, 183, 190, 193, 198, 202 Lipid Peroxidation, 193, 202 Lipopolysaccharide, 107, 109, 193 Lipoprotein, 16, 24, 192, 193, 194 Liposomal, 34, 59, 66, 88, 193 Liquor, 193, 211 Lithium, 110, 193 Liver Cirrhosis, 113, 193 Liver Transplantation, 11, 193 Localization, 31, 194 Localized, 108, 157, 177, 180, 189, 192, 193, 194, 206, 214, 223 Lovastatin, 108, 194, 216 Low-density lipoprotein, 192, 193, 194 Lumbar, 194, 214, 221 Lupus, 36, 38, 57, 76, 77, 96, 97, 101, 112, 194, 220 Lye, 103, 194 Lymph, 177, 186, 194, 212, 214, 215 Lymph node, 194, 212, 214 Lymphatic, 107, 177, 189, 194, 196, 206, 216, 217, 221 Lymphatic system, 194, 216, 217, 221 Lymphocyte Depletion, 188, 194 Lymphocytes, 13, 32, 35, 109, 159, 174, 186, 187, 190, 192, 194, 199, 217, 220, 221, 225 Lymphocytic, 8, 28, 194 Lymphoid, 17, 159, 184, 192, 194 Lymphokine, 103, 194 Lymphoma, 35, 46, 54, 56, 67, 70, 81, 85, 86, 88, 89, 90, 138, 184, 194 Lytic, 195, 224 M Macroglia, 195, 197 Macrophage, 25, 190, 195 Magnetic Resonance Imaging, 18, 195 Magnetic Resonance Spectroscopy, 18, 195 Maintenance therapy, 23, 195 Malabsorption, 138, 195 Malaise, 103, 195 Malignancy, 8, 30, 76, 195 Malignant tumor, 113, 195, 198 Malnutrition, 14, 156, 161, 164, 195, 199

235

Mammogram, 164, 195, 197 Mania, 103, 195 Manic, 193, 195 Maternal-Fetal Exchange, 22, 195 Maxillary, 168, 195 Medial, 168, 195, 221 Mediate, 8, 166, 176, 195 Medical oncologist, 18, 195 MEDLINE, 135, 137, 139, 195 Medullary, 28, 195 Megakaryocytes, 164, 195 Megestrol, 143, 195, 196 Megestrol Acetate, 143, 196 Melanin, 196, 205, 223 Melanocytes, 196 Melanoma, 61, 64, 65, 68, 104, 105, 123, 124, 138, 196 Melphalan, 13, 24, 29, 76, 196 Memory, 174, 196 Meninges, 166, 172, 176, 196 Meningitis, 12, 33, 35, 183, 196 Mental, iv, 5, 16, 117, 134, 136, 140, 167, 174, 175, 180, 195, 196, 210, 215, 223 Mental Retardation, 16, 140, 196 Mentors, 11, 196 Mesenchymal, 7, 196 Mesenteric, 34, 111, 196, 207 Mesenteric Arteries, 111, 196 Mesentery, 196, 204 Mesoderm, 168, 196, 225 Metabolite, 33, 112, 163, 192, 194, 196, 207, 208 Metaplasia, 34, 38, 57, 60, 196 Metastasis, 102, 105, 107, 166, 196 Metastatic, 8, 53, 54, 61, 64, 65, 68, 76, 87, 88, 113, 164, 196, 214 Methotrexate, 118, 119, 126, 197 Methyltransferase, 15, 197 Micelle, 9, 197 Microbe, 197, 221 Microbiology, 43, 102, 155, 197 Microcalcifications, 164, 197 Microcirculation, 193, 197 Microglia, 44, 160, 197, 198 Microorganism, 169, 197, 225 Microscopy, 162, 197 Microsomal, 80, 197 Microtubules, 197, 202 Migration, 29, 81, 90, 168, 197 Milligram, 4, 197 Minocycline, 100, 197 Minority Groups, 26, 197

Misoprostol, 16, 197 Mitochondrial Swelling, 197, 200 Mitosis, 99, 160, 198 Mitotic, 175, 198 Mitotic inhibitors, 175, 198 Modification, 21, 198, 211 Molecular, 10, 13, 18, 24, 28, 45, 49, 59, 107, 135, 137, 163, 170, 180, 183, 184, 198, 223 Molecule, 54, 109, 159, 162, 169, 170, 173, 175, 176, 186, 198, 201, 202, 211, 215, 222, 224 Monitor, 18, 25, 173, 198, 201 Monoamine, 80, 198 Monoclonal, 22, 42, 85, 186, 188, 198, 211 Monocytes, 12, 102, 109, 190, 198, 221 Mononuclear, 17, 42, 51, 53, 107, 198, 223 Monosomy, 158, 198 Morphological, 80, 177, 196, 198 Morphology, 44, 184, 198 Motility, 62, 126, 198 Motion Sickness, 198, 200 Mucocutaneous, 4, 97, 119, 198 Mucosa, 119, 194, 198, 218 Mucus, 198, 223 Multicenter study, 66, 88, 198 Multiple sclerosis, 96, 198 Muscle Fibers, 199 Muscular Atrophy, 138, 199 Mutagenic, 156, 199 Mycophenolate mofetil, 118, 199 Myelin, 198, 199 Myelodysplasia, 24, 81, 90, 199 Myelofibrosis, 34, 38, 57, 60, 199 Myelogenous, 199 Myeloma, 7, 13, 22, 23, 29, 32, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 50, 51, 53, 54, 55, 56, 57, 58, 59, 60, 63, 64, 66, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 81, 85, 86, 87, 88, 89, 90, 122, 123, 124, 125, 142, 198, 199 Myocardial infarction, 104, 172, 199, 225 Myocardial Reperfusion, 199, 212 Myocardial Reperfusion Injury, 199, 212 Myocardium, 199 Myosin, 7, 199 Myotonia, 199, 211 Myotonic Dystrophy, 138, 199 N Natural killer cells, 190, 199 Nausea, 143, 176, 200, 223 NCI, 1, 19, 26, 133, 168, 200

236

Thalidomide

Necrolysis, 55, 67, 200 Necrosis, 14, 66, 78, 81, 82, 96, 97, 160, 167, 182, 189, 199, 200, 212, 214 Neoplasia, 107, 112, 138, 200 Neoplasm, 200, 214, 223 Nephropathy, 192, 200 Nervous System, 30, 98, 119, 138, 155, 161, 164, 166, 181, 182, 183, 193, 197, 198, 200, 204, 207 Neural, 14, 157, 186, 197, 200, 216 Neural Crest, 14, 200 Neuritis, 19, 103, 200 Neurofibroma, 64, 106, 200 Neurologic, 182, 186, 200 Neuroma, 106, 200 Neuronal, 104, 200, 204 Neurons, 174, 179, 181, 200, 219 Neuropathy, 53, 200, 204 Neurotransmitter, 155, 164, 176, 183, 185, 191, 200, 215, 219 Neutrons, 157, 200, 211 Neutrophil, 74, 103, 201 Neutrophil Activation, 103, 201 Nitrates, 104, 201 Nitric acid, 201 Nitrogen, 6, 156, 157, 158, 173, 180, 196, 201, 222 Nuclear, 28, 40, 162, 165, 171, 177, 179, 181, 182, 200, 201 Nuclei, 85, 157, 171, 177, 195, 198, 200, 201, 210 Nucleic acid, 173, 186, 188, 201 Nucleic Acid Hybridization, 186, 201 Nucleus, 160, 161, 162, 168, 173, 177, 179, 181, 194, 198, 200, 201, 210, 220 O Ocular, 59, 60, 62, 80, 101, 119, 201 Ointments, 100, 201 Oncogene, 86, 138, 201 Oncologist, 59, 88, 195, 201 Ophthalmic, 101, 201 Opiate, 99, 201 Opium, 201 Oral Health, 117, 201 Orchitis, 103, 202 Organelles, 166, 173, 196, 198, 202 Oropharynx, 3, 202 Osteogenesis, 168, 202 Osteoporosis, 90, 202 Ovarian Follicle, 172, 202 Ovaries, 202, 212, 215 Ovary, 172, 202, 218

Overall survival, 43, 202 Ovulation, 195, 202 Ovum, 172, 174, 182, 202, 208, 225 Oxidation, 6, 14, 155, 159, 163, 173, 183, 193, 202 Oxidation-Reduction, 163, 202 Oxidative Stress, 14, 202 Oxytocic, 197, 202 P Pachymeningitis, 196, 202 Paclitaxel, 15, 39, 81, 87, 88, 202 Palate, 117, 203, 218 Palliative, 66, 76, 195, 203, 221 Pamidronate, 24, 61, 203 Pancreas, 103, 155, 163, 190, 203, 222 Pancreatic, 138, 203 Pancreatic cancer, 138, 203 Panniculitis, 34, 203 Papilla, 203 Papillary, 63, 203 Paradoxical, 81, 90, 203 Parenteral, 97, 103, 203 Paresis, 200, 203 Paresthesias, 200, 203 Parotid, 203, 214 Paroxysmal, 138, 203 Partial remission, 13, 48, 203, 212 Partial response, 203 Particle, 197, 203, 217, 222 Pathologic, 160, 163, 172, 186, 187, 203, 210, 212 Pathologic Processes, 160, 203 Patient Education, 142, 148, 150, 153, 203 Patient Participation, 27, 203 Pelvic, 100, 203, 209 Pelvis, 192, 194, 202, 203, 204, 223 Penicillamine, 59, 126, 204 Penicillin, 204, 224 Pentoxifylline, 34, 60, 81, 96, 204 Pepsin, 197, 204 Peptide, 180, 204, 207, 209 Percutaneous, 64, 106, 204 Perfusion, 25, 187, 204 Pericardium, 204, 220 Pericytes, 99, 204 Peripheral blood, 10, 23, 29, 42, 53, 107, 190, 204 Peripheral Nerves, 192, 204, 217 Peripheral Nervous System, 98, 200, 204, 219 Peripheral Neuropathy, 98, 204 Peripheral stem cells, 184, 204

237

Peritoneal, 63, 204 Peritoneum, 196, 204 Perivascular, 197, 204 Peroneal Nerve, 204, 214 Pesticides, 14, 189, 204 Phagocytosis, 197, 205 Pharmacist, 12, 205 Pharmacodynamic, 10, 30, 54, 205 Pharmacokinetic, 10, 54, 71, 205 Pharmacologic, 28, 30, 158, 205, 221 Pharynx, 202, 205 Phenotype, 16, 17, 24, 205 Phenylalanine, 205, 223 Phocomelia, 98, 112, 205 Phorbol, 82, 205 Phosphodiesterase, 204, 205 Phospholipases, 205, 215 Phospholipids, 180, 193, 205 Phosphorus, 164, 205 Phosphorylation, 21, 205 Physiologic, 156, 163, 205, 208, 212 Physiology, 31, 66, 184, 205 Pigment, 196, 205 Pilot study, 23, 34, 38, 63, 116, 205 Pituitary Gland, 172, 180, 205 Placenta, 99, 111, 180, 205, 208 Plant Oils, 201, 206 Plants, 156, 157, 165, 182, 198, 206, 207, 213, 222 Plaque, 161, 206 Plasma cells, 7, 22, 159, 184, 198, 199, 206 Plasma protein, 98, 156, 177, 206 Plasma Volume, 163, 206 Platelet Activation, 206, 215 Platelet Aggregation, 99, 158, 204, 206, 221 Platelets, 195, 206, 221 Plexus, 206, 214 Pneumonia, 164, 171, 206 Poisoning, 200, 206 Polyarteritis Nodosa, 187, 206 Polycystic, 139, 206 Polymers, 9, 206, 209 Polymorphic, 26, 168, 206 Polymorphism, 25, 206 Polypeptide, 169, 180, 186, 207 Polyposis, 169, 207 Polysaccharide, 159, 207, 209 Polyunsaturated fat, 110, 207, 221 Pons, 164, 207 Portal Hypertension, 34, 118, 207 Portal Vein, 207 Posterior, 161, 176, 203, 207, 214

Postmenopausal, 202, 207 Postsynaptic, 207, 215 Post-translational, 21, 207 Potassium, 59, 110, 187, 194, 207 Potentiates, 190, 207 Potentiating, 109, 110, 207 Potentiation, 207, 215 Practice Guidelines, 136, 207 Pravastatin, 108, 207 Precipitation, 67, 207 Preclinical, 31, 66, 207 Precursor, 14, 22, 112, 160, 168, 173, 176, 178, 205, 207, 208, 222, 223, 224 Predisposition, 29, 117, 208 Prednisolone, 208 Prednisone, 5, 34, 68, 208 Prenatal, 177, 208 Presbycusis, 108, 208 Prevalence, 119, 208 Primary tumor, 15, 208 Prodrug, 112, 208 Progeny, 50, 171, 208 Progesterone, 195, 208, 218 Prognostic factor, 15, 208 Progression, 11, 23, 66, 122, 158, 208, 222 Progressive, 22, 29, 39, 40, 50, 70, 72, 166, 168, 174, 176, 179, 187, 199, 200, 206, 208, 212, 223 Progressive disease, 22, 187, 208 Proliferative Retinopathy, 90, 208 Proline, 169, 186, 208 Promoter, 15, 25, 66, 208 Prone, 100, 208 Prophylaxis, 109, 208, 213, 223, 225 Propionic Acids, 98, 208 Prospective study, 53, 208 Prostaglandin, 197, 208, 221 Prostaglandins A, 99, 209 Prostaglandins D, 209 Prostate, 27, 36, 53, 67, 81, 86, 87, 88, 113, 122, 138, 163, 209, 222 Protease, 16, 24, 169, 209 Protease Inhibitors, 16, 24, 209 Protein C, 156, 160, 193, 209, 215 Protein S, 6, 116, 139, 163, 209, 220 Proteinuria, 198, 209 Proteoglycans, 162, 209 Proteolytic, 157, 170, 180, 209 Protocol, 12, 19, 26, 209 Protons, 157, 186, 195, 209, 211 Proto-Oncogene Proteins, 202, 210 Proto-Oncogene Proteins c-mos, 202, 210

238

Thalidomide

Protozoa, 171, 197, 210 Proximal, 18, 175, 210 Pruritic, 193, 210 Psoriasis, 46, 210, 213 Psychic, 196, 210, 214 Public Policy, 135, 210 Publishing, 32, 210 Pulmonary, 67, 70, 81, 88, 126, 163, 172, 193, 210, 219, 225 Pulmonary Artery, 163, 210 Pulmonary Embolism, 210, 225 Pulmonary hypertension, 70, 126, 172, 210 Pulse, 198, 210 Purpura, 34, 210 Purulent, 183, 210 Pyoderma, 23, 68, 96, 97, 210 Pyoderma Gangrenosum, 68, 96, 97, 210 Pyogenic, 106, 210 Q Quality of Life, 3, 211, 219 Quinine, 99, 168, 211 Quinolones, 118, 211 R Race, 9, 98, 196, 197, 211 Racemic, 9, 98, 196, 211 Radiation, 18, 20, 27, 31, 107, 156, 177, 178, 179, 181, 188, 190, 201, 211, 213, 225 Radiation oncologist, 18, 20, 201, 211 Radiation therapy, 31, 107, 156, 179, 190, 211, 213 Radioactive, 186, 188, 190, 191, 201, 211 Radioimmunotherapy, 40, 211 Radiolabeled, 10, 211 Radiological, 204, 211 Radiotherapy, 15, 80, 164, 211 Randomized, 3, 4, 7, 13, 34, 55, 56, 68, 86, 177, 211 Receptor, 17, 20, 24, 28, 99, 108, 155, 159, 176, 211, 215 Recombinant, 190, 212, 224 Recombination, 171, 212 Rectum, 160, 169, 175, 180, 181, 189, 192, 209, 212 Recurrence, 25, 68, 74, 100, 125, 167, 212 Red blood cells, 179, 187, 212, 214 Red Nucleus, 161, 212 Reductase, 108, 194, 197, 207, 212, 216 Refer, 1, 164, 169, 180, 185, 194, 200, 211, 212 Refractory, 7, 34, 44, 46, 48, 51, 56, 57, 60, 66, 70, 71, 72, 75, 76, 81, 88, 89, 90, 113, 121, 124, 212

Regeneration, 19, 180, 212 Regimen, 55, 124, 176, 212 Regional lymph node, 107, 212 Relapse, 13, 212 Relaxin, 126, 212 Remission, 31, 40, 113, 124, 195, 212 Renal cell cancer, 123, 124, 212 Renal cell carcinoma, 40, 53, 65, 69, 76, 212 Renal failure, 77, 212 Reperfusion, 104, 199, 212 Reperfusion Injury, 104, 212 Resorption, 186, 212 Respiration, 165, 198, 213 Retina, 208, 213, 223 Retinoblastoma, 138, 213 Retinoids, 73, 213 Retrospective, 29, 213 Retrospective Studies, 29, 213 Rheology, 204, 213 Rheumatoid, 96, 97, 113, 119, 213 Rheumatoid arthritis, 96, 97, 113, 119, 213 Ribonucleoside Diphosphate Reductase, 186, 213 Ribose, 173, 213 Risk factor, 15, 29, 53, 89, 178, 208, 213 Rodenticides, 204, 213 S Salicylate, 213 Salicylic, 213 Salicylic Acids, 213 Salivary, 203, 213 Salvage Therapy, 57, 81, 89, 213 Saponins, 213, 218 Sarcoidosis, 23, 43, 73, 90, 123, 214 Sarcoma, 35, 46, 58, 214 Scabicide, 193, 214 Sciatic Nerve, 19, 204, 214, 221 Sclera, 171, 214, 223 Scleroderma, 22, 52, 75, 126, 214 Sclerosis, 138, 198, 214 Screening, 10, 15, 169, 214 Secondary tumor, 196, 214 Secretion, 8, 23, 70, 172, 185, 186, 190, 197, 198, 214 Sedative, 30, 98, 105, 112, 161, 214 Seizures, 182, 203, 214 Selection Bias, 22, 214 Selenium, 108, 214 Semen, 209, 214 Semisynthetic, 165, 188, 197, 215 Senescence, 29, 215 Senile, 98, 202, 208, 215

239

Sensibility, 157, 186, 215 Sensitization, 20, 215 Sepsis, 32, 45, 215 Septic, 81, 215 Serous, 63, 177, 215 Serum, 15, 67, 72, 81, 85, 98, 103, 156, 158, 169, 181, 187, 192, 194, 215, 222 Serum Sickness, 187, 215 Sex Characteristics, 158, 215, 220 Sex Determination, 139, 215 Shock, 10, 11, 81, 215, 222 Side effect, 5, 6, 41, 69, 98, 107, 129, 143, 156, 162, 173, 215, 219, 221 Signal Transduction, 10, 18, 86, 215 Signs and Symptoms, 206, 212, 215 Simvastatin, 108, 216 Single-agent, 13, 70, 89, 216 Sirolimus, 118, 188, 216 Skeletal, 80, 158, 198, 216 Skeleton, 155, 208, 216 Skin graft, 48, 216, 218 Skull, 172, 216, 220 Small intestine, 36, 167, 168, 176, 185, 191, 216, 224 Smooth muscle, 158, 171, 185, 204, 216, 219 Social Environment, 211, 216 Social Problems, 117, 216 Sodium, 110, 175, 183, 194, 211, 216, 224 Sodium Channels, 211, 216, 224 Soft tissue, 163, 216 Solid tumor, 8, 34, 69, 105, 158, 176, 177, 216 Solvent, 183, 216 Somatic, 186, 198, 204, 216, 220 Somatic cells, 198, 216 Somnolence, 4, 98, 216 Sound wave, 170, 217 Soybean Oil, 207, 217 Specialist, 144, 175, 217 Species, 14, 104, 157, 161, 166, 169, 173, 178, 186, 197, 198, 211, 217, 218, 219, 222, 224, 225 Specificity, 156, 217 Spectroscopic, 17, 18, 25, 195, 217 Spectrum, 197, 217 Sperm, 158, 168, 217 Spinal cord, 104, 160, 164, 166, 167, 176, 181, 196, 200, 202, 204, 214, 217 Spinal Nerves, 204, 217 Spinous, 178, 217 Spleen, 157, 194, 214, 217

Splenomegaly, 57, 217 Spondylitis, 61, 63, 121, 123, 217 Sporadic, 213, 217 Sputum, 15, 217 Squamous, 15, 87, 178, 217 Squamous cell carcinoma, 15, 87, 178, 217 Squamous cells, 217 Stabilization, 50, 72, 218 Staging, 24, 218 Staphylococcus, 197, 218 Stem Cells, 157, 179, 204, 218 Stenosis, 110, 218 Stents, 110, 111, 218 Sterility, 173, 218 Steroid, 99, 100, 123, 162, 172, 213, 216, 218 Steroid therapy, 123, 218 Stimulant, 185, 218, 224 Stomach, 155, 175, 179, 181, 185, 200, 204, 205, 216, 217, 218 Stomatitis, 96, 97, 218 Stool, 169, 189, 192, 218 Stress, 14, 16, 24, 31, 161, 200, 202, 208, 213, 218 Stricture, 218 Stroke, 104, 134, 165, 218 Stromal, 24, 29, 164, 218 Stromal Cells, 164, 218 Structure-Activity Relationship, 52, 218 Subacute, 189, 219 Subclinical, 16, 24, 189, 214, 219 Subcutaneous, 108, 203, 219 Subspecies, 217, 219 Substance P, 196, 214, 219 Substrate, 6, 178, 219 Supplementation, 14, 219 Support group, 17, 25, 219 Supportive care, 69, 219 Suppression, 28, 41, 53, 96, 97, 172, 219 Suppressive, 4, 219 Suppurative, 118, 183, 219 Surfactant, 9, 219 Survival Rate, 202, 219 Symphysis, 167, 209, 219 Symptomatic, 34, 219 Symptomatology, 16, 219 Synaptic, 200, 215, 219 Synergistic, 6, 219 Syphilis, 202, 219 Systemic disease, 12, 220 Systemic lupus erythematosus, 25, 96, 187, 220 Systemic therapy, 113, 220

240

Thalidomide

T Tacrolimus, 118, 188, 220 Telangiectasia, 54, 139, 220 Telomerase, 29, 220 Telomere, 29, 220 Temozolomide, 39, 61, 65, 68, 123, 220 Temporal, 20, 220 Teratogen, 101, 220 Teratogenesis, 33, 51, 58, 61, 87, 220 Teratogenic, 12, 14, 22, 30, 58, 61, 98, 101, 156, 220 Teratogenicity, 13, 59, 80, 98, 220 Testis, 202, 220 Testosterone, 143, 212, 220 Tetracycline, 197, 220 Tetrahydrocannabinol, 176, 220 Thalamic, 161, 220 Thalamic Diseases, 161, 220 Therapeutics, 28, 29, 31, 34, 46, 56, 63, 67, 89, 106, 130, 221 Thigh, 19, 221 Thrombin, 180, 206, 209, 221 Thromboembolism, 53, 87, 221 Thrombolytic, 104, 221 Thrombopenia, 113, 221 Thrombosis, 41, 47, 53, 77, 86, 87, 89, 123, 209, 218, 221 Thromboxanes, 160, 221 Thymus, 187, 194, 221 Thyroid, 221, 223 Tibial Nerve, 214, 221 Tooth Preparation, 155, 221 Topical, 5, 93, 101, 102, 119, 142, 221 Topoisomerase inhibitors, 107, 191, 221 Topotecan, 34, 221 Toxicity, 3, 14, 54, 67, 72, 76, 86, 87, 88, 105, 176, 221 Toxicology, 13, 43, 59, 136, 221 Toxins, 11, 159, 179, 183, 188, 189, 211, 222 Trachoma, 106, 222 Transcriptase, 220, 222 Transduction, 20, 30, 215, 222 Transfection, 26, 163, 222 Transfusion, 71, 222 Translational, 8, 11, 29, 222 Translocation, 28, 222 Transmitter, 155, 160, 176, 191, 222 Transplantation, 13, 29, 68, 73, 81, 168, 187, 194, 222 Trauma, 100, 108, 200, 222 Trichloroacetic Acid, 67, 222 Trisomy, 158, 222

Tryptophan, 169, 222 Tuberculosis, 12, 38, 60, 106, 194, 202, 213, 222 Tuberous Sclerosis, 139, 222 Tumor marker, 15, 163, 222 Tumor model, 18, 222 Tumor Necrosis Factor, 32, 37, 66, 102, 106, 110, 111, 119, 221, 222 Tumor suppressor gene, 15, 24, 223 Tumour, 66, 75, 78, 81, 82, 96, 97, 122, 159, 181, 223 Tunica, 198, 223 Tyrosine, 28, 176, 223 U Ulcer, 4, 179, 184, 197, 223 Ulceration, 3, 4, 119, 223 Ulcerative colitis, 117, 119, 189, 210, 223 Univalent, 186, 202, 223 Unresectable, 11, 223 Uremia, 212, 223 Urethra, 209, 223 Urinary, 80, 186, 189, 223 Urine, 8, 163, 173, 184, 189, 209, 212, 223 Ursodeoxycholic Acid, 118, 223 Uterus, 172, 174, 177, 192, 202, 208, 223 Uvea, 223 Uveitis, 74, 223 V Vaccination, 13, 100, 223 Vaccine, 156, 209, 223 Vagina, 175, 223 Valine, 204, 224 Valproic Acid, 16, 80, 224 Varicella, 32, 43, 224 Vascular, 8, 11, 16, 22, 25, 28, 111, 113, 119, 160, 174, 177, 178, 184, 189, 193, 197, 202, 205, 223, 224 Vascular endothelial growth factor, 11, 28, 224 Vasculitis, 96, 97, 103, 206, 224 Vasodilator, 164, 176, 185, 199, 224 Vector, 222, 224 Vein, 41, 53, 87, 89, 123, 191, 201, 203, 207, 224 Venous, 41, 53, 77, 87, 97, 119, 167, 192, 209, 224, 225 Venous blood, 167, 192, 224 Venous Thrombosis, 41, 224, 225 Ventricles, 167, 186, 224 Ventricular, 172, 186, 199, 224 Venules, 163, 165, 177, 197, 224 Vertebrae, 217, 224

241

Vesicular, 185, 197, 224 Veterinary Medicine, 135, 224 Villi, 186, 224 Vinca Alkaloids, 224 Vincristine, 59, 66, 88, 224 Viral, 17, 195, 222, 224, 225 Viral Load, 17, 224 Virulence, 161, 221, 224 Virulent, 12, 224 Virus, 3, 32, 33, 43, 71, 74, 143, 166, 190, 206, 222, 224, 225 Visceral, 14, 22, 161, 204, 225 Vitelline Membrane, 225 Vitro, 12, 17, 24, 29, 32, 51, 102, 184, 225 Vivo, 28, 33, 51, 194, 225 Volition, 191, 225

W Warfarin, 10, 225 Warts, 222, 225 White blood cell, 10, 159, 192, 194, 195, 198, 199, 201, 206, 225 Wound Healing, 99, 111, 166, 168, 180, 225 X Xenograft, 39, 87, 158, 222, 225 Xenopus, 87, 225 X-ray, 171, 181, 195, 201, 211, 225 Y Yeasts, 205, 225 Yolk Sac, 14, 225 Z Zoster, 32, 43, 225 Zygote, 170, 171, 225

242

Thalidomide

243

244

Thalidomide

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