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

KERATOSIS 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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KERATOSIS 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., 1960Keratosis: 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: 0-597-84590-5 1. Keratosis-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 keratosis. 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 KERATOSIS ................................................................................................ 3 Overview........................................................................................................................................ 3 Federally Funded Research on Keratosis........................................................................................ 3 E-Journals: PubMed Central ....................................................................................................... 16 The National Library of Medicine: PubMed ................................................................................ 16 CHAPTER 2. NUTRITION AND KERATOSIS ...................................................................................... 61 Overview...................................................................................................................................... 61 Finding Nutrition Studies on Keratosis ...................................................................................... 61 Federal Resources on Nutrition ................................................................................................... 64 Additional Web Resources ........................................................................................................... 64 CHAPTER 3. ALTERNATIVE MEDICINE AND KERATOSIS ................................................................ 67 Overview...................................................................................................................................... 67 National Center for Complementary and Alternative Medicine.................................................. 67 Additional Web Resources ........................................................................................................... 70 General References ....................................................................................................................... 71 CHAPTER 4. CLINICAL TRIALS AND KERATOSIS ............................................................................. 73 Overview...................................................................................................................................... 73 Recent Trials on Keratosis ........................................................................................................... 73 Keeping Current on Clinical Trials ............................................................................................. 76 CHAPTER 5. PATENTS ON KERATOSIS ............................................................................................. 79 Overview...................................................................................................................................... 79 Patents on Keratosis..................................................................................................................... 79 Patent Applications on Keratosis................................................................................................. 92 Keeping Current .......................................................................................................................... 97 CHAPTER 6. BOOKS ON KERATOSIS................................................................................................. 99 Overview...................................................................................................................................... 99 Book Summaries: Federal Agencies.............................................................................................. 99 The National Library of Medicine Book Index ........................................................................... 100 Chapters on Keratosis ................................................................................................................ 101 CHAPTER 7. PERIODICALS AND NEWS ON KERATOSIS ................................................................. 103 Overview.................................................................................................................................... 103 News Services and Press Releases.............................................................................................. 103 Academic Periodicals covering Keratosis ................................................................................... 105 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 107 Overview.................................................................................................................................... 107 U.S. Pharmacopeia..................................................................................................................... 107 Commercial Databases ............................................................................................................... 108 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 111 Overview.................................................................................................................................... 111 NIH Guidelines.......................................................................................................................... 111 NIH Databases........................................................................................................................... 113 Other Commercial Databases..................................................................................................... 115 The Genome Project and Keratosis............................................................................................. 115 APPENDIX B. PATIENT RESOURCES ............................................................................................... 121 Overview.................................................................................................................................... 121 Patient Guideline Sources.......................................................................................................... 121 Finding Associations.................................................................................................................. 125 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 127 Overview.................................................................................................................................... 127 Preparation................................................................................................................................. 127

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Finding a Local Medical Library................................................................................................ 127 Medical Libraries in the U.S. and Canada ................................................................................. 127 ONLINE GLOSSARIES................................................................................................................ 133 Online Dictionary Directories ................................................................................................... 134 KERATOSIS DICTIONARY........................................................................................................ 135 INDEX .............................................................................................................................................. 193

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

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

Project Title: A TRANSGENIC ANIMAL MODEL FOR PEMPHIGOID Principal Investigator & Institution: Yancey, Kim B.; Professor and Chair; Dermatology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Pemphigoid represents a group of subepidermal blistering diseases characterized by autoantibodies against components of

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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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hemidesmosomes, organelles in basal keratinocytes that promote adhesion of epidermis to basement membrane (BM). Bullous pemphigoid antigen 2 (BPAG2), a type II transmembrane protein in hemidesmosomes, is a major autoantigen bound by such patients' autoantibodies. Our hypothesis is that autoantibodies against BPAG2 are pathogenic, that T cells provide crucial signals for production of such antibodies, and that antagonism of such antigen-specific T cells will abrogate production of pathogenic antibodies. To test this hypothesis, transgenic (Tg) mice expressing human BPAG2 (hBPAG2) in murine epidermal BM have been produced. Our goals are to use these mice to: a) assess the pathogenic activity of patient anti-hBPAG2 autoantibodies in vivo; b) elicit and characterize model immune responses of B and T cells to hBPAG2; c) develop an experimental animal model that mimics pemphigoid; and d) identify interventions that may modulate or antagonize immune responses to hBPAG2. Preliminary studies indicate that grafting hBPAG2 Tg skin onto syngeneic wild type mice elicits production of anti-hBPAG2 IgG that targets the same portion of this antigen that is bound by autoantibodies and T cell lines from patients with pemphigoid. Anti-hBPAG2 IgG did not develop in MHC class II -/- mice grafted with hBPAG2 Tg skin indicating that cognate interactions between T cell receptor/peptide-class II MHC determinants appear to be crucial for antigen-specific IgG production in this model. Preliminary studies also indicate that such antigen-specific responses in "immunized" wild type mice can be adoptively transferred to Tg mice expressing the antigen of interest (i.e., hBPAG2) in a tissue-specific and biologically relevant site in vivo (i.e., epidermal BM). Moreover, patient anti-BPAG2 autoantibodies bind epidermal BM in Tg skin, thus supporting the hypothesis that such mice can be used to assess the pathogenic activity of patient autoantibodies in vivo. Studies outlined in this proposal will build upon these observations to define primary immune responses to BPAG2, identify ways to block such responses, and develop relevant animal models of immunobullous diseases in which basic pathomechanisms can be defined and novel therapeutic interventions can be explored, tested, and refined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL ADHESION AND CYTOSKELETAL DYNAMICS IN SKIN Principal Investigator & Institution: Fuchs, Elaine V.; Professor; Lab/Mammalian Cell/Dev Biology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2004; Project Start 01-DEC-1980; Project End 30-NOV-2008 Summary: (provided by applicant): Our global objective is to develop a molecular understanding of epithelial stem cell lineages and morphogenesis in mammalian skin, and bring this research to a clinical setting. Our focus is on how skin stem ceils utilize cytoskeletal connections to intercellular junctions. Knowledge of the proteins involved in linking the actin filament (AF) cytoskeleton to adherens junctions (AJs), and elucidating how these connections are regulated are key to understanding how selfrenewing skin epithelium maintains a surface barrier and how a stem cell can give rise to a hair follicle (HF). Elucidating how microtubules (MTs) link to AJs is important for understanding how the stratified epidermis maintains a single layer of dividing cells, and how spindle polarity changes when stem cells are activated to produce HFs. To examine cytoskeletal-junction dynamics during epidermal homeostasis and woundhealing, mice displaying fluorescently labeled AFs, MTs and AJs will be engineered, and used to derive three dimensional epidermal cultures. A molecular understanding of these dynamics will be obtained by focusing on two cytoskeletal-junction linking proteins that surfaced as being key from our prior studies: beta-catenin, which links AFs and AJs, and ACF7, which can bind MTs and link them to intercellular junctions.

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Through yeast two-hybrid screens, biochemical and molecular approaches, alphacatenin and ACF7's interacting partners will be defined and characterized. Through mouse genetics, the functional significance of their varied associations will be ascertained. Finally, as the major players in these processes unfold, microarray analyses will be conducted, to define global changes in AJ-cytoskeletal gene expression that occur concomitantly as stem cells receive external cues to remodel their AJ-cytoskeletal connections and initiate HFs. Understanding how these cytoskeletal linkages are regulated in normal skin is a prerequisite to elucidating how defects in these processes lead to genetic disorders, including skin cancers. Past and present AR27883 research provides an excellent illustration of how molecular skin biology can help to generate new and improved tools for the diagnosis and treatment for human skin disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLASS I MOLECULES AND AUTOIMMUNITY Principal Investigator & Institution: Roopenian, Derry C.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 01-MAY-1999; Project End 31-JUL-2007 Summary: (provided by applicant): IgG is the major antibody isotype responsible for a wide diversity of autoimmune diseases. A major goal would thus be to understand how one controls the levels of pathogenic IgG antibodies in individuals with autoimmune disease. Studies culminating in our recent gene targeting and transgenic experiments have suggested that the MHC class I-like IgG protection receptor, FcRn, plays a key role in maintaining endogenous IgG concentrations in mammals of all ages. Our studies indicate that FcRn is a key control point for IgG-mediated immune responses. The overall goal of the proposed studies is thus to elucidate the biology and function of FcRn in normal and autoimmune states. Our new results provide the first direct evidence that FcRn is an important molecule for humoral autoimmunity. Aim 1 will determine which autoimmune diseases are ameliorated (or exacerbated) by an FcRn deficiency in a variety of autoimmune diseases. The results will suggest the diseases in which increased serum IgG concentrations are deleterious or protective. In doing so, it should define the autoimmune diseases that might be amenable to anti-FcRn therapeutic strategies. While FcRn protein is detected only at low levels in healthy adult mice, our new results indicate that FcRn protein increases substantially as mice develop SLE. Aim 2 will thus determine whether an increased level of FcRn expression contributes to autoimmune disease. These results should provide important insights into why FcRn is upregulated and whether FcRn upregulation is a major factor in establishing and maintaining hypergammaglobulinemia. While the IgG conserving function of FcRn is well established, the difficulties in monitoring FcRn in vivo have impeded the resolution of major issues concerning its in vivo biology. To determine the tissue sites in which FcRn expresses and operates to protect IgG from catabolism under normal and autoimmune situations, Aim 3 will thus employ Cre-Lox technology to replace the normal FcRn gene with an FcRn-GFP fusion construct. The expression of this construct under normal regulation and under tissue specific regulation will clarify the anatomy of FcRnmediated protection of IgG, and, more generally, will facilitate many other aspects of investigation into the physiology of FcRn. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORNIFIED ENVELOPE PERMEABILITY BARRIER FUNCTION

ASSOCIATED

PROTEINS

AND

Principal Investigator & Institution: Elias, Peter M.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002 Summary: Although the role of structural proteins in the epidermal mechanical barrier is clear, their role in the permeability barrier is unknown. We hypothesize that selected structural and enzymatic proteins; i.e., those that are both regulated by Ca++ and associated with the cornified envelope (CE): involucrin, loricrin, transglutaminase 1 (TG1), pro-fillaggrin, and K1/10, are regulated/required for barrier homeostasis. This proposal will assess which of these proteins are regulated by permeability barrier requirements, and how these CE-associated proteins, in partnership with the lipid bound envelope (LBE) and the lipid-enriched extracellular lamellae, from the permeability barrier. Specifically, in Aim #1 we will determine which CE- associated proteins are regulated by altered barrier requirements, and whether Ca++ regulates their expression, by: a) measuring the time course of mRNA/protein expression for the CE-associated proteins after acute barrier disruption (acetone, tape stripping) and in essential fatty acid deficiency (EFAD) in hairless mice. b) Ascertaining whether changes in extracellular Ca++ (in vivo by sonophoresis and by immersion) modulate expression of the regulated CE protein(s); and the participation of the calcium receptor (CaR) and voltage-sensitive Ca++ channels in these changes. c) Determining whether the transient decrease in CE-associated protein expression facilitates barrier recovery. Using three transgenic over- expressing (involucrin, K6/16, and pro-filaggrin) murine models, and one of these proteins interferes with permeability barrier homeostasis and lamellar body secretion. In Aim #2, we will determine which CE-associated proteins are required for normal barrier homeostasis, and the mechanisms by which alterations in these proteins lead to barrier abnormalities, by: a) Assessing homeostasis in human and murine models with specific deletions or mutations of CE-associated proteins; i.e., in patients with lamellar ichthyosis (LI; TG1 deletion), epidermolytic hyperkeratoses (EHK;K1 or 10 mutation), ichethyosis bullosa of Siemens (IBS; K2e mutation), palmo-plantar keratoderma (NSPPK; K1 mutation), ichthyosis, Keratoderma (NSPPK; K1 mutation), ichthyosis vulgaris (pro-filaggrin deficiency), Vohwinkle's disease (loricrin mutation), plus involucrin and K10 murine knockout animals. b) Assessing the mechanisms whereby CE-associated proteins influence permeability barrier function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FIBROGENIC FACTORS IN OCULAR CICATRICIAL PEMPHIGOID Principal Investigator & Institution: Ahmed, Razzaque A.; Associate Professor; Oral Medicine and Infection Immunity; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term objective of this grant application is to study the molecular mechanism of scarring in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP). Severe conjunctival scarring leads to blindness in about 25% of OCP patients, inspite of aggressive systemic therapy. The aim of this grant proposal is to identify some of the factors that are involved in the inflammatory and fibrotic stages, and define their role in the scarring process. Investigators studying ocular scarring in toxic epidermolysis necrosis, Steven-Johnson syndrome, epidermolysis bullosa acquisita, and other similar diseases will significantly benefit

Studies

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from these experiments. The PI has focused on only few molecules in an attempt to define a model system. Our preliminary studies suggest an important role for macrophage colony-stimulating factor (m-CSF), transforming growth factor (TGF)beta1, matrix metalloproteases (MMPs), and tissue inhibitors of metalloproteases (TIMPs) in regulating inflammatory and fibrotic events in the conjunctiva of OCP patients, and in fibroblasts isolated from conjunctiva of OCP patients. In our proposed study, we will determine the role of macrophage-recruiting molecules, isoforms of TGFbeta, connective tissue growth factor (CTFG), specific members of MMPs and TIMPs (as determined by our microarray analysis) in conjunctiva of patients with OCP. We will perform in vivo studies using an established mouse model of conjunctival scarring to determine the effects of blocking CTGF in this model. We anticipate that the results from studies proposed in this grant application will provide information that will identify and describe some of the key molecules that influence conjunctival scarring in patients with OCP. The studies have significant therapeutic potential. The identified molecules or portion of processes that mediate could be blocked or arrested, and this may result in cessation of disease progression and, prevention of blindness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC STUDIES OF MARGARITA ISLAND ECTODERMAL DYSPLASIA Principal Investigator & Institution: Spritz, Richard A.; Professor and Director; Human Medical Genetics Program; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from investigator's abstract): This is a proposal to carry out positional cloning of the gene for Margarita Island ectodermal dysplasia (ED4), a rare autosomal recessive disorder which is quite common (1/200) on Isla Margarita in the Caribbean, probably as result of a founder effect from one of the original Spanish settlers. The disease has been mapped by the applicant to a 1-2 Mb interval of chromosome 11q23, and shown to be associated with a common ancestral haplotype. A second aim of the proposal is to determine whether ED4 is allelic to the Zlotogora-Ogur syndrome, a rare disorder reported in three families with phenotypic similarity to ED4. After cloning the ED4 gene, the third aim of the proposal is to determine whether the murine ED4 homologue is responsible for the "rough-fur" murine mutation, making it a mouse model of the human disease. The last aim is to initiate studies to determine the function of the ED4 gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEMIDESMOSOMES IN BULLOUS PEMPHIGOID Principal Investigator & Institution: Giudice, George J.; Associate Professor; Dermatology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2004 Summary: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by the production of autoantibodies that react with components of the hemidesmosome, an adhesion-related organelle of basal epidermal keratinocytes. Studies supported by this grant utilized patient autoantibodies as specific probes to facilitate the molecular cloning and characterization of BP180, a major antigen associated with these autoimmune diseases. BP180 was shown to be a type II transmembrane protein with a long C-terminal collagenous domain that projects into the extracellular region beneath

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the epidermal hemidesmosome. The first specific aim of the current grant application addresses important questions regarding the structure of both the intracellular and extracellular domains of the BP180 protein. In the execution of these studies, high levels of recombinant forms of BP180 will be expressed in cultured mammalian cells using an Epstein Barr Virus-based vector, pCEP4. Using this system, the applicants recently demonstrated that the BP180 ectodomain is capable of forming a homotrimeric complex, with a molecular shape and flexibility properties consistent with their structural model of BP180 in which the ectodomain comprises a series of articulated, rigid rod-like structures. A part of this aim, they plan to define the protein segments that are essential for the assembly of the BP180 trimer, and to investigate the structural consequences of BP180 mutations that are known to be associated with inherited disorders of the basement membrane zone. Questions related to the function of BP180 will be addressed in specific aim 2. To further test their hypothesis that BP180 functions in cell-matrix attachment, they plan to extend their recent studies in which wild type BP180 was transfected into BP180-deficient keratinocytes from patients with generalized atrophic benign epidermolysis bullosa (GABEB). The GABEB keratinocytes and other cultured cells transfected with wild type and mutant BP180 expression constructs will be assayed for alterations in hemidesmosome assembly and/or cell matrix attachment properties. In addition, a variety of approaches will be employed to identify the extracellular BP180 ligand(s) and to determine whether ligand binding is coupled with the transduction of a signal across the membrane. In specific aim 3, the BP180 ectodomain will be further analyzed as the target of lgG and IgA class autoantibodies associated with several subepithelial blistering diseases such as cicatricial pemphigoid and linear IgA bullous dermatosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOPATHOGENESIS OF BULLOUS PEMPHIGOID Principal Investigator & Institution: Liu, Zhi; Dermatology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAY-2006 Summary: Bullous Pemphigoid (BP) and herpes gestationis (HG) are life-threatening blistering diseases that are characterized by the production of autoantibodies directed against the hemidesmosomal proteins, BPl80 and BP230, and by itie formation of subepidermal vesicles. The overall goal of this project is to advance our understanding of the immunopathological mechanisms operating in these diseases. The major focus of the present proposal is to test the hypothesis that the destruction of the dermalepidermal junction is caused by proleolytic enzymes released from infiltrating inflammatory cells. Specific aims 1 and 2 are to further dissect the mechanism of recruitment and activation of neutrophils (i.e. the role of cell adhesion molecules and cell surface receptors) and investigate the possible role of eosinophils in subepidermal blistering. Passive transfer experiments with pathogenic anti-BP180 IgG will be performed on mice deficient in proinflammatory cytokines, neutrophil migrationrelated integrins or activation-related Fc receptors. The role of eosinophils will be investigated by depletion and reconstitution experiments. Specific aim 3 is designed to determine the role of proteolytic enzymes and the reactive oxidants in experimental BP and HG and test the hypothesis that degradation products of BPl80 are chemotactic. Mice deficient in these proteinases will be injected with pathogenic IgG. The chemotactic activity of the BPl80 fragments will be tested by in vitro and in vivo chemotaxis assays. Specific aim 4 is to study effects and mechanisms of action of anti-inflammatory drugs in subepidermal blistering using passive transfer experiments and pharmacologic

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approaches. Specific aim 5 is to develop a novel system to directly test the pathogenic activity of autoantibodies from BP and HG patients' sera. These autoantibodies will be injected into neonatal transgenic mice expressing human BPl80 in the basal keratinocytes. Affinity-purified autoantibodies against specific antigenic sites on human BPl80 will also be used in this in viva system to map the pathogenic epitopes). The results from these studies will have profound clinical implications in the care of patients with BP and HG and other related diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CUTANEOUS DRUG REACTIONS Principal Investigator & Institution: Svensson, Craig K.; Professor and Division Head; Pharmaceutical Sciences; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Cutaneous drug reactions (CDR) are among the most frequent adverse medical events. Recent studies suggest that between 30 and 45 percent of all adverse drug reactions involve the skin. Of particular interest are the delayed-type hypersensitivity reactions that occur with sulfonamides and sulfones. While most investigators have focused on the role of differences in hepatic bioactivation and detoxification in determining predisposition to these reactions, it is uncertain and perhaps unlikely that liver-generated reactive metabolites would survive transit to the skin. We have developed a novel hypothesis wherein metabolic activation of drugs in keratinocytes provokes the release of signals that result in the activation of cutaneous dendritic cells, thereby initiating the cascade of events resulting in the manifestations of a CDR. The long term-goal of our project is to elucidate the mechanism of CDR and develop means to predict and/or prevent their occurence. The objective of the present proposal is to test the validity of our hypothesis using sulfamethoxazole (SMX) and dapsone, which are among the most frequent CDR-inducing drugs, as model compounds. The Specific Aims of this project are to determine: 1) If cyclooxygenase is the enzyme that bioactivates SMX and dapsone in normal human epidermal keratinocytes (NHEK). Preliminary studies have indicated that these compounds can be bioactivated by cyclooxygenase-2. We will identify the enzyme responsible for this bioactivation in NHEK using selective inhibitors and inducers, as well as recombinant enzyme. 2) If cytokines alter the bioactivation or detoxification of SMX and dapsone in NHEK. An inflammatory response has been shown to alter enzymes important in drug bioactivation, an event that appears to be mediated by cytokines. Cytokines may also alter the glutathione content of cells, an alteration that may alter the susceptibility of cells to these hydroxylamine metabolites. We will assess the effects of proinflammatory cytokines on the bioactivation/detoxication of SMX and dapsone in NHEK. 3) If NHEK incubated with hydroxylamine metabolites of SMX and dapsone release signals resulting in the activation of dendritic cells. After determining the mechanism of cell death induced by these metabolites, we will test the hypthothesis that they activate dendritic cells, either directly or indirectly (i.e., via signals released from NHEK). We anticipate that the results of the proposed studies will identify key points of intervention that will permit the prevention or management of these reactions. Moreover, they should enable us to develop in vitro screening tests that will permit the pre-clinical identification of drugs likely to pose a significant risk for the development of such reactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR GENETICS OF THE KERATODERMAS Principal Investigator & Institution: Christiano, Angela M.; Associate Professor; Dermatology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-JUL-1998; Project End 21-MAR-2004 Summary: (Adapted from the applicant's abstract)-This is a resubmission of a grant application proposing to search extensively for mutations that interfere with the normal process of epidermal and in particular palmoplantar keratinization. The project consists of three integrated and interdependent aims. The first one is to search for mutations in eleven candidate genes in a small number of families with a characterized inherited keratoderma. Specifically, the genes are loricrin, involucrin, envoplakin, desmoplakin, plakoglobin, desmogleins 1, 2, 3, desmocollins 1, 2 and 3, and the diseases include Netherton's, Mal-de-Maleda, Vohlwinkel's, Kindler/Weary, erythrokeratoderma, nonepidermolytic PPK, PRP, and eight others for which 1 to 10 families have been enlisted into studies. The second is to identify the mutated genes in large pedigrees with well-characterized, dominant, and fully penetrant keartodermas, one with EB superficialis, the other "Novel Acantholytic Disease." The pedigrees are so large that if the mutations do not map in the region of candidate genes, the first look, random polymorphisms will be used to saturate the map and localize the mutations. The third is to isolate and characterize genes that play a role in epidermal differentiation. Some of these have been cloned at the cDNA level, but the genomic organization, i.e., intronexon boundaries, is unknown. Others will be obtained from the results of the Specific Aim 2, namely, genes identified as mutated in EB superficialis, and the Novel Acantholytic Disease will be cloned and characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUCOUS PATHOGENESIS

MEMBRANE

PEMPHIGOID:

ORGAN

SPECIFIC

Principal Investigator & Institution: Bhol, Kailash C.; Orak Medicine Infection and Immunity; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant) The objective of this translational research grant application is to study a rare, and interesting potentially catastrophic, blistering autoimmune disease, which predominantly affects the mucous membranes known as mucous membrane pemphigoid (MMP). When it affects the oral cavity, eating and swallowing are exquisitely painful. Ocular involvement can frequently result in blindness. Since laryngeal disease can cause sudden asphyxiation and death, it mandates elective tracheostomy. Recently we described that, the anti-basement membrane zone (BMZ) antibodies found in the sera of MMP patients targets the cytoplasmic domain of human beta4 integrin. The clinical profile of mucosal involvement in MMP is variable, though the target antigen is present in all mucosae and skin. The investigator proposes to study the role of local factors involved in MMP. Using sera of patients with MMP, the investigator will identify binding of anti-BMZ antibodies to the basement membrane of the eye, nose, oral cavity, pharynx, esophagus, vagina and skin. Matching of clinical profiles with ability of patient's sera to bind to the BMZ of different mucosal tissues, or to different epitopes in the cytoplasmic domain of beta4 integrin will provide essential differences between systemic and local factors or the tissue microenvironments. The ability of sera from patients with MMP, and rabbit antibodies to bind to specific epitopes within the beta4 integrin, to produce sub-mucosal

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blisters in organ culture, using skin and different mucosal tissues, will be studied. Data from this study will provide important insights into how and why specific organs are involved, in a disease in which the autoantibody has the potential to cause disease in all tissues that contain the target antigen. Such advances can facilitate planning of future studies that focus on specific factors that may individually or collectively, play an important role in different organs in producing clinical disease, and this elucidate specific sites of pathology. The ability of the autoantibody to bind to specific tissues yet not produce clinical disease, might help understand and detect factors that can locally prevent disease manifestation and involvement. Such information can help generate site-specific therapy for purpose of clinical resolution and prevention of involvement. Thus MMP has the potential to be a model that could be applied to study many other multi systemic autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTI STEP TUMORIGENESIS, CONTROL OF CELL CYCLE ENTRY Principal Investigator & Institution: Land, Hartmut; Professor and Chair; Biomedical Genetics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: Carcinogenesis is caused by multiple co-operating genetic lesions leading to a progressive deregulation of cellular signaling and cell cycle restriction point control. The mutations involved result in oncogene activation or loss of tumor-suppressor gene function. However, the mechanisms by which these mutant genes co-operate in malignant cell transformation are largely unknown. Our laboratory has shown that the co-operation of oncogenic lesions involves integration of multiple signals converging on the regulation of cell cycle-dependent kinase complexes. Here we propose to investigate the molecular mechanisms by which the c-myc oncogene co-operates with activated Ras/Raf signaling. The c-myc oncogene is frequently activated in human cancer and is a potent inducer of proliferation and apoptosis. One essential step in Myc-induced proliferation is the activation of Cyclin E-dependent kinase (Cyclin E/Cdk2). Using genetic and biochemical approaches in tissue culture, we recently made the surprising finding that activation of cyclin E/Cdk2 by c-myc requires the ability of D cyclins to sequester Gl cell cycle inhibitors p27Kip1 and p21Cip1 (Ckis). We now propose to investigate whether the capability of D cyclins to sequester Ckis plays an important role in the induction of cell division by activated c-myc in an intact organism. Moreover, we plan to tea the hypothesis that sequestration of Ckis by D cyclins may play a significant role in organ development and during multi-step carcinogenesis. This work will provide insight into developing signaling pathway-based strategies for cancer therapy in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUTATION ANALYSIS IN EPIDEMOLYSIS BULLOSA Principal Investigator & Institution: Uitto, Jouni J.; Professor and Chair; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The central goal of this project is to define, at the level of nucleotide sequences of the genes, the mutations that cause various forms of epidermolysis bullosa (EB) and other disorders affecting the epidermis. The emphasis on this project in the past four years has been on elucidation of mutations in the wellestablished forms of EB, viz. the classic dystrophic (DEB) and junctional forms (JEB).

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During this past project period, since 1996, we have analyzed a total of 368 families with different forms of EB; for mutations in the candidate genes. As a result of these efforts, we have been able to identify 136 distinct mutations in the We VII collagen gene (CQL7A 0 in families with various forms of DEB, and examination of the mutation database has allowed us to develop genotype/phenotype correlations with prognostic implications (see the Progress Report below). Similarly, we have examined a total of 132 families with different forms of JEB, and we have been able to identify 118 distinctmutations in six different genes underlying different variants of JEB, these include LAMA3, LAMB3, LAMC2, ITGB4, ITGA6, and BPAG2/COL17Al. Within each JEB subtype, there is considerable phenotypic variability, and careful examination of the mutation database has allowed us to identify certain genotype/phenotype correlations. Thus, collectively, there has been a tremendous progress in elucidating the underlying molecular basis of different forms of EB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEMPHIGUS AND PEMPHIGOID Principal Investigator & Institution: Diaz, Luis A.; Professor and Chairman; Dermatology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 28-FEB-2006 Summary: This application represents the competitive continuation of the Merit Award R37-AR32081 that is funded until June 20, 2000. During the last 10 years of funding we have completed several relevant studies on pemphigus vulgaris (PV), non-endemic pemphigus foliaceus (PF), endemic PF [also known as Fogo Selvagem (FS)] and Bullous Pemphigoid (BP) that are summarized as follows: a) we have developed animals models of PV , PF, and FS by passive transfer of patients' IgG, b) we have developed affinitychromatography procedures to purify autoantibodies from PF, PV, and BP sera, c) we have developed a highly sensitive and specific ELISA to detect PF, PV, and BP autoantibodies using recombinant proteins, d) we have characterized a human settlement with a high prevalence of endemic FS (3 percent) in a Brazilian Indian Reservation, e) we have studied in this reservation 5 FS cases in the pre-clinical stage and several normal controls that exhibit moderate titers of anti-dsg1 IgG autoantibodies, predominantly IgG1. These autoantibodies increased several fold when FS was fully established, and the predominant IgG isotype was IgG4, f) we have been able to clone antigen-specific T cells from peripheral blood of FS patients from this Indian reservation. In addition, g) we mapped the hemidesmosome as the target of BP autoantibodies, h) we discovered and characterized the BP180 antigen as a component of hemidesmosomes, i) we developed the first animal model of BP by passive transfer of anti-BP antibodies. In this grant we hypothesize that in FS anti-dsg1 autoantibodies of the IgG1 and IgG4 subclass may differ in their pathogenicity and epitope-specificity. To test this hypothesis we will isolate and study dsg1-specific IgG1 and IgG4 from FS sera, clone and sequence V genes from B cells of these patients by single cell RT-PCR, develop monoclonal anti-idiotypic antibodies, generate recombinant anti-dsg1 Fabs, and carry out dsg1 epitope mapping studies. Similar studies will be performed with anti-dsg3 autoantibodies in PV. These studies may lead to new therapies for these serious cutaneous autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOLOGY AND PHASE II STUDIES OF TOPICAL AGENTS FOR SKIN CANCER PREVENTION Principal Investigator & Institution: Alberts, David S.; Professor of Medicine and Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: The overall goal of this Program Project is to develop safe and highly efficacious intervention strategies for prevention of melanoma nd nonmelanoma skin cancers (NMSC) and to develop basic science and clinical research approaches which will serve as models for the chemoprevention of a wide range of human epithelial cancers. In this Project, we propose to demonstrate that specific histopathologic and morphometric abnormalities, genetic alterations, and immunohistochemical surrogate endpoint biomarker (SEB) changes are associated with a multi-step progression from normal skin to NMSC or melanoma in human study participants and that these biomarkers can be modulated safely by novel topical chemoprevention agents. Approximately 60% of squamous cell carcinomas arise from pre- existing actinic keratoses (AKs) and /or under contiguous skin surfaces. AKs may represent a significant risk factor for melanoma as well. Additionally, case-control studies found that dysplastic nevi (DN) are the strongest risk factor for melanoma. In the first year of this grant, subjects with DN, SCC, AKs, and pre-clinical AKs will be recruited to document that specific histopathologic and morphometric abnormalities, genetic alterations and immunohistochemical biomarkers are associated with the progression from normal skin to AK to SCC and normal skin to DN to melanoma and that these biomarkers are reproducible for at least a three month time period. Researchers agree that the probability of successfully altering the natural history of any cancer increases by targeting an earlier, rather than a later, time point in carcinogenesis. Therefore, in years 2-5, subjects with preclinical AKs or DN will be recruited to conduct phase IIa randomized placebo-controlled cancer prevention clinical trials of topical agents including difluoromethylornithine (DFMO), epigallocatechin gallate (EGCG), 9-cisretinoic acid perillyl alcohol and sodium salicylate. Agents selected must first be shown: 1) active in a mouse UVB carcinogenesis model and/or a transgenic mouse melanoma model; 2) locally and systematically non-toxic in murine models; and 3) able to penetrate full thickness skin from BALB/c mice and humans (i.e. face lift skin). During these clinical studies we will determine the predictive accuracy of ultraviolet and polarized photography with respect to identification of abnormal histopathologic and morphometric areas of forearm skin epidermis and, ultimately, examine the histopathologic/morphometric and molecular genetic pathogenesis of skin preneoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION AND FUNCTION OF KERATINS IN THE EPIDERMIS Principal Investigator & Institution: Roop, Dennis; Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-MAR-2004 Summary: With the discovery that mutations in fourteen different keratin genes can cause eight distinct disorders that exhibit epithelial fragility, comes the realization that the keratin filament network is crucial to the structural integrity of epithelial tissues exposed to mechanical stress. The identification of mutations causing these disorders has improved our understanding of keratin intermediate filament structure and function, particularly with regard to the highly conserved regions of the central rod

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domain. However, two central questions in keratin biology still remain: First, how are the individual keratin genes regulated during normal and abnormal development? To address this question, we have chosen to look at two related keratins that have widely different regulatory properties. These are keratins K1 and K6. K1 is one of the first markers of keratinocyte differentiation, with its expression initially detected in postmitotic basal cells. Moreover, defects in K1 have been identified as causative in the skin disease epidermolytic hyperkeratosis, EHK. There are at least five mouse K6 genes, and specific isoforms are differentially expressed in the outer root sheath of hair follicles and in other epithelia. Interfollicular expression of K6 only occurs when keratinocytes are stressed or perturbed, such as in wounding. Mutations in two human K6 genes have been detected in different forms of pachyonychia congenita. The functional significance of multiple K6 genes remains to be determined. To address this question, we have initiated knock out experiments and on the basis of data generated to date, we suggest that certain human K6 genes have not yet been identified, and are in fact candidates for mutations in other disorders. The second question concerns the roles of the keratin and C-terminal end domains. These sequences are distinctive for each keratin protein but are remarkably well conserved across species and presumably have functional significance. In vitro studies have suggested that these domains interact with desmosomes and/or the cell envelope, however these interactions have not been confirmed by in vivo models. Two transgenic approaches are proposed to determine the functional role of the end domains in vivo. Finally, dominant skin disorders which affect post-mitotic epidermal cells present a difficult challenge for gene therapy. We propose to develop a mouse model for one of these disorders, EHK, and use it to assess gene therapy approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SMOKELESS TOBACCO USE AND CESSATION IN RURAL APPALACHIA Principal Investigator & Institution: Wewers, Mary Ellen.; Professor; None; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 30-JUN-2004 Summary: (provided by applicant): It is well documented that smokeless tobacco use is a major risk factor for a variety of oral pathoses such as gingival recession, leukoplakia and cancers of the mouth and pharynx. Rural Appalachians are at risk for tobaccorelated diseases and very little is known about their smokeless tobacco use characteristics, especially as these variables relate to oral health status. The purpose of this NIDCR Clinical Trial Pilot Grant are to compare the oral health status of rural adult Appalachian smokeless tobacco users and never-users, characterize smokeless tobacco consumption patterns, and refine a scientifically-valid AHRQ cessation intervention for use with smokeless tobacco users. Oral health indicators that determine the success of the intervention will be developed and tested. The intervention combines existing local agencies, such as a County Nurse and a County Extension Agent, with a lay facilitation model, and may represent an effective mechanism for reaching rural populations. Two rural Appalachian counties in the State of Ohio will participate in this study. One county will be assigned to an intervention, while the other will serve as the control county. Eligible adult smokeless tobacco users in both counties will be assessed for oral health status and smokeless tobacco use characteristics. Intervention county residents will receive a locally-based cessation intervention that will be managed by the County Nurse in the intervention county and delivered by trained lay educators. The County Extension Agent will be responsible for recruitment and retention efforts in this project.

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At end-of-treatment, and 6 and 12 months, participants from the intervention and control counties will be reassessed for tobacco use, using self-report and biochemical confirmation by saliva cotinine analysis. Comparisons of quit rates will be performed by Chi-square statistical techniques to detect a treatment effect. Multivariate logistic regression analyses will be performed to describe a model of quitter versus continuing user. Oral health status will also be evaluated at 12 months post intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUNLIGHT RELATED STEPS IN HUMAN SKIN CANCER Principal Investigator & Institution: Brash, Douglas E.; Professor; Therapeutic Radiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 30-JUN-2003 Summary: The long-term aim of this project is to understand how sunlight causes skin cancer. Skin is a unique system for revealing early events in cancer because the lesions are observable, the carcinogen is known, and some cancers progress through defined stages. We initially focussed on UV-induced mutations. Now, we are focussing on UVinduced apoptosis and its role in preventing or accelerating sunlight-induced cancer. The working hypothesis is that a key step in developing skin precancers is loss of cellular proofreading. That is, abnormal cells no longer commit suicide. Our previous work generated a model at each of three levels: genes, cell populations, and pharmacologic agents. Genetic model: Apoptosis requires both an abnormality detector, which involves p53, and a cell cycle abnormality signal. Cell population model: A UVinduced p53 mutation renders a cell apoptosis-resistant. Additional UV allows the mutant cell to clonally expand at the expense of its normal neighbors, resulting in a precancer. Pharmacology model: Many drugs affect the abnormality detector or the abnormality signal. The altered apoptosis biases the competition between normal and mutant cell populations, so that these agents act as chemopreventives or tumor promoters. The research in this application uses cultured cells, mouse skin, and human skin to test individual points of these models: i) Does apoptosis- resistance enable a mutant cell to clonally expand to a precancerous lesion? ii) Do the different mutant p53 alleles found in human skin cancers and precancers have different phenotypes for apoptosis versus cell cycle arrest? iii) Do chemopreventive agents and tumor promoters act by influencing UV-induced cellular proofreading? iv) What genes influence UVinduced cellular proofreading? v) How does a DNA photoproduct signal cell cycle arrest or apoptosis? vi) Does p53- mediated clonal expansion clone out single mutant cells already present in sun-damaged skin? These studies could find that: sunlight acts as a tumor promoter by killing unmutated cells; chemoprevention is beneficial only before apoptosis-resistant cells appear; and the genomic location of a DNA photoproduct determines whether cell cycle arrest or apoptosis ensues. The questions addressed here are directly relevant to the health of an increasing number of individuals: skin cancers are now as frequent as all other cancers combined. More broadly, the mechanisms operating in keratinocytes are likely to be a part of cancer development in other cell types as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis. by D'Armiento J, DiColandrea T, Dalal SS, Okada Y, Huang MT, Conney AH, Chada K.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230824

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Transgenic Mice Expressing a Mutant Keratin 10 Gene Reveal the Likely Genetic Basis for Epidermolytic Hyperkeratosis. by Fuchs E, Esteves RA, Coulombe PA.; 1992 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49613

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

3 4

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

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

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A case of cutaneous ganglioneuroma developing within a lesion of seborrheic keratosis. Author(s): Ohno S, Horiguchi Y, Shintaku M. Source: The Journal of Dermatology. 2002 May; 29(5): 300-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081162

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A case of seborrheic keratosis distributed along skin cleavage lines. Author(s): Li X, Zhu W. Source: The Journal of Dermatology. 1998 April; 25(4): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9609989

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A Korean case of keratosis follicularis squamosa (Dohi) successfully treated with roxithromycin. Author(s): Lee S, Kim SC. Source: The Journal of Dermatology. 2002 October; 29(10): 676-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433004

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A new family with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer. Author(s): Emmert S, Kuster W, Zutt M, Hanssle H, Hallermann C, Kretschmer L, Neumann C. Source: Journal of the American Academy of Dermatology. 2003 December; 49(6): 11669. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639410

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A patient with a seborrheic keratosis which caused impaired hearing by closure of the external auditory meatus. Author(s): Kobayashi M, Hiruma M, Suga Y, Nishimura K, Ogawa H. Source: International Journal of Dermatology. 2000 July; 39(7): 550-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10940123

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A poroid neoplasia arising close to a seborrheic keratosis and a trichoepithelioma. Author(s): Nagore E, Diaz F, Sanchez-Motilla JM, Prats A, Garcia-Castell J, Aliaga A. Source: The Journal of Dermatology. 1999 April; 26(4): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10343473

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A retrospective study of the effect of long-term topical application of retinaldehyde (0.05%) on the development of actinic keratosis. Author(s): Campanelli A, Naldi L. Source: Dermatology (Basel, Switzerland). 2002; 205(2): 146-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12218230

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A solitary cutaneous tumor with distinct areas of verruca and seborrheic keratosislike lesion. Author(s): Lazaris AC, Paraskevakou H, Davaris PS. Source: Pathology Oncology Research : Por. 1999; 5(4): 320-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10607930

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A survey of office visits for actinic keratosis as reported by NAMCS, 1990-1999. National Ambulatory Medical Care Survey. Author(s): Gupta AK, Cooper EA, Feldman SR, Fleischer AB Jr. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 August; 70(2 Suppl): 8-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353680

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Actinic keratosis is squamous cell carcinoma. Author(s): Lober BA, Lober CW. Source: Southern Medical Journal. 2000 July; 93(7): 650-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923948

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Actinic keratosis: a case of sun damage in the tropics. Author(s): Olasode OA, Onayemi O, Olasode BJ, Odeanmi WO. Source: Cent Afr J Med. 1997 June; 43(6): 177-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9431747

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Actinic keratosis: time to call a spade a spade. Author(s): Evans C, Cockerell CJ. Source: Southern Medical Journal. 2000 July; 93(7): 734-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923970

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Actinic keratosis--a histoenzymological study. Author(s): Taranu T, Caruntu ID, Taranu T, Petreus T. Source: Rev Med Chir Soc Med Nat Iasi. 2001 July-September; 105(3): 514-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12092184

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Alterations of p53 gene and Ha-ras gene are independent events in solar keratosis and squamous cell carcinoma. Author(s): Taguchi M, Tsuchida T, Ikeda S, Sekiya T. Source: Pathology International. 1998 September; 48(9): 689-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9778107

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An actinic keratosis is neither malignant nor premalignant: it is an initiated tumor. Author(s): Person JR. Source: Journal of the American Academy of Dermatology. 2003 April; 48(4): 637-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12664040

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Anti-tumor effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in seborrheic keratosis. Author(s): Asagami C, Muto M, Hirota T, Shimizu T, Hamamoto Y. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 1996 April; 1(1): 94-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9627701

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Apocrine acrosyringeal keratosis in association with syringocystoadenoma papilliferum. Author(s): Kishimoto S, Wakabayashi S, Yamamoto M, Noda Y, Takenaka H, Yasuno H. Source: The British Journal of Dermatology. 2000 March; 142(3): 543-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10735969

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Apoptosis in the areas of squamous differentiation of irritated seborrheic keratosis. Author(s): Pesce C, Scalora S. Source: Journal of Cutaneous Pathology. 2000 March; 27(3): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728813

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Arsenic keratosis and pigmentation accompanied by multiple Bowen's disease and genitourinary cancer in a psoriasis patient. Author(s): Park JY, Rim JH, Choe YB, Youn JI. Source: The Journal of Dermatology. 2002 July; 29(7): 446-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184646

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Arsenic-related Bowen's disease, palmar keratosis, and skin cancer. Author(s): Col M, Col C, Soran A, Sayli BS, Ozturk S. Source: Environmental Health Perspectives. 1999 August; 107(8): 687-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417369

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Basal cell carcinoma in seborrheic keratosis. Author(s): Mikhail GR, Mehregan AH. Source: Journal of the American Academy of Dermatology. 1982 April; 6(4 Pt 1): 500-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7076904

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Basal cell carcinoma with tricholemmal (at the lower portion) differentiation within seborrheic keratosis. Author(s): Misago N, Satoh T, Narisawa Y. Source: Journal of Cutaneous Pathology. 2003 March; 30(3): 196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641780

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Basal cell carcinoma within a seborrhoeic keratosis. Author(s): Andersen J. Source: Acta Pathol Microbiol Scand [a]. 1970; 78(2): 205-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4246750

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B-cell lymphoma after cyclosporine for keratosis lichenoides chronica. Author(s): Masouye I, Salomon D, Saurat JH. Source: Archives of Dermatology. 1993 July; 129(7): 914-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8323324

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Benign keratosis with a spectrum of follicular differentiation: a case series and investigation of a potential role of human papilloma virus. Author(s): Somach S, Morgan M. Source: Journal of Cutaneous Pathology. 2001 March; 28(3): 156-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168769

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Benign lichenoid keratosis due to constant pressure. Author(s): Ramesh V, Kulkarni SB, Misra RS. Source: The Australasian Journal of Dermatology. 1998 August; 39(3): 177-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9737046

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Benign lichenoid keratosis. Author(s): Frigy AF, Cooper PH. Source: American Journal of Clinical Pathology. 1985 April; 83(4): 439-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3984937

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Benign lichenoid keratosis. Author(s): Goette DK. Source: Archives of Dermatology. 1980 July; 116(7): 780-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7396541

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Benign lymphangioendothelioma manifested clinically as actinic keratosis. Author(s): Yiannias JA, Winkelmann RK. Source: Cutis; Cutaneous Medicine for the Practitioner. 2001 January; 67(1): 29-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204600

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Benign pigmented tumor with combined features of seborrheic keratosis and compound nevus. Author(s): Wagner RF Jr. Source: Cutis; Cutaneous Medicine for the Practitioner. 1991 December; 48(6): 463-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1836990

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Ber-EP4-positive phenotype differentiates actinic keratosis from superficial basal cell carcinoma. Author(s): Tope WD, Nowfar-Rad M, Kist DA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 May; 26(5): 415-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10816226

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Bowen's disease and senile keratosis arising. Author(s): Sobel HJ. Source: Arch Pathol. 1972 October; 94(4): 372. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5056933

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Carcinoma with eccrine differentiation arising in a seborrhoeic keratosis. Author(s): Miracco C, Angeloni G, Miracco F, Pirtoli L. Source: The British Journal of Dermatology. 2003 April; 148(4): 831-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752157

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Case #6. Smokeless tobacco keratosis. Author(s): Haring JI. Source: Rdh. 1993 June; 13(6): 10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8234877

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Case 10. Actinic keratosis. Author(s): Haring JI. Source: Rdh. 1998 October; 18(10): 16, 74. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10825914

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Cicatricial alopecia and keratosis pilaris. Keratosis follicularis spinulosa decalvans. Author(s): Romine KA, Rothschild JG, Hansen RC. Source: Archives of Dermatology. 1997 March; 133(3): 381, 384. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9080901

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Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis. Author(s): Persaud AN, Shamuelova E, Sherer D, Lou W, Singer G, Cervera C, Lamba S, Lebwohl MG. Source: Journal of the American Academy of Dermatology. 2002 October; 47(4): 553-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12271300

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Clinical findings, cutaneous pathology, and response to therapy in 21 patients with keratosis pilaris atrophicans. Author(s): Baden HP, Byers HR. Source: Archives of Dermatology. 1994 April; 130(4): 469-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8166484

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Clinical misdiagnosis of melanoma as well as squamous cell carcinoma masquerading as seborrheic keratosis. Author(s): Field LM. Source: J Dermatol Surg Oncol. 1994 March; 20(3): 222. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8151040

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Clinical misdiagnosis of squamous cell carcinoma in situ as seborrheic keratosis. A prospective study. Author(s): Sloan JB, Jaworsky C. Source: J Dermatol Surg Oncol. 1993 May; 19(5): 413-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8496484

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Clonal nature of seborrheic keratosis demonstrated by using the polymorphism of the human androgen receptor locus as a marker. Author(s): Nakamura H, Hirota S, Adachi S, Ozaki K, Asada H, Kitamura Y. Source: The Journal of Investigative Dermatology. 2001 April; 116(4): 506-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11286615

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Coexistence of subepidermal calcified nodule and keratosis punctata in a patient with hyperhidrosis. Author(s): Yamamoto T, Katayama I, Nishioka K. Source: The Journal of Dermatology. 1995 June; 22(6): 458-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7650247

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Cole disease: hypopigmentation with punctate keratosis of the palms and soles. Author(s): Vignale R, Yusin A, Panuncio A, Abulafia J, Reyno Z, Vaglio A. Source: Pediatric Dermatology. 2002 July-August; 19(4): 302-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220272

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Comorbidity of keratosis follicularis (Darier's Disease) and bipolar affective disorder: an indication for valproate instead of lithium. Author(s): Ehrt U, Brieger P. Source: General Hospital Psychiatry. 2000 March-April; 22(2): 128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10896494

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Comparative histochemical study of Bowen's disease and actinic keratosis: preserved normal basal cells in Bowen's disease. Author(s): Ishida H, Kumakiri M, Ueda K, Lao LM, Yanagihara M, Asamoto K, Imamura Y, Noriki S, Fukuda M. Source: Eur J Histochem. 2001; 45(2): 177-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11512639

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Compare your diagnosis. Xanthogranuloma, seborrheic keratosis associated with mycosis fungoides, Kikuchi's disease. Author(s): Ackerman AB, Kerl H, LeBoit PE. Source: The American Journal of Dermatopathology. 1999 February; 21(1): 79-81, 94-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10027533

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Comparison of the clinical and histological effects of 5-fluorouracil (5-FU) alone and of 5-FU preceded by dimethyl-sulphoxide (DMSO) on senile keratosis. Author(s): Garcia-Perez A, Aparicio M, Carapeto FJ. Source: Dermatologica. 1970; 140: Suppl 1: 119+. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5471357

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Comparison of the microvasculature of basal cell carcinoma and actinic keratosis using intravital microscopy and immunohistochemistry. Author(s): Newell B, Bedlow AJ, Cliff S, Drysdale SB, Stanton AW, Mortimer PS. Source: The British Journal of Dermatology. 2003 July; 149(1): 105-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890202

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Confirmation of X-linked inheritance and provisional mapping of the keratosis follicularis spinulosa decalvans gene on Xp in a large Dutch family. Author(s): Oosterwijk JC, Nelen M, Van Zandvoort PM, Van Osch LD, Oranje AP, Wittebol-Post D, Van Oost BA. Source: Ophthalmic Paediatr Genet. 1992 March; 13(1): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1350668

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Congenital trichoid keratosis of the scalp. Author(s): Timpatanapong P, Jerasutus S, Sriprachya-anunt S, Hotrakitya S. Source: Archives of Dermatology. 1992 November; 128(11): 1549-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1444515

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Conservative clinical diagnoses in seborrheic keratosis. Author(s): Bryant J. Source: Archives of Dermatology. 1998 June; 134(6): 752-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9645652

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Cyclin D and retinoblastoma gene product expression in actinic keratosis and cutaneous squamous cell carcinoma in relation to p53 expression. Author(s): Bito T, Ueda M, Ahmed NU, Nagano T, Ichihashi M. Source: Journal of Cutaneous Pathology. 1995 October; 22(5): 427-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8594075

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Delayed wound healing after three different treatments for widespread actinic keratosis on the atrophic bald scalp. Author(s): Quaedvlieg PJ, Ostertag JU, Krekels GA, Neumann HA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 October; 29(10): 1052-6; Discussion 1056. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974704

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Demonstration of antibody to 230 kDa bullous pemphigoid antigen in lichen planuslike keratosis. Author(s): Seishima M, Izumi T, Kanoh H, Kitajima Y. Source: European Journal of Dermatology : Ejd. 1999 July-August; 9(5): 393-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417446

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Dermacase. Keratosis follicularis (Darier's disease). Author(s): Enta T. Source: Can Fam Physician. 1997 November; 43: 1929, 1937. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9386878

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Dermacase. Keratosis piloris. Author(s): Enta T, Adams SP. Source: Can Fam Physician. 1999 August; 45: 1871, 1880. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463085

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Dermacase. Seborrheic keratosis. Author(s): Enta T. Source: Can Fam Physician. 1993 February; 39: 250, 460. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8495115

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Dermacase. Seborrheic keratosis. Author(s): Enta T. Source: Can Fam Physician. 1994 August; 40: 1401, 1406. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8081119

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Dermatitis herpetiformis Duhring with palmoplantar keratosis. Author(s): Ohshima Y, Tamada Y, Matsumoto Y, Hashimoto T. Source: The British Journal of Dermatology. 2003 December; 149(6): 1300-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674919

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Dermoscopic diagnosis of seborrheic keratosis. Author(s): Braun RP, Rabinovitz H, Oliviero M, Kopf AW, Saurat JH. Source: Clinics in Dermatology. 2002 May-June; 20(3): 270-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074865

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Dermoscopy of pigmented seborrheic keratosis: a morphological study. Author(s): Braun RP, Rabinovitz HS, Krischer J, Kreusch J, Oliviero M, Naldi L, Kopf AW, Saurat JH. Source: Archives of Dermatology. 2002 December; 138(12): 1556-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472342

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Desmoplastic seborrheic keratosis. Author(s): King R, Page RN, Googe PB. Source: The American Journal of Dermatopathology. 2003 June; 25(3): 210-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775983

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Detection and sequences of human papillomavirus DNA in nongenital seborrhoeic keratosis of immunopotent individuals. Author(s): Gushi A, Kanekura T, Kanzaki T, Eizuru Y. Source: Journal of Dermatological Science. 2003 April; 31(2): 143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670725

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Detection of human papillomavirus and response to topical 5% imiquimod in a case of stucco keratosis. Author(s): Stockfleth E, Rowert J, Arndt R, Christophers E, Meyer T. Source: The British Journal of Dermatology. 2000 October; 143(4): 846-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11069470

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Detection of human papillomavirus DNA in seborrheic keratosis by polymerase chain reaction. Author(s): Zhu WY, Leonardi C, Penneys NS. Source: Journal of Dermatological Science. 1992 November; 4(3): 166-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1337468

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Diagnostic value of DNA content in keratosis and adult papilloma of the larynx. Author(s): Mangoud AM, Abdel-Wahab RM, Rasmy E. Source: J Egypt Soc Parasitol. 1991 December; 21(3): 823-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1765696

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Differential expression of proliferation- and apoptosis-related markers in lentigo maligna and solar keratosis keratinocytes. Author(s): Feinmesser M, Tsabari C, Fichman S, Hodak E, Sulkes J, Okon E. Source: The American Journal of Dermatopathology. 2003 August; 25(4): 300-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12876487

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Differentiation disorders of keratinocytes in seborrheic keratosis (acanthotic type). Author(s): Fujisawa H, Naito Y, Muraki R, Baba T. Source: The Journal of Dermatology. 1991 November; 18(11): 635-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1724777

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Distal oblique osteotomy for intractable plantar keratosis of the middle three metatarsals. Author(s): Pedowitz WJ. Source: Foot Ankle. 1988 August; 9(1): 7-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2975626

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DNA repair synthesis in fibroblast strains from patients with actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or malignant melanoma after treatment with ultraviolet light, N-acetoxy-2-acetyl-aminofluorene, methyl methanesulfonate, and N-methyl-N-nitrosourea. Author(s): Thielmann HW, Edler L, Burkhardt MR, Jung EG. Source: Journal of Cancer Research and Clinical Oncology. 1987; 113(2): 171-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3558453

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Documented evolution of a solar lentigo into a solitary lichen planus-like keratosis. Author(s): Goldenhersh MA, Barnhill RL, Rosenbaum HM, Stenn KS. Source: Journal of Cutaneous Pathology. 1986 August; 13(4): 308-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3771875

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Dominant dystrophic epidermolysis bullosa with keratosis punctata. Author(s): Puig L, Moreno A, Noguera X, de Moragas JM. Source: Journal of the American Academy of Dermatology. 1986 December; 15(6): 128991. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2948976

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Eccrine porocarcinoma arising in a seborrheic keratosis evaluated with dermoscopy and treated with Mohs' technique. Author(s): Johr R, Saghari S, Nouri K. Source: International Journal of Dermatology. 2003 August; 42(8): 653-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890117

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Effect of a low-fat diet on the incidence of actinic keratosis. Author(s): Black HS, Herd JA, Goldberg LH, Wolf JE Jr, Thornby JI, Rosen T, Bruce S, Tschen JA, Foreyt JP, Scott LW, et al. Source: The New England Journal of Medicine. 1994 May 5; 330(18): 1272-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8145782

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Effect of topical 5-fluorouracil treatment on actinic keratosis: a light and electron microscopic study. Author(s): Hodge SJ, Schrodt GR, Owen LG. Source: Journal of Cutaneous Pathology. 1974; 1(6): 238-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4470728

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Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. Author(s): Weiss J, Menter A, Hevia O, Jones T, Ling M, Rist T, Roberts J, Shavin JS, Sklar J, Webster G, Connolly M, Furst K, Levy S. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 August; 70(2 Suppl): 22-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353677

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Electron microscopic observations of arsenical keratosis and Bowen's disease associated with chronic arsenicism. Author(s): Ohyama K, Sonoda K, Kuwahara H. Source: Dermatologica. 1982 March; 164(3): 161-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7084538

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Enhanced expression of p16 in seborrhoeic keratosis; a lesion of accumulated senescent epidermal cells in G1 arrest. Author(s): Nakamura S, Nishioka K. Source: The British Journal of Dermatology. 2003 September; 149(3): 560-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510989

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Epidermolytic alterations in focal palmoplantar and gingival keratosis. Author(s): Kolde G, Bethke G, Reichart PA. Source: American Journal of Medical Genetics. 2001 December 15; 104(4): 339-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11754071

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Epidermolytic hyperkeratosis of the nails in keratosis palmoplantaris nummularis. Author(s): Tosti A, Fanti PA, Piraccini BM, Bardazzi F, Misciali C. Source: Acta Dermato-Venereologica. 1995 September; 75(5): 405-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8615066

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Epidermolytic variant of solar keratosis. Author(s): Ackerman AB, Reed RJ. Source: Archives of Dermatology. 1973 January; 107(1): 104-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4682532

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Epithelial migration in keratosis obturans. Author(s): Corbridge RJ, Michaels L, Wright T. Source: American Journal of Otolaryngology. 1996 November-December; 17(6): 411-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8944302

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Eruptive seborrhoeic keratosis in human immunodeficiency virus infection: a coincidence or 'the sign of Leser-Trelat'? Author(s): Inamadar AC, Palit A. Source: The British Journal of Dermatology. 2003 August; 149(2): 435-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932267

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Etretinate in treatment of actinic keratosis. A double-blind crossover study. Author(s): Moriarty M, Dunn J, Darragh A, Lambe R, Brick I. Source: Lancet. 1982 February 13; 1(8268): 364-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6120350

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Evaluation of 5-fluorouracil in the treatment of actinic keratosis of the lip. Author(s): Warnock GR, Fuller RP Jr, Pelleu GB Jr. Source: Oral Surg Oral Med Oral Pathol. 1981 November; 52(5): 501-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6946379

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Evaluation of proliferating cell nuclear antigen as a surrogate end point biomarker in actinic keratosis and adjacent, normal-appearing, and non-sun-exposed human skin samples. Author(s): Einspahr J, Alberts DS, Aickin M, Welch K, Bozzo P, Levine N, Grogan T. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1996 May; 5(5): 343-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9162299

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Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. Author(s): Loven K, Stein L, Furst K, Levy S. Source: Clinical Therapeutics. 2002 June; 24(6): 990-1000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117087

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Expression of matrix metalloproteinase-1, -2 and -3 in squamous cell carcinoma and actinic keratosis. Author(s): Tsukifuji R, Tagawa K, Hatamochi A, Shinkai H. Source: British Journal of Cancer. 1999 June; 80(7): 1087-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10362121

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Expression of p53 protein in actinic keratosis, adjacent, normal-appearing, and nonsun-exposed human skin. Author(s): Einspahr J, Alberts DS, Aickin M, Welch K, Bozzo P, Grogan T, Nelson M. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1997 August; 6(8): 583-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9264270

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Expression of p53, bcl-2 and growth hormone receptor in actinic keratosis, hypertrophic type. Author(s): Stanimirovic A, Cupic H, Bosnjak B, Kruslin B, Belicza M. Source: Archives of Dermatological Research. 2003 July; 295(3): 102-8. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756585

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Familial cosegregation of major affective disorder and Darier's disease (keratosis follicularis) Author(s): Craddock N, Owen M, Burge S, Kurian B, Thomas P, McGuffin P. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1994 March; 164(3): 355-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8199789

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Familial hereditary, progressive sensori-neural hearing loss with keratosis palmaris and plantaris. Author(s): Bititci OO. Source: The Journal of Laryngology and Otology. 1975 November; 89(11): 1143-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=127819

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Fasciotomy in the treatment of plantar keratosis and other conditions of the foot. Author(s): Miller WA. Source: J Okla State Med Assoc. 1973 January; 66(1): 13-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4687472

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Focal keratosis follicularis overlying dermatofibroma. Author(s): Ackerman AB, Hyman AB. Source: Archives of Dermatology. 1971 August; 104(2): 219. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5093176

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Focal keratosis follicularis overlying dermatofibroma. Author(s): Ackerman AB, Capland L, Rywlin AM. Source: The British Journal of Dermatology. 1971 February; 84(2): 167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5548467

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Follicular keratoses. Pilot studies of serum level of vitamin A and liver function tests during administration of retinoic acid in hyperkeratosis follicularis et parafollicularis (Kyrle's disease), pityriasis rubra pilaris, and keratosis follicularis (Darier's disease). Author(s): Gunther S, Alston W. Source: Dermatologica. 1973; 147(4): 274-83. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4780779

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Follicular keratosis in children. Author(s): Panja SK, Chatterjee SK, Mukherjee KL. Source: Indian J Dermatol. 1970 April; 15(3): 75-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5469707

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Follicular keratosis of the chin. Author(s): Brenner S, Brandsen R. Source: Journal of the American Academy of Dermatology. 1992 December; 27(6 Pt 1): 1032. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1479091

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Follicular keratosis of the chin. Author(s): Padilha-Goncalves A. Source: Journal of the American Academy of Dermatology. 1992 December; 27(6 Pt 1): 1032. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1301039

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Follicular keratosis of the chin. Author(s): Kanzaki T, Morita A, Takashima A. Source: Journal of the American Academy of Dermatology. 1992 January; 26(1): 134-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1732325

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Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma. Author(s): Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP. Source: International Journal of Dermatology. 1998 September; 37(9): 677-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9762818

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Frequency of seborrheic keratosis biopsies in the United States: a benchmark of skin lesion care quality and cost effectiveness. Author(s): Duque MI, Jordan JR, Fleischer AB Jr, Williford PM, Feldman SR, Teuschler H, Chen GJ. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 August; 29(8): 796-801; Discussion 801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859377

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From actinic keratosis to squamous cell carcinoma. Author(s): Ortonne JP. Source: The British Journal of Dermatology. 2002 April; 146 Suppl 61: 20-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966728

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From sunlight to actinic keratosis to squamous cell carcinoma. Author(s): Cohn BA. Source: Journal of the American Academy of Dermatology. 2000 January; 42(1 Pt 1): 1434. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10607337

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Gene dosage of the spermidine/spermine N(1)-acetyltransferase ( SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD). Author(s): Gimelli G, Giglio S, Zuffardi O, Alhonen L, Suppola S, Cusano R, Lo Nigro C, Gatti R, Ravazzolo R, Seri M. Source: Human Genetics. 2002 September; 111(3): 235-41. Epub 2002 August 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12215835

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Genetic linkage evaluation of twenty-four loci in an eastern Canadian family segregating Darier's disease (keratosis follicularis). Author(s): Sidenberg DG, Berg D, Bassett AS, King N, Petronis A, Kamble AB, Kennedy JL. Source: Journal of the American Academy of Dermatology. 1994 July; 31(1): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8021367

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Genetic linkage for Darier disease (keratosis follicularis). Author(s): Kennedy JL, Berg D, Bassett AS, Roy R, King N, Perkins M. Source: American Journal of Medical Genetics. 1995 January 30; 55(3): 307-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7537018

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Giant irritated seborrheic keratosis mimicking verrucous carcinoma. Author(s): Mochizuki T, Fujigaki T, Tanaka S, Hironaga M. Source: The Journal of Dermatology. 1985 August; 12(4): 341-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3910690

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Giant lobulated seborrheic keratosis at an unusual site. Author(s): Phiske M, Mamidwar S, Dhurat R, Jerajani HR, Randive N, Joshi M. Source: Indian J Pathol Microbiol. 2003 January; 46(1): 96-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027742

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Giant pedunculated seborrheic keratosis. Author(s): Baer RL. Source: Archives of Dermatology. 1979 May; 115(5): 627. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=443844

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Giant seborrheic keratosis on the frontal scalp treated with topical fluorouracil. Author(s): Tsuji T, Morita A. Source: The Journal of Dermatology. 1995 January; 22(1): 74-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7897031

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Gigantic metameric seborrheic keratosis. Author(s): Sugarman JL, McCalmont TH, Frieden IJ, Dover J, Arndt K. Source: Plastic and Reconstructive Surgery. 2003 April 15; 111(5): 1775-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655244

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Gigantic metameric seborrheic keratosis. Author(s): Hernandez-Perez E, Espinoza Figueroa D. Source: Plastic and Reconstructive Surgery. 2003 August; 112(2): 706; Author Reply 7067. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900651

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Gigantic methameric seborrheic keratosis. Author(s): Faga A, Rosso R, Buoro M, Valdatta L. Source: Plastic and Reconstructive Surgery. 2002 March; 109(3): 1198-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11884860

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Globulelike dermoscopic structures in pigmented seborrheic keratosis. Author(s): Provost N, Kopf AW, Rabinovitz HS, Oliviero MC, Toussaint S, Kamino HH. Source: Archives of Dermatology. 1997 April; 133(4): 540-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9126023

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Guess what! Keratosis lichenoides chronica. Author(s): Chikama R, Terui T, Tanita M, Tagami H. Source: European Journal of Dermatology : Ejd. 1999 June; 9(4): 319-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10465619

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Guess what! Solitary lichen planus-like benign keratosis. Author(s): Borgia F, Vaccaro M, D'Amico D, Guarneri C, Guarneri F, Cannavo S. Source: European Journal of Dermatology : Ejd. 2001 January-February; 11(1): 69-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11174145

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Guess what? Isolated palmoplantar hyperkeratosis revealing keratosis lichenoides chronica. Author(s): Thielulent N, Grezard P, Wolf F, Balme B, Perrot H. Source: European Journal of Dermatology : Ejd. 1999 September; 9(6): 497-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10610235

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Halo seborrheic keratosis associated with colon carcinoma. Author(s): Vignale R, Espasandin J, Deneo H, Gonzalez V. Source: International Journal of Dermatology. 1993 November; 32(11): 846. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8270353

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Halo seborrheic keratosis. Author(s): Migally M, Migally N. Source: International Journal of Dermatology. 1983 June; 22(5): 307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6874189

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Health economic evaluation of non-melanoma skin cancer and actinic keratosis. Author(s): Higashi MK, Veenstra DL, Langley PC. Source: Pharmacoeconomics. 2004; 22(2): 83-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14731050

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Hereditary keratosis. Author(s): Stiff RH, Ferraro E. Source: Oral Surg Oral Med Oral Pathol. 1969 November; 28(5): 697-701. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5259455

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Hereditary mucosal keratosis. Author(s): Verma BS. Source: Indian Journal of Medical Sciences. 1967 May; 21(5): 310-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6042731

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Hereditary palmoplantar keratosis of the Gamborg Nielsen type. Clinical and ultrastructural characteristics of a new type of autosomal recessive palmoplantar keratosis. Author(s): Kastl I, Anton-Lamprecht I, Gamborg Nielsen P. Source: Archives of Dermatological Research. 1990; 282(6): 363-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2260881

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High body mass index, dry scaly leg skin and atopic conditions are highly associated with keratosis pilaris. Author(s): Yosipovitch G, Mevorah B, Mashiach J, Chan YH, David M. Source: Dermatology (Basel, Switzerland). 2000; 201(1): 34-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971056

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Histopathology of incipient intraepidermal squamous cell carcinoma ("actinic keratosis"). Author(s): Cockerell CJ. Source: Journal of the American Academy of Dermatology. 2000 January; 42(1 Pt 2): 117. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10607351

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Human papillomavirus (HPV) infection in seborrheic keratosis. Author(s): Zhao YK, Lin YX, Luo RY, Huang XY, Liu MZ, Xia M, Jin H. Source: The American Journal of Dermatopathology. 1989 June; 11(3): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2543229

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Human papillomavirus and seborrheic keratosis. Author(s): Jacyk WK. Source: The American Journal of Dermatopathology. 1991 October; 13(5): 525-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1659247

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Human papillomavirus infection in actinic keratosis and bowen's disease: comparative study with expression of cell-cycle regulatory proteins p21(Waf1/Cip1), p53, PCNA, Ki-67, and Bcl-2 in positive and negative lesions. Author(s): Mitsuishi T, Kawana S, Kato T, Kawashima M. Source: Human Pathology. 2003 September; 34(9): 886-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562284

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Hyperplasia, keratosis, dysplasia and carcinoma in situ of the vocal cords--a followup study. Author(s): Hellquist H, Lundgren J, Olofsson J. Source: Clinical Otolaryngology and Allied Sciences. 1982 February; 7(1): 11-27. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7037233

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Hypertrophic actinic keratosis. Author(s): Billano RA, Little WP. Source: Journal of the American Academy of Dermatology. 1982 October; 7(4): 484-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7142459

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Hypopigmentation with punctate keratosis of the palms and soles. Author(s): Cole LA. Source: Archives of Dermatology. 1976 July; 112(7): 998-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=132904

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Hypotrichosis with keratosis pilaris: electrophoretical study of hair fibrous proteins from a patient. Author(s): Dekio S, Nagashima T, Watanabe Y, Jidoi J. Source: Dermatologica. 1989; 179(3): 118-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2591617

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Hystrix-like keratosis with nail and joint-involvement: a new genodermatosis? Author(s): Schulz-Kiesow M, Metze D, Traupe H. Source: Dermatology (Basel, Switzerland). 1996; 192(4): 321-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8864365

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Identification of the genetic locus for keratosis palmaris et plantaris on chromosome 17 near the RARA and keratin type I genes. Author(s): Rogaev EI, Rogaeva EA, Ginter EK, Korovaitseva GI, Farrer LA, Shlensky AB, Pritkov AN, Mordovtsev VN, St George-Hyslop PH. Source: Nature Genetics. 1993 October; 5(2): 158-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7504553

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Immunohistochemical examination of tumor-suppressor gene p53 product and pyrimidine dimer in solar keratosis. Author(s): Taguchi M, Watanabe S, Sato Y, Kameya T, Munakata N, Ishihara K, Nakane PK, Hisatome H, Ikeda S. Source: Journal of Cancer Research and Clinical Oncology. 1993; 119(5): 260-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7680043

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Immunohistochemical localization of keratins and involucrin in solar keratosis and Bowen's disease. Author(s): Ichikawa E, Watanabe S, Otsuka F. Source: The American Journal of Dermatopathology. 1995 April; 17(2): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8600780

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Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin. Author(s): Krunic AL, Garrod DR, Madani S, Buchanan MD, Clark RE. Source: British Journal of Cancer. 1998 April; 77(8): 1275-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579833

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Immunohistochemical study on keratin expression in certain cutaneous epithelial neoplasms. Basal cell carcinoma, pilomatricoma, and seborrheic keratosis. Author(s): Shimizu N, Ito M, Tazawa T, Sato Y. Source: The American Journal of Dermatopathology. 1989 December; 11(6): 534-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2481408

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Immunohistochemistry detects differences between lichen planus-like keratosis, lichen planus, and lichenoid actinic keratosis. Author(s): Prieto VG, Casal M, McNutt NS. Source: Journal of Cutaneous Pathology. 1993 April; 20(2): 143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8320359

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Immunophenotypic and viral (human papillomavirus) correlates of vulvar seborrheic keratosis. Author(s): Bai H, Cviko A, Granter S, Yuan L, Betensky RA, Crum CP. Source: Human Pathology. 2003 June; 34(6): 559-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827609

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Incidence of actinic keratosis of Japanese in Kasai City, Hyogo. Author(s): Suzuki T, Ueda M, Naruse K, Nagano T, Harada S, Imaizumi K, Watanabe S, Ichihashi M. Source: Journal of Dermatological Science. 1997 November; 16(1): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438911

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Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light in human skin maintained in severe combined immunodeficient mice. Author(s): Nomura T, Nakajima H, Hongyo T, Taniguchi E, Fukuda K, Li LY, Kurooka M, Sutoh K, Hande PM, Kawaguchi T, Ueda M, Takatera H. Source: Cancer Research. 1997 June 1; 57(11): 2081-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9187098

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Inflammation of actinic keratosis caused by systemic chemotherapy--2'deoxycoformycin. Author(s): Camisa C. Source: Journal of the American Academy of Dermatology. 1988 October; 19(4): 758. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3263402

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Infundibular keratosis--a prototype of benign infundibular tumours. Author(s): Ishida-Yamamoto A, Iizuka H. Source: Clinical and Experimental Dermatology. 1989 March; 14(2): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2598488

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Infundibular keratosis--report of two cases. Author(s): Keong CH, Maruyama R, Katsumata M. Source: The Journal of Dermatology. 1990 August; 17(8): 510-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2229657

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Internalization of gap junctions in benign familial pemphigus (Hailey-Hailey disease) and keratosis follicularis (Darier's disease). Author(s): Haftek M, Kowalewski C, Mesnil M, Blaszczyk M, Schmitt D. Source: The British Journal of Dermatology. 1999 August; 141(2): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468792

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Invasive cutaneous squamous cell carcinoma associated with actinic keratosis: a case with orbital invasion and meningeal infiltration. Author(s): Schwarze HP, Loche F, Gorguet MC, Kuchta J, Bazex J. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 July; 25(7): 587-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10469120

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Inverted follicular keratosis and papillomavirus infection. Author(s): Hori K. Source: The American Journal of Dermatopathology. 1991 April; 13(2): 145-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1851400

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Inverted follicular keratosis of the vulvar skin: a lesion that can be confused with squamous cell carcinoma. Author(s): Roth LM, Look KY. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 2000 October; 19(4): 369-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109167

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Inverted follicular keratosis. Author(s): Soylu L, Akcali C, Aydogan LB, Ozsahinoglu C, Tuncer I. Source: American Journal of Otolaryngology. 1993 July-August; 14(4): 247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8214316

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Inverted follicular keratosis. Author(s): Shih CC, Yu HS, Tung YC, Tsai KB, Cheng ST. Source: Kaohsiung J Med Sci. 2001 January; 17(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11411260

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In-vitro DNA synthesis of keratinocytes in normal human skin, psoriasis, seborrhoeic keratosis, Bowen's disease and basal cell carcinoma. Author(s): Morimoto Y, Saga K, Bando M, Takahashi M. Source: The British Journal of Dermatology. 1991 July; 125(1): 9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1831385

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Is imiquimod effective and safe for actinic keratosis? Author(s): Walker JK, Koenig C. Source: The Journal of Family Practice. 2003 March; 52(3): 184-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620165

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Keratosis follicularis spinulosa decalvans: confirmation of linkage to Xp22.13-p22.2. Author(s): Porteous ME, Strain L, Logie LJ, Herd RM, Benton EC. Source: Journal of Medical Genetics. 1998 April; 35(4): 336-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9598732

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Keratosis follicularis squamosa (Dohi): a follicular keratotic disorder well known in Japan. Author(s): Shimizu S, Shimizu T, Tateishi Y, Shimizu H. Source: The British Journal of Dermatology. 2001 May; 144(5): 1070-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359401

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Keratosis follicularis. Author(s): Kosann MK. Source: Dermatology Online Journal [electronic Resource]. 2003 October; 9(4): 35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594608

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Keratosis lichenoides chronica in childhood. Author(s): Redondo P, Solano T. Source: Clinical and Experimental Dermatology. 2002 June; 27(4): 283-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139671

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Keratosis lichenoides chronica mimicking verrucous secondary syphilis. Author(s): Jayaraman AG, Pomerantz D, Robinson-Bostom L. Source: Journal of the American Academy of Dermatology. 2003 September; 49(3): 511-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963920

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Keratosis lichenoides chronica. Author(s): Konstantinov KN, Sondergaard J, Izuno G, Obreshkova E. Source: Journal of the American Academy of Dermatology. 1998 February; 38(2 Pt 2): 306-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9486703

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Keratosis lichenoides chronica. Author(s): Taberner R, Puig L, Fernandez-Figueras T, Alomar A. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 January; 15(1): 84-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451338

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Keratosis lichenoides chronica: a variant of lichen planus. Author(s): Grunwald MH, Amichai B, Finkelstein E, Kachko L. Source: The Journal of Dermatology. 1997 October; 24(10): 630-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9375461

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Keratosis lichenoides chronica: characteristics and response to acitretin. Author(s): Avermaete A, Kreuter JA, Stucker M, Von Kobyletzki G, Altmeyer P, Jansen T. Source: The British Journal of Dermatology. 2001 February; 144(2): 422-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11251590

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Keratosis lichenoides chronica: marked response to calcipotriol ointment. Author(s): Chang SE, Jung EC, Hong SM, Choi JH, Sung KJ, Moon KC, Koh JK. Source: The Journal of Dermatology. 2000 February; 27(2): 123-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10721662

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Keratosis lichenoides chronica: report of a new case, with success of PUVA therapy. Author(s): Ghislain PD, De Beir A, Creusy C, Modiano P. Source: Dermatology Online Journal [electronic Resource]. 2001 February; 7(1): 4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328625

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Keratosis palmoplantaris varians of Wachters. Author(s): Paoli S, Mastrolorenzo A. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1999 January; 12(1): 33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10188147

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Keratosis pilaris and hereditary koilonychia without monilethrix. Author(s): Thai KE, Sinclair RD. Source: Journal of the American Academy of Dermatology. 2001 October; 45(4): 627-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11568761

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Keratosis pilaris and ulerythema ophryogenes associated with an 18p deletion caused by a Y/18 translocation. Author(s): Nazarenko SA, Ostroverkhova NV, Vasiljeva EO, Nazarenko LP, Puzyrev VP, Malet P, Nemtseva TA. Source: American Journal of Medical Genetics. 1999 July 16; 85(2): 179-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10406673

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Keratosis pilaris atrophicans in mother and daughter. Author(s): Khumalo NP, Loo WJ, Hollowood K, Salvary I, Graham RM, Dawber RP. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 July; 16(4): 397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224702

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Keratosis pilaris. Author(s): Ahlawat D. Source: Indian Pediatrics. 2002 December; 39(12): 1165-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522283

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Keratosis pilaris. Author(s): Lateef A, Schwartz RA. Source: Cutis; Cutaneous Medicine for the Practitioner. 1999 April; 63(4): 205-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10228747

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Keratosis pilaris/ulerythema ophryogenes and 18p deletion: is it possible that the LAMA1 gene is involved? Author(s): Zouboulis CC, Stratakis CA, Gollnick HP, Orfanos CE. Source: Journal of Medical Genetics. 2001 February; 38(2): 127-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11288714

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Keratosis punctata of the instep. Author(s): Kinsley-Scott TR, Young RJ 3rd, Meffert JJ. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 December; 72(6): 451-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700216

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Keratosis rubra pilaris responding to potassium titanyl phosphate laser. Author(s): Dawn G, Urcelay M, Patel M, Strong AM. Source: The British Journal of Dermatology. 2002 October; 147(4): 822-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12366447

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Lamin expression in normal human skin, actinic keratosis, squamous cell carcinoma and basal cell carcinoma. Author(s): Tilli CM, Ramaekers FC, Broers JL, Hutchison CJ, Neumann HA. Source: The British Journal of Dermatology. 2003 January; 148(1): 102-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534602

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LAV694, a new antiproliferative agent showing improved skin tolerability vs. clinical standards for the treatment of actinic keratosis. Author(s): Medina J, Picarles V, Greiner B, Elsaesser C, Kolopp M, Mahl A, Roman D, Vogel B, Nussbaumer P, Winiski A, Meingassner J, Fraissinette Ade B. Source: Biochemical Pharmacology. 2003 November 15; 66(10): 1885-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599546

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Lectin histochemistry in psoriasis, lichen planus and seborrheic keratosis. Author(s): Gao MY, Lin XR, Miao Q. Source: Chinese Medical Journal. 1992 December; 105(12): 1020-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1299550

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Lenticular acral keratosis in washerwomen. Author(s): Waxtein-Morgenstern L, Teixeira F, Cortes-Franco R, Vega-Memije ME, Ortiz-Plata A, Zamora-Hernandez C, Dominguez-Soto L. Source: International Journal of Dermatology. 1998 July; 37(7): 532-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9679695

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Keratosis

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Lesser metatarsal V-osteotomy for chronic intractable plantar keratosis. Retrospective analysis of 40 procedures. Author(s): Pontious J, Lane GD, Moritz JC, Martin W. Source: Journal of the American Podiatric Medical Association. 1998 July; 88(7): 323-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9680768

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Lessons on dermoscopy. Diagnosis: seborrheic keratosis. Author(s): Wang SQ, Katz B, Rabinovitz H, Kopf AW, Oliviero M. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 March; 26(3): 287-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10759811

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Lessons on dermoscopy: case #10. Diagnosis: the differential clinical diagnoses were dysplastic nevus, malignant melanoma, and lichen planus-like keratosis. Author(s): Wang SQ, Katz B, Rabinovitz H, Kopf AW, Oliviero M, Rao BK. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 November; 26(11): 1079-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096402

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Leukodermic macules in keratosis follicularis (Darier's disease). Author(s): Jacyk WK, Visser AJ. Source: International Journal of Dermatology. 1992 October; 31(10): 715-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1399201

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Leukonychia totalis associated with keratosis pilaris and hyperhidrosis. Author(s): Galadari I, Mohsen S. Source: International Journal of Dermatology. 1993 July; 32(7): 524-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8340192

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Levulan: the first approved topical photosensitizer for the treatment of actinic keratosis. Author(s): Jeffes EW. Source: The Journal of Dermatological Treatment. 2002; 13 Suppl 1: S19-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060513

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Lichen planoporitis: keratosis lichenoides chronica revisited. Author(s): Kossard S, Lee S. Source: Journal of Cutaneous Pathology. 1998 April; 25(4): 222-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9609142

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Lichen planus-like keratosis. A clinical and histological reexamination. Author(s): Prieto VG, Casal M, McNutt NS. Source: The American Journal of Surgical Pathology. 1993 March; 17(3): 259-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8434706

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Lichenoid keratosis: a clinicopathologic study of 17 patients. Author(s): Jang KA, Kim SH, Choi JH, Sung KJ, Moon KC, Koh JK. Source: Journal of the American Academy of Dermatology. 2000 September; 43(3): 511-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954665

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Linear melanonychia due to subungual keratosis of the nail bed: a report of two cases. Author(s): Baran R, Perrin C. Source: The British Journal of Dermatology. 1999 April; 140(4): 730-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233331

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Linkage analysis of keratosis follicularis spinulosa decalvans, and regional assignment to human chromosome Xp21.2-p22.2. Author(s): Oosterwijk JC, Nelen M, van Zandvoort PM, van Osch LD, Oranje AP, Wittebol-Post D, van Oost BA. Source: American Journal of Human Genetics. 1992 April; 50(4): 801-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1550124

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Lipid profile in actinic keratosis and basal cell carcinoma. Author(s): Vural P, Canbaz M, Sekcuki D, Murat A. Source: International Journal of Dermatology. 1999 June; 38(6): 439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10397583

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Localized keratosis follicularis associated with menotropin treatment and pregnancy. Author(s): Telang GH, Atillasoy E, Stierstorfer M. Source: Journal of the American Academy of Dermatology. 1994 February; 30(2 Pt 1): 271-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8288791

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Longitudinal erythronychia with distal subungual keratosis: onychopapilloma of the nail bed and Bowen's disease. Author(s): Baran R, Perrin C. Source: The British Journal of Dermatology. 2000 July; 143(1): 132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10886147

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Loss of heterozygosity in actinic keratosis, squamous cell carcinoma and sun-exposed normal-appearing skin in Japanese: difference between Japanese and Caucasians. Author(s): Kushida Y, Miki H, Ohmori M. Source: Cancer Letters. 1999 June 1; 140(1-2): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403556

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Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Author(s): Toomes C, James J, Wood AJ, Wu CL, McCormick D, Lench N, Hewitt C, Moynihan L, Roberts E, Woods CG, Markham A, Wong M, Widmer R, Ghaffar KA, Pemberton M, Hussein IR, Temtamy SA, Davies R, Read AP, Sloan P, Dixon MJ, Thakker NS. Source: Nature Genetics. 1999 December; 23(4): 421-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10581027

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Malignancy arising in seborrheic keratosis: a report of two cases. Author(s): Yap WM, Tan PH, Ong BH. Source: Ann Acad Med Singapore. 1997 March; 26(2): 235-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9208082

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Malignant fibrous histiocytoma in keratosis, ichthyosis, and deafness syndrome. Author(s): Carey AB, Burke WA, Park HM. Source: Journal of the American Academy of Dermatology. 1988 December; 19(6): 11246. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2849613

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Malignant melanoma appearing in a seborrhoeic keratosis. Author(s): Jones-Caballero M, Penas PF, Buezo GF, Fraga J, Aragues M. Source: The British Journal of Dermatology. 1995 December; 133(6): 1016-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8547029

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Malignant melanoma arising in a seborrheic keratosis. Author(s): Zabel RJ, Vinson RP, McCollough ML. Source: Journal of the American Academy of Dermatology. 2000 May; 42(5 Pt 1): 831-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10775864

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Malignant melanoma simulating a seborrheic keratosis: a case report. Author(s): Richert CA, Flynn KJ. Source: Dermatology Online Journal [electronic Resource]. 1997 March; 3(1): 5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9141366

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Malignant transformation of a clonal seborrhoeic keratosis. Author(s): Gallimore AP. Source: The British Journal of Dermatology. 1991 March; 124(3): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1826848

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Mast cells containing melanin granules in sublingual keratosis. Author(s): Tawfik AM, el-Labban NG, Barber P. Source: J Oral Pathol. 1987 March; 16(3): 108-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3114448

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Melanoma and seborrheic keratosis differentiation using texture features. Author(s): Deshabhoina SV, Umbaugh SE, Stoecker WV, Moss RH, Srinivasan SK. Source: Skin Res Technol. 2003 November; 9(4): 348-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641886

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Melanoma simulating seborrheic keratosis: a major dermoscopy pitfall. Author(s): Argenziano G, Rossiello L, Scalvenzi M, Staibano S, Ruocco E, Cicale L, Soyer HP. Source: Archives of Dermatology. 2003 March; 139(3): 389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622648

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Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis. Author(s): Dinehart SM, Nelson-Adesokan P, Cockerell C, Russell S, Brown R. Source: Cancer. 1997 March 1; 79(5): 920-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9041154

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Meyerson's phenomenon around a seborrhoeic keratosis. Author(s): Dawn G, Burden AD. Source: Clinical and Experimental Dermatology. 2002 January; 27(1): 73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952680

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Minimal incision approach to osteotomies of the lesser metatarsals. For treatment of intractable keratosis, metatarsalgia, and tailor's bunion. Author(s): White DL. Source: Clin Podiatr Med Surg. 1991 January; 8(1): 25-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2015532

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Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans: refinement of gene localization and evidence for genetic heterogeneity. Author(s): Oosterwijk JC, Richard G, van der Wielen MJ, van de Vosse E, Harth W, Sandkuijl LA, Bakker E, van Ommen GJ. Source: Human Genetics. 1997 October; 100(5-6): 520-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9341865

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Mosaic acral keratosis. Author(s): Jacyk K, Smith A. Source: Clinical and Experimental Dermatology. 1990 September; 15(5): 361-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2225540

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Multiple actinic keratosis and skin tumors secondary to hydroxyurea treatment. Author(s): Salmon-Ehr V, Grosieux C, Potron G, Kalis B. Source: Dermatology (Basel, Switzerland). 1998; 196(2): 274. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9568428

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Multiple fibroepithelial basal cell carcinoma of Pinkus associated with seborrheic keratosis in a nevoid distribution. Author(s): Rodriguez RA, Festa Neto C. Source: The Journal of Dermatology. 2000 May; 27(5): 341-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10875203

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Multiple small papular seborrheic keratosis. Author(s): Zhu WY. Source: Chinese Medical Journal. 1988 July; 101(7): 490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2976363

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Mutant p53 expression in solar keratosis: an immunohistochemical study. Author(s): Sim CS, Slater S, McKee PH. Source: Journal of Cutaneous Pathology. 1992 August; 19(4): 302-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1430469

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Mycosis fungoides masquerading as seborrhoeic keratosis. Author(s): Bazza MA, Ryatt KS, Dharmagunawardena PV. Source: The British Journal of Dermatology. 2002 December; 147(6): 1264-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452884

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Mycosis fungoides presenting as keratosis lichenoides chronica. Author(s): Bahadoran P, Wechsler J, Delfau-Larue MH, Gabison G, Revuz J, Bagot M. Source: The British Journal of Dermatology. 1998 June; 138(6): 1067-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9747377

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Nail changes in keratosis punctata. Author(s): Stone OJ, Mullins JF. Source: Archives of Dermatology. 1965 November; 92(5): 557-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5844399

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Natural history and management of keratosis, atypia, carcinoma-in situ, and microinvasive cancer of the larynx. Author(s): Gillis TM, Incze J, Strong MS, Vaughan CW, Simpson GT. Source: American Journal of Surgery. 1983 October; 146(4): 512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6625098

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Natural history of keratosis pilaris. Author(s): Poskitt L, Wilkinson JD. Source: The British Journal of Dermatology. 1994 June; 130(6): 711-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8011494

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Nevoid keratosis of the nipple. Author(s): Xifra M, Lagodin C, Wright D, Abbruzzese M, Woscoff A. Source: Journal of the American Academy of Dermatology. 1999 August; 41(2 Pt 2): 3256. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10426921

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New concepts on the origin of squamous cell carcinomas of the skin: solar (senile) keratosis with squamous cell carcinoma--a clinicopathologic and histochemical study. Author(s): Bendl BJ, Graham JH. Source: Proc Natl Cancer Conf. 1970; 6: 471-88. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5458117

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Nitric oxide and endothelin-1,2 in actinic keratosis and basal cell carcinoma: changes in nitric oxide/endothelin ratio. Author(s): Vural P, Erzengin D, Canbaz M, Selcuki D. Source: International Journal of Dermatology. 2001 November; 40(11): 704-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737437

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No evidence of human papillomavirus DNA in actinic keratosis. Author(s): Lu S, Syrjanen K, Havu VK, Syrjanen. Source: Archives of Dermatological Research. 1995; 287(7): 649-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8534128

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Nuclear bodies in keratosis arsenicalis. Author(s): Karasek J, Dubinin I. Source: Virchows Arch B Cell Pathol. 1969; 2(3): 171-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4978203

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Nuclear morphometry in solar keratosis. Author(s): Bozzo PD, Vaught LC, Alberts DS, Thompson D, Bartels PH. Source: Anal Quant Cytol Histol. 1998 February; 20(1): 21-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9513688

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Nucleolar organiser region (NOR) distribution as a diagnostic marker in oral keratosis, dysplasia and squamous cell carcinoma. Author(s): Warnakulasuriya KA, Johnson NW. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1993 February; 22(2): 77-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8445547

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Oblique metatarsal osteotomy for intractable plantar keratosis: 10-year follow-up. Author(s): Idusuyi OB, Kitaoka HB, Patzer GL. Source: Foot & Ankle International / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society. 1998 June; 19(6): 351-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9677076

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Occult basal cell carcinoma arising in seborrheic keratosis. Author(s): ENdoh K, Ohara M, Kosegawa G, Akasaka T. Source: The Journal of Dermatology. 1998 June; 25(6): 374-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9675344

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Ocular involvement in keratosis follicularis associated with retinitis pigmentosa. Clinicopathological case report. Author(s): Daicker B. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 1995; 209(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7715929

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Oil contact keratosis pilaris. Author(s): Georgouras K. Source: The Australasian Journal of Dermatology. 1985 December; 26(3): 108-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3835951

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On porokeratosis-Mibelli or keratosis excentrica. Author(s): Matsumoto SI. Source: G Ital Dermatol Minerva Dermatol. 1966 September-December; 107(5): 893-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6014676

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Opposing views of 2 academies about the nature of solar keratosis. Author(s): Ackerman AB. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 May; 71(5): 391-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12769406

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Oral and maxillofacial pathology case of the month. Snuff dippers keratosis or snuff pouch. Author(s): Wright JM. Source: Tex Dent J. 2003 December; 120(12): 1181, 1186-7. No Abstract Available. Erratum In: Tex Dent J. 2004 February; 121(2): 172. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14740396

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Oral minocycline improved keratosis follicularis squamosa (Dohi) and related disorder: bacterial factors are possibly involved in abberant keratinization. Author(s): Katayama I, Yokozeki H, Nishioka K. Source: The Journal of Dermatology. 1994 August; 21(8): 604-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7962961

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Oral treatment of keratosis follicularis with a new aromatic retinoid. Author(s): Orfanos CE, Kurka M, Strunk V. Source: Archives of Dermatology. 1978 August; 114(8): 1211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=677921

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Overexpression of p53 protein associated with proliferative activity and histological degree of malignancy in solar keratosis. Author(s): Shimizu T, Oga A, Murakami T, Muto M. Source: Dermatology (Basel, Switzerland). 1999; 199(2): 113-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10559575

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p16INK4a expression in actinic keratosis and Bowen's disease. Author(s): Salama ME, Mahmood MN, Qureshi HS, Ma C, Zarbo RJ, Ormsby AH. Source: The British Journal of Dermatology. 2003 November; 149(5): 1006-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632806

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Pagetoid variant of actinic keratosis with or without squamous cell carcinoma of sunexposed skin: a lesion simulating extramammary Paget's disease. Author(s): Mai KT, Alhalouly T, Landry D, Stinson WA, Perkins DG, Yazdi HM. Source: Histopathology. 2002 October; 41(4): 331-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383215

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Palmar plantar keratosis and unusual periodontal findings. Observations from a family of 4 members. Author(s): Fardal O, Drangsholt E, Olsen I. Source: Journal of Clinical Periodontology. 1998 February; 25(2): 181-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9495618

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Papular palmoplantar hyperkeratosis following chronic medical exposure to arsenic: human papillomavirus as a co-factor in the pathogenesis of arsenical keratosis? Author(s): Gerdsen R, Stockfleth E, Uerlich M, Fartasch M, Steen KH, Bieber T. Source: Acta Dermato-Venereologica. 2000 July-August; 80(4): 292-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11028865

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Pathologic quiz case: a 30-year-old man with a white plaque in the oral mucosa. Smokeless tobacco keratosis. Author(s): Sheth PD, Youngberg GA. Source: Archives of Pathology & Laboratory Medicine. 2004 January; 128(1): E17-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692835

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Pathology and pathobiology of the actinic (solar) keratosis. Author(s): Cockerell CJ. Source: The British Journal of Dermatology. 2003 November; 149 Suppl 66: 34-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616346

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Pemphigus foliaceus presenting as eruptive seborrheic keratosis and responding to oral gold treatment. Author(s): Bagheri MM, Alagheband M, Memar OM, Eiler DB. Source: J Drugs Dermatol. 2002 December; 1(3): 333-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851996

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Photodynamic therapy for actinic keratosis followed by 5-fluorouracil reaction. Author(s): Marcus L. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 October; 29(10): 1061-4; Discussion 1064-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974706

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Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. Author(s): Szeimies RM, Karrer S, Radakovic-Fijan S, Tanew A, Calzavara-Pinton PG, Zane C, Sidoroff A, Hempel M, Ulrich J, Proebstle T, Meffert H, Mulder M, Salomon D, Dittmar HC, Bauer JW, Kernland K, Braathen L. Source: Journal of the American Academy of Dermatology. 2002 August; 47(2): 258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140473

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Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. Author(s): Pariser DM, Lowe NJ, Stewart DM, Jarratt MT, Lucky AW, Pariser RJ, Yamauchi PS. Source: Journal of the American Academy of Dermatology. 2003 February; 48(2): 227-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12582393

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Photodynamic therapy with violet light and topical 6-aminolaevulinic acid in the treatment of actinic keratosis, Bowen's disease and basal cell carcinoma. Author(s): Dijkstra AT, Majoie IM, van Dongen JW, van Weelden H, van Vloten WA. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 November; 15(6): 550-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843215

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Pigmented and nested sebomatricoma or seborrheic keratosis with sebaceous differentiation? Author(s): Requena L, Kuztner H, Farina MC. Source: The American Journal of Dermatopathology. 1998 August; 20(4): 383-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9700378

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Pigmented squamous cell carcinoma of the cheek skin probably arising from solar keratosis. Author(s): Terada T, Yamagami J, Fugimoto A, Tanaka K, Sugiura M. Source: Pathology International. 2003 July; 53(7): 468-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828613

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Plasma antioxidant defense in actinic keratosis and basal cell carcinoma. Author(s): Vural P, Canbaz M, Selcuki D. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1999 September; 13(2): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10568487

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Prevalence of actinic keratosis in Japan. Author(s): Naruse K, Ueda M, Nagano T, Suzuki T, Harada S, Imaizumi K, Watanabe S, Ichihashi M. Source: Journal of Dermatological Science. 1997 September; 15(3): 183-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9302646

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Prevalence of melanoma clinically resembling seborrheic keratosis: analysis of 9204 cases. Author(s): Izikson L, Sober AJ, Mihm MC Jr, Zembowicz A. Source: Archives of Dermatology. 2002 December; 138(12): 1562-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472343

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Prevalence of solar damage and actinic keratosis in a Merseyside population. Author(s): Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Source: The British Journal of Dermatology. 2000 June; 142(6): 1154-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10848739

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Prevalence of solar damage and actinic keratosis in a Merseyside population. Author(s): Marks R. Source: The British Journal of Dermatology. 2001 February; 144(2): 437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11251601

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Progression of actinic keratosis to squamous cell carcinoma of the skin correlates with deletion of the 9p21 region encoding the p16(INK4a) tumor suppressor. Author(s): Mortier L, Marchetti P, Delaporte E, Martin de Lassalle E, Thomas P, Piette F, Formstecher P, Polakowska R, Danze PM. Source: Cancer Letters. 2002 February 25; 176(2): 205-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804749

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Proliferative actinic keratosis: three representative cases. Author(s): Goldberg LH, Chang JR, Baer SC, Schmidt JD. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 January; 26(1): 65-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10632689

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Quantitative assessment of Langerhans cells in actinic keratosis, Bowen's disease, keratoacanthoma, squamous cell carcinoma and basal cell carcinoma. Author(s): McArdle JP, Knight BA, Halliday GM, Muller HK, Rowden G. Source: Pathology. 1986 April; 18(2): 212-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3763243

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Radiation keratosis associated with exposure to a gold ring. Author(s): Helm KF, McAllister JM, Helm F. Source: Cutis; Cutaneous Medicine for the Practitioner. 1996 June; 57(6): 435-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8804849

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Radiation therapy for extensive actinic keratosis. Author(s): Barta U, Grafe T, Wollina U. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2000 July; 14(4): 293-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204519

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Radiation-induced squamous carcinoma arising within a seborrhoeic keratosis. Author(s): Suvarna SK, Bagary M, Glazer G. Source: The British Journal of Dermatology. 1993 April; 128(4): 443-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8494759

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Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis. Author(s): Jorizzo J, Stewart D, Bucko A, Davis SA, Espy P, Hino P, Rodriguez D, Savin R, Stough D, Furst K, Connolly M, Levy S. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 December; 70(6): 335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502122

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Rectal mucosa involvement in keratosis follicularis. Author(s): Klein A, Burns L, Leyden JJ. Source: Archives of Dermatology. 1974 April; 109(4): 560-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4819114

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Recurrent corneal ulcerations with perforation in keratosis follicularis (Darier-White disease). Author(s): Mielke J, Grub M, Besch D, Schlote T. Source: The British Journal of Ophthalmology. 2002 October; 86(10): 1192-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234910

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Refinement of the localisation of the X linked keratosis follicularis spinulosa decalvans (KFSD) gene in Xp22.13-p22.2. Author(s): Oosterwijk JC, van der Wielen MJ, van de Vosse E, Voorhoeve E, Bakker E. Source: Journal of Medical Genetics. 1995 September; 32(9): 736-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8544196

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Relationship of solar keratosis and history of skin cancer to objective measures of actinic skin damage. Author(s): Holman CD, Armstrong BK, Evans PR, Lumsden GJ, Dallimore KJ, Meehan CJ, Beagley J, Gibson IM. Source: The British Journal of Dermatology. 1984 February; 110(2): 129-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6696833

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Resident's page. Pathologic quiz. Case 1. Keratosis follicularis (Darier's disease). Author(s): Park YW, Harris AE. Source: Arch Otolaryngol. 1979 September; 105(9): 564-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=475656

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Role of endothelin-1 in hyperpigmentation in seborrhoeic keratosis. Author(s): Teraki E, Tajima S, Manaka I, Kawashima M, Miyagishi M, Imokawa G. Source: The British Journal of Dermatology. 1996 December; 135(6): 918-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8977712

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S100A protein expression in the distinction between lentigo maligna and pigmented actinic keratosis. Author(s): Ribe A, McNutt NS. Source: The American Journal of Dermatopathology. 2003 April; 25(2): 93-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12652189

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Sebaceous carcinoma arising on actinic keratosis. Author(s): Ansai S, Mihara I. Source: European Journal of Dermatology : Ejd. 2000 July-August; 10(5): 385-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10882948

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Seborrheic keratosis of conjunctiva simulating a malignant melanoma: an immunocytochemical study with impression cytology. Author(s): Tseng SH, Chen YT, Huang FC, Jin YT. Source: Ophthalmology. 1999 August; 106(8): 1516-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442897

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Seborrheic Keratosis-like lesions in patients with epidermodysplasia verruciformis. Author(s): Roncalli de Oliveira W, Neto CF, Rady PL, Tyring SK. Source: The Journal of Dermatology. 2003 January; 30(1): 48-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598709

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Selective inflammatory effect of systemic fluorouracil in actinic keratosis. Author(s): Nabai H, Mohindra R, Mehregan D. Source: Cutis; Cutaneous Medicine for the Practitioner. 1999 July; 64(1): 43-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10431671

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Solar keratosis is squamous cell carcinoma. Author(s): Ackerman AB. Source: Archives of Dermatology. 2003 September; 139(9): 1216-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12975172

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Squamous cell carcinoma arising within seborrheic keratosis. Author(s): Anderson PJ, Zuk JA, Rao GS, Berry RB. Source: Plastic and Reconstructive Surgery. 1998 August; 102(2): 453-5; Discussion 456-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9703085

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Successful treatment of multiple premalignant and malignant lesions in arsenical keratosis with a combination of acitretin and intralesional 5-fluorouracil. Author(s): Khandpur S, Sharma VK. Source: The Journal of Dermatology. 2003 October; 30(10): 730-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684956

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Summary of actinic keratosis studies with imiquimod 5% cream. Author(s): Tran H, Chen K, Shumack S. Source: The British Journal of Dermatology. 2003 November; 149 Suppl 66: 37-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616347

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Superficial spreading (and disappearing) seborrheic keratosis. Author(s): Winkelmann RK. Source: Cutis; Cutaneous Medicine for the Practitioner. 1999 April; 63(4): 235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10228754

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Suramin keratosis: a unique skin eruption in a patient receiving suramin for metastatic prostate cancer. Author(s): Kenner JR, Sperling LC, Waselenko J, Dawson N, Sau P, Moul JW. Source: The Journal of Urology. 1997 December; 158(6): 2245-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9366363

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The actinic (solar) keratosis: a 21st-century perspective. Author(s): Fu W, Cockerell CJ. Source: Archives of Dermatology. 2003 January; 139(1): 66-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533168

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The GSTM1 null genotype confers an increased risk for solar keratosis development in an Australian Caucasian population. Author(s): Carless MA, Lea RA, Curran JE, Appleyard B, Gaffney P, Green A, Griffiths LR. Source: The Journal of Investigative Dermatology. 2002 December; 119(6): 1373-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485442

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The nature of solar keratosis. Author(s): Silver SE. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 December; 72(6): 447; Author Reply 447, 450. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700215

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The nature of solar keratosis. Author(s): Powell ST. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 December; 72(6): 447; Author Reply 447, 450. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700214

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The nature of solar keratosis: a critical review in historical perspective. Author(s): Heaphy MR Jr, Ackerman AB. Source: Journal of the American Academy of Dermatology. 2000 July; 43(1 Pt 1): 138-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10863242

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The prevalence of seborrheic keratoses in people aged 15 to 30 years: is the term senile keratosis redundant? Author(s): Gill D, Dorevitch A, Marks R. Source: Archives of Dermatology. 2000 June; 136(6): 759-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10871940

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The use of topical fluorouracil to treat actinic keratosis. Author(s): Robins P, Gupta AK. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 August; 70(2 Suppl): 4-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12353679

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Topical treatment of actinic keratosis with fluorouracil: is irritation associated with efficacy? Author(s): Jorizzo J. Source: J Drugs Dermatol. 2004 January-February; 3(1): 21-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964743

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Treating keratosis pilaris. Author(s): Gerbig AW. Source: Journal of the American Academy of Dermatology. 2002 September; 47(3): 457. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196765

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Two brothers with keratosis follicularis spinulosa decalvans. Author(s): Alfadley A, Al Hawsawi K, Hainau B, Al Aboud K. Source: Journal of the American Academy of Dermatology. 2002 November; 47(5 Suppl): S275-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399750

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Ulerythema ophryogenes and keratosis pilaris in a child with monosomy 18p. Author(s): Zouboulis CC, Stratakis CA, Rinck G, Wegner RD, Gollnick H, Orfanos CE. Source: Pediatric Dermatology. 1994 June; 11(2): 172-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8041661

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Ulerythema ophryogenes and keratosis pilaris. Author(s): Patrizi A, Bianchi T, Orlandi C, Mazzanti L. Source: European Journal of Dermatology : Ejd. 2002 November-December; 12(6): 572. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503583

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Ultraviolet light downregulates CD95 ligand and TRAIL receptor expression facilitating actinic keratosis and squamous cell carcinoma formation. Author(s): Bachmann F, Buechner SA, Wernli M, Strebel S, Erb P. Source: The Journal of Investigative Dermatology. 2001 July; 117(1): 59-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442750

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Unilateral keratosis follicularis. Author(s): Moore JA, Schosser RH. Source: Cutis; Cutaneous Medicine for the Practitioner. 1985 May; 35(5): 459-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4006512

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Unilateral lesions in a patient with keratosis follicularis. Author(s): Erkek E, Atasoy P. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 September; 15(5): 491-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11763404

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Unilaterally generalized keratosis pilaris. Author(s): Ehsani A, Namazi MR, Barikbin B, Nazemi MJ. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 May; 17(3): 361-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702093

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Unilesional mycosis fungoides or lymphomatoid keratosis? Author(s): Kossard S. Source: Archives of Dermatology. 1997 October; 133(10): 1312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9382576

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Unprecedented giant seborrheic keratosis on the scalp. Author(s): Okazaki M, Ueda K. Source: Annals of Plastic Surgery. 1998 July; 41(1): 105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678483

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Update on actinic keratosis and Bowen's disease in clinical trial experience. Author(s): Salasche SJ. Source: The British Journal of Dermatology. 2003 November; 149 Suppl 66: 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616344

•

Utility of step sections: demonstration of additional pathological findings in biopsy samples initially diagnosed as actinic keratosis. Author(s): Carag HR, Prieto VG, Yballe LS, Shea CR. Source: Archives of Dermatology. 2000 April; 136(4): 471-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10768645

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Vascular variant of keratosis lichenoides chronica associated with hypothyroidism and response to tacalcitol and acitretin. Author(s): Nijsten T, Mentens G, Lambert J. Source: Acta Dermato-Venereologica. 2002; 82(2): 128-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12125942

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Violaceous papules in a linear and reticular pattern. Keratosis lichenoides chronica. Author(s): Amichai B, Grunwald MH, Halevy S. Source: Archives of Dermatology. 1995 May; 131(5): 609-10, 612-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7741551

•

Wax keratosis. Author(s): Black JI. Source: Eye Ear Nose Throat Mon. 1967 February; 46(2): 192-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6037440

Studies

•

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Zosteriform keratosis follicularis cleared with topically applied vitamin A acid. Author(s): Goette DK. Source: Archives of Dermatology. 1973 January; 107(1): 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4682533

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

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

7

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

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

A retrospective study of the effect of long-term topical application of retinaldehyde (0.05%) on the development of actinic keratosis. Author(s): Department of Dermatology, University Hospital, Geneva, Switzerland. [email protected] Source: Campanelli, A Naldi, L Dermatology. 2002; 205(2): 146-52 1018-8665

•

Actinic keratosis. Current treatment options. Author(s): Veteran Affairs Medical Center-Long Beach, Long Beach, California, USA. [email protected] Source: Jeffes, E W 3rd Tang, E H Am-J-Clin-Dermatol. 2000 May-June; 1(3): 167-79 11750561

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An ultrastructural study of the retention hyperkeratosis of experimentally induced comedones in rabbits: the effects of three comedolytics. Author(s): Department of Dermatology, Gyeongsang National University, Chinju, Korea. Source: Oh, C W Myung, K B J-Dermatol. 1996 March; 23(3): 169-80 0385-2407

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Anti-tumor effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in seborrheic keratosis. Author(s): Department of Dermatology, Yamaguchi University School of Medicine, Japan. Source: Asagami, C Muto, M Hirota, T Shimizu, T Hamamoto, Y J-Investig-DermatolSymp-Proc. 1996 April; 1(1): 94-6 1087-0024

•

Arsenic keratosis and pigmentation accompanied by multiple Bowen's disease and genitourinary cancer in a psoriasis patient. Author(s): Department of Dermatology, Seoul National University College of Medicine, Korea. Source: Park, J Y Rim, J H Choe, Y B Youn, J I J-Dermatol. 2002 July; 29(7): 446-51 03852407

•

Bilateral nipple hyperkeratosis treated successfully with topical isotretinoin. Author(s): Department of Dermatology, Faculty of Medicine, Gazi University, Ankara, Turkey. Source: Toros, P Onder, M Gurer, M A Australas-J-Dermatol. 1999 November; 40(4): 2202 0004-8380

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Etretinate treatment in disseminated porokeratosis. Source: Danno, K Yamamoto, M Yokoo, T Ohta, M Ohno, S J-Dermatol. 1988 October; 15(5): 440-4 0385-2407

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Hyperkeratosis of the nipple: report of two cases. Author(s): Department of Dermatology, Akdeniz University Medical Faculty, Antalya, Turkey. Source: Alpsoy, E Yilmaz, E Aykol, A J-Dermatol. 1997 January; 24(1): 43-5 0385-2407

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Keratosis lichenoides chronica. Author(s): Scripps Research Institute, La Jolla, California 92037, USA. [email protected] Source: KonstantiNovember, K N Sondergaard, J Izuno, G Obreshkova, E J-Am-AcadDermatol. 1998 February; 38(2 Pt 2): 306-9 0190-9622

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Lichenoid keratosis: a clinicopathologic study of 17 patients. Author(s): Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. Source: Jang, K A Kim, S H Choi, J H Sung, K J Moon, K C Koh, J K J-Am-AcadDermatol. 2000 September; 43(3): 511-6 0190-9622

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Nevoid hyperkeratosis of the areola with histopathological features mimicking mycosis fungoides. Author(s): Department of Dermatology, Clinica Universitaria Puerta de Hierro, Madrid, Spain. [email protected] Source: Roustan, Gaston Yus, Evanisto S Simon, Angel Eur-J-Dermatol. 2002 JanFebruary; 12(1): 79-81 1167-1122

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Plasma antioxidant defense in actinic keratosis and basal cell carcinoma. Author(s): Department of Biochemistry and Clinical Biochemistry, Istanbul Medical Faculty, Turkey. Source: Vural, P Canbaz, M Selcuki, D J-Eur-Acad-Dermatol-Venereol. 1999 September; 13(2): 96-101 0926-9959

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Postsurgical dyskeratosis treated with topical and parenteral administration of vitamin A. Author(s): I Cattedra di Oftalmologia, Universita degli Studi di Napoli Federico II, Italia. Source: Del Prete, A Ferrante, M Troisi, S Mele, V Reccia, R Sebastiani, A Ophthalmologica. 1997; 211(2): 101-3 0030-3755

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Selective loss of chondroitin 6-sulphate from basement membrane during progression from actinic keratosis to squamous cell carcinoma. Author(s): Department of Dermatology, Niigata University School of Medicine, Japan. Source: Kazama, T Fujiwara, K Ito, M Arch-Dermatol-Res. 1994; 286(2): 130-2 0340-3696

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Sepsis as an unusual event in dyskeratosis follicularis. Author(s): Department of Dermatovenerology, Zagreb University Hospital Center, Salata 4, 10000 Zagreb, Croatia. [email protected] Source: Milavec Puretic, V Lipozencic, J Sustic, N Pecina Slaus, N Croat-Med-J. 2001 February; 42(1): 64-6 0353-9504

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Treatment of arsenical keratosis and Bowen's disease with acitretin. Author(s): Department of Dermatology, Akdeniz University School of Medicine, Antalya, Turkey. [email protected] Source: Yerebakan, Ozlem Ermis, Oya Yilmaz, Ertan Basaran, Erdal Int-J-Dermatol. 2002 February; 41(2): 84-7 0011-9059

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Vascular variant of keratosis lichenoides chronica associated with hypothyroidism and response to tacalcitol and acitretin. Author(s): Department of Dermatology, University Hospital Antwerp, Belgium. Source: Nijsten, T Mentens, G Lambert, J Acta-Derm-Venereol. 2002; 82(2): 128-30 00015555

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Zinc responsive alopecia and hyperkeratosis in Angora goats. Author(s): Department of Agriculture, Albany, Western Australia. Source: Reuter, R Bowden, M Besier, B Masters, H Aust-Vet-J. 1987 November; 64(11): 351-2 0005-0423

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

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

•

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

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

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

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

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

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

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

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

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

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

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

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

•

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

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

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

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

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The following is a specific Web list relating to keratosis; 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: •

Minerals Retinol Source: Integrative Medicine Communications; www.drkoop.com Vitamin A (Retinol) Source: Integrative Medicine Communications; www.drkoop.com

•

Food and Diet Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com

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

A pilot study of the diagnosis and treatment of impaired skin integrity: dry skin in older persons. Author(s): Hardy MA. Source: Nursing Diagnosis : Nd : the Official Journal of the North American Nursing Diagnosis Association. 1990 April-June; 1(2): 57-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2357430

•

A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Author(s): Darlington S, Williams G, Neale R, Frost C, Green A. Source: Archives of Dermatology. 2003 April; 139(4): 451-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707092

•

Abnormal essential fatty acid metabolism in Darier's disease. Author(s): Oxholm A, Oxholm P, da Cunha Bang F, Horrobin DF.

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Source: Archives of Dermatology. 1990 October; 126(10): 1308-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1977367 •

Acquired digital fibrokeratoma. Author(s): LoBuono P, Jothikumar T, Kornblee L. Source: Cutis; Cutaneous Medicine for the Practitioner. 1979 July; 24(1): 50-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=477378

•

Acquired linear naevus showing histological features of keratosis follicularis. Author(s): Leeming JA. Source: The British Journal of Dermatology. 1969 February; 81(2): 128-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5767067

•

Acute graft-versus-host disease resulting from normal donor blood transfusions. Author(s): Burns LJ, Westberg MW, Burns CP, Klassen LW, Goeken NE, Ray TL, Macfarlane DE. Source: Acta Haematologica. 1984; 71(4): 270-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6426240

•

Allergy and skin diseases in musicians. Author(s): Lombardi C, Bottello M, Caruso A, Gargioni S, Passalacqua G. Source: Allerg Immunol (Paris). 2003 February; 35(2): 52-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12674039

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Arsenic and Ayurveda. Author(s): Treleaven J, Meller S, Farmer P, Birchall D, Goldman J, Piller G. Source: Leukemia & Lymphoma. 1993 July; 10(4-5): 343-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7693104

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Arsenic keratosis and pigmentation accompanied by multiple Bowen's disease and genitourinary cancer in a psoriasis patient. Author(s): Park JY, Rim JH, Choe YB, Youn JI. Source: The Journal of Dermatology. 2002 July; 29(7): 446-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184646

•

Arsenic toxicity from homeopathic treatment. Author(s): Chakraborti D, Mukherjee SC, Saha KC, Chowdhury UK, Rahman MM, Sengupta MK. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(7): 963-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705842

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•

Atypical lichen planus induced by native medicine. Author(s): Soyinka F. Source: The British Journal of Dermatology. 1973 April; 88(4): 341-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4712216

•

Betel-nut-associated cancer: report of case. Author(s): Fendell LD, Smith JR. Source: J Oral Surg. 1970 June; 28(6): 455-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5266466

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Case report: multiagent chemotherapy of Hodgkin's disease associated with red cell aplasia, acquired ichthyosis and anhidrosis. Author(s): Homeida M, Mukhtar ED, Daneshmend T, Omer A. Source: East Afr Med J. 1987 May; 64(5): 339-41. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3125033

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Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary. Author(s): Rahman MM, Chowdhury UK, Mukherjee SC, Mondal BK, Paul K, Lodh D, Biswas BK, Chanda CR, Basu GK, Saha KC, Roy S, Das R, Palit SK, Quamruzzaman Q, Chakraborti D. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(7): 683-700. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11778666

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Chronic arsenic toxicity: clinical features, epidemiology, and treatment: experience in West Bengal. Author(s): Guha Mazumder DN. Source: Journal of Environmental Science and Health. Part A, Toxic/Hazardous Substances & Environmental Engineering. 2003 January; 38(1): 141-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635824

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Citrus pulp for cattle. Author(s): Arthington JD, Kunkle WE, Martin AM. Source: Vet Clin North Am Food Anim Pract. 2002 July; 18(2): 317-26, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235663

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Clearance of ichthyosis linearis circumflexa with balneophototherapy. Author(s): Gambichler T, Senger E, Altmeyer P, Hoffmann K. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2000 September; 14(5): 397-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11305383

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Common ear diseases: recognition and management. Author(s): Keim RJ. Source: Postgraduate Medicine. 1977 May; 61(5): 72-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=857250

•

Effect of keratolytic drugs on oral hyperkeratosis in Syrian hamsters. Author(s): Capodanno JA, Hayward JR. Source: Journal of Dental Research. 1966 May-June; 45(3): 951-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5222500

•

Keratosis circumscripta. A distinct dermatological entity or a variant of psoriasis? Author(s): Soyinka F, Laja AO. Source: Dermatologica. 1978; 156(6): 341-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=658574

•

Keratosis lichenoides chronica in childhood. Author(s): Redondo P, Solano T. Source: Clinical and Experimental Dermatology. 2002 June; 27(4): 283-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139671

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Papular palmoplantar hyperkeratosis following chronic medical exposure to arsenic: human papillomavirus as a co-factor in the pathogenesis of arsenical keratosis? Author(s): Gerdsen R, Stockfleth E, Uerlich M, Fartasch M, Steen KH, Bieber T. Source: Acta Dermato-Venereologica. 2000 July-August; 80(4): 292-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11028865

•

Rapid development of disseminated superficial porokeratosis after transplant induction therapy. Author(s): Fields LL, White CR Jr, Maziarz RT. Source: Bone Marrow Transplantation.

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/

•


•

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

•

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

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

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

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•

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

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

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

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

•

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

•

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

•

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

The following is a specific Web list relating to keratosis; 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 Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum 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. CLINICAL TRIALS AND KERATOSIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning keratosis.

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

Celecoxib in Preventing Skin Cancer in Patients With Actinic Keratoses Condition(s): actinic keratosis Study Status: This study is currently recruiting patients. Sponsor(s): UAB Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of celecoxib may be an effective way to prevent actinic keratoses. PURPOSE: Randomizedphase II/III trial to determine the effectiveness of celecoxib in preventing skin cancer in patients who have actinic keratoses. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027976

•

Eflornithine With or Without Triamcinolone in Preventing Nonmelanoma Skin Cancer in Patients With Actinic Keratosis Condition(s): actinic keratosis; squamous cell carcinoma of the skin; prevention of skin cancer; basal cell carcinoma of the skin Study Status: This study is no longer recruiting patients.

8

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): National Cancer Institute (NCI); Arizona Cancer Center Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Eflornithine with or without triamcinolone may be effective in preventing nonmelanoma skin cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of eflornithine with or without triamcinolone in preventing nonmelanoma skin cancer in patients who have actinic keratosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021294 •

Green Tea Extract in Treating Patients With Actinic Keratosis Condition(s): actinic keratosis; squamous cell carcinoma of the skin; prevention of skin cancer; basal cell carcinoma of the skin Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Chao Family Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Green tea extract contains ingredients that may inhibit the growth of actinic keratosis. PURPOSE: Randomized phase II trial to determine the effectiveness of green tea extract in treating patients who have actinic keratosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005097

•

National Registry for Ichthyosis and Related Disorders Condition(s): Hyperkeratosis, Epidermolytic; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Ichthyosis, Lamellar; Ichthyosis, X-Linked Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The ichthyoses are a family of genetic skin diseases characterized by dry, thickened, scaling skin. Dermatologists estimate that there are at least twenty varieties of ichthyosis, with a wide range of severity and associated symptoms. This registry is designed to identify people in the United States with the ichthyoses and other related disorders and to collect information about their skin ailment and how it has affected them. The database is available for review by approved research applicants. The registry is confidential and provides researchers a way to share information about studies and trials with potential participants while maintaining participants' privacy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074685

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•

Photodynamic Therapy in Treating Patients With Skin Cancer Condition(s): basal cell carcinoma of the skin; squamous cell carcinoma of the skin; actinic keratosis Study Status: This study is suspended. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Photodynamic therapy uses light and drugs that make cancer cells more sensitive to light to kill tumor cells. Photodynamic therapy using aminolevulinic acid may be effective in treating patients with skin cancer. PURPOSE: Randomized phase II trial to study the effectiveness of photodynamic therapy that includes aminolevulinic acid in treating patients with skin cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002975

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Study of Scaling Disorders and Other Inherited Skin Diseases Condition(s): Genetic Skin Disease; Keratosis Follicularis; Lamellar Ichthyosis Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The purpose of this study is to identify the genes responsible for certain scaling disorders and other inherited skin diseases and to learn about the medical problems they cause. In some cases, these may include problems affecting organs other than the skin, such as the eyes, teeth and bones. Patients with inherited skin disorders, including Darier's disease (keratosis follicularis), lamellar ichthyosis, epidermolysis bullosa, cystic acne, and others, and their relatives may be eligible for this study. Patients will have a medical history, physical examination with particular emphasis on the skin, and routine blood tests. Additional procedures for patients and unaffected relatives may include: 1. Blood sample collection 2. Dental exam with X-ray of the jaw 3. Eye examination 4. X-rays of the skull, ribs, chest, hands, feet, spine, arms, or legs 5. Bone density scan 6. Photographs of the skin 7. Skin biopsies (removal of a small tissue sample under local anesthetic) 8. Buccal sample (gentle brushing inside the cheek to collect a cell sample) for gene studies Patients who request the results of their gene testing will be provided this information. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001292

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The Evaluation of Oral Acitretin in the Treatment of Psoriasis, Cutaneous Disorders of Keratinization, Multiple Basal Cell Carcinomas and Other Retinoid Responsive Diseases Condition(s): Basal Cell Carcinoma; Keratosis Palmaris et Plantaris; Psoriasis Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI)

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Purpose - Excerpt: This is a continuing study which evaluates the long-term safety and efficacy of oral acitretin in an open manner in the treatment of psoriasis, cutaneous disorders of keratinization, multiple basal cell carcinomas and other retinoid responsive diseases. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005660

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 5. PATENTS ON KERATOSIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “keratosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on keratosis, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Keratosis By performing a patent search focusing on keratosis, 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

9Adapted

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

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on keratosis: •

Compositions and methods of treatment using peat derivatives Inventor(s): Harnisch; James P. (Mercer Island, WA), Hart; Ralph M. (Lake Forest Park, WA), Jones; Herman L. (Wenatchee, WA), Jones; Veronica Lee Egelkrout (Wenatchee, WA), Kenny; Margaret A. (Edmonds, WA), Loev; Bernard (Medford, NJ), Malik; Sohail (Redmond, WA) Assignee(s): C-p Technology Limited Partnership (mill Creek, Wa) Patent Number: 6,267,962 Date filed: June 30, 1997 Abstract: Novel compositions containing at least one biologically active component derived from peat or similar composition, methods for their preparation and therapeutic uses for a variety of diseases, injuries, and conditions, including wound healing, pain, itch, inflammation, abnormal cell proliferation, or infections caused by fungal, bacterial, rickettsial or viral agents, psoriasis, allergic and other dermatitis, pruritis, eczema, actinic keratosis and similar conditions. In addition, the compositions can be used as diuretics, antiarrhythmics, and cardiac-stimulating agents, as well as for the treatment of mammalian diseases and disorders, including multiple drug resistance, cancers, asthma, rheumatoid arthritis, pain, wound healing, fungal disorders, and other inflammatory disorders. The compositions are derivable from peat or peat-related substances and may alternatively be synthetically produced. Excerpt(s): This invention relates to novel compositions, methods of isolation and synthesis, and pharmaceutical uses of materials derived from peat. These compositions may be used for the treatment of wounds and for diseases and disorders such as pruritis, psoriasis, allergic and other dermatitis, eczema, and actinic keratosis. The compositions may be suitable for accelerating wound healing; relieving pain, itch or inflammation; reducing abnormal proliferative cell growth, particularly keratinocytes, of the skin and for hyperplastic and neoplastic conditions of other epithelial systems in the human body; and providing antifungal, antiviral, or antibacterial activity. In addition, the composition can be used as a diuretic, antiarrhythmic, and cardiac-stimulating agent. It may also be used as a therapeutic agent in the treatment of multiple drug resistance, malignancies, asthma, rheumatoid arthritis, fungal infections, and inflammatory disorders. Normal skin epidermis is a complex epithelial tissue containing keratinocytes that are proliferating, differentiating, and desquamating. Many common diseases of the skin epidermis, such as psoriasis, squamous cell carcinoma, keratoacanthoma, actinic keratosis, and warts, are characterized by localized abnormal proliferation and growth that is localized. For example, in psoriasis, which is characterized by scaly, red, elevated plaques on the skin, the keratinocytes are known to proliferate much more rapidly than normal. Eczema is a superficial inflammatory process involving primarily the epidermis, marked early by redness, itching, minute papules and vesicles, weeping, oozing, and crusting, and later by scaling, lichenification, and often pigmentation. Clinical use of available treatments for diseases involving epidermal conditions is often limited by toxicity, either systemic or local. For example, methotrexate, although generally effective for treating epidermal conditions when administered orally, is rarely administered orally for fear of hepatic or bone marrow toxicity. Topical application of methotrexate has minimal or no therapeutic effect. Similarly, although topical application of 5-fluorouracil may be an effective treatment

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for psoriasis, it is generally considered to be unacceptably irritating. Steroid therapy, though effective, is associated with adverse side effects that are potentially so numerous or serious that prolonged use is discouraged. Photochemotherapy with psoralens and ultraviolet light, or PUVA (psoralens and UV treatment), is generally effective for treatment of epidermal conditions, but it is inconvenient to administer and causes side effects and may even cause photomutagenic and photocarcinogenic reactions. Web site: http://www.delphion.com/details?pn=US06267962__ •

Cosmetic/dermatological w/o emulsions highly concentrated in hydroxy acids Inventor(s): Allec; Josiane (Antibes, FR), Ferrandis; Agnes (Mougins, FR), Preuilh; Isabelle (Antibes, FR), Willcox; Nathalie (Le Rouret, FR) Assignee(s): Centre International DE Recherches Dermatologiques Galderma (valbonne, Fr) Patent Number: 5,863,544 Date filed: December 14, 1995 Abstract: Topically applicable cosmetic/dermatological compositions well suited for the therapeutic treatment or care of human skin, nails, hair and/or of the scalp, in particular for treating and/or preventing xerosis, ichthyosis, actinic keratosis and/or photoinduced cutaneous aging, comprise a water-in-oil emulsion containing (a) at least 10% by weight of at least one hydroxy acid, (b) an effective emulsifying amount of at least one polyoxyalkylenated silicone, and (c) an effective coemulsifying amount of at least one polyol alkyl ester, polyol alkyl ether or oxyalkylenated alkyl ether, with the proviso that the subject compositions are devoid of any C.sub.1 -C.sub.4 alkanol. Excerpt(s): The present invention relates to novel cosmetic/dermatological compositions for topical application, comprising water-in-oil emulsions containing a high content of hydroxy acids, for therapeutic treatment or care of the skin, nails or hair and/or of the scalp, and to the use of same, in particular for treating and/or preventing xerosis, ichthyosis, actinic keratosis and/or photoinduced cutaneous aging. It is known to this art to employ hydroxy acids for preventing or reducing the dermatological signs of aging of the skin and/or of hair, which are due to factors that are intrinsic to aging or else to external factors, such as, especially, UV irradiation, air pollution, wind, cold, heat and cigarette smoke. These are also known active agents for treating dermatological afflictions related to a disorder of the keratinization of the skin, nails and/or hair, such as especially acne, xerosis, ichthyosis and actinic keratosis. However, these hydroxy acids are difficult to formulate as an emulsion in cream or milk form. Indeed, when they are incorporated in a concentrated amount, the hydroxy acids render the formulation unstable and therefore difficult to commercially exploit. Web site: http://www.delphion.com/details?pn=US05863544__

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Hyaluronic acid and its salt for treating skin diseases Inventor(s): Ikeya; Hitoshi (Machida, JP), Kitagawa; Hironoshin (Machida, JP) Assignee(s): Denki Kagaku Kogyo Kabushiki Kaisha (tokyo, Jp) Patent Number: 5,728,391 Date filed: December 5, 1995

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Abstract: An agent for treating a skin disease selected from the group consisting of a contact dermatitis treating agent, a xerosis senilis treating agent, an asteatosis treating agent, a housewives eczema treating agent, a keratosis treating agent, an eczema chronicum treating agent, a miliaria treating agent and a diaper rash treating agent, which contains hyaluronic acid and/or its salt having an average molecular weight of from 800,000 to 4,000,000, as an active ingredient. Excerpt(s): The present invention relates to agents for treating skin diseases. More particularly, it relates to agents for treating skin diseases, which contain hyaluronic acid and/or its salt (hereinafter generally referred to as the hyaluronic acid) as an active ingredient and which have excellent moisturizing effects, skin-forming effects, antiinflammatory effects, dry skin treating effects and irritation-relief effects. Heretofore, for the treatment of skin diseases such as xerosis senilis and miliaria, an adrenocortical steroid agent, an urea ointment, a heparinoid from animal organs, or a vaselin-base ointment such as an azulene ointment, has been used. The adrenocortical steroid agent has strong pharmaceutical effects, but is likely to bring about various side effects. The urea ointment is excellent in the moisturizing effects, but sometimes brings about side effects such as irritation or smarting. The heparinoid from animal organs sometimes brings about a contact dermatitis as a side effect. Therefore, theses agents have had problems from the viewpoint of safety. On the other hand, the vaselin-base ointment such as an azulene ointment presents an unpleasant feeling such as a sticky feeling, upon application, and at the same time, a foreign matter such as dust is likely to deposit thereon. Thus, such an ointment has had a problem with respect to the feeling upon application. From these viewpoints, there has been no treating agent for skin diseases, which is capable of presenting fully satisfactory curing effects against the abovementioned diseases. Web site: http://www.delphion.com/details?pn=US05728391__ •

Lipids from omentum and methods for cosmetic use Inventor(s): Catsimpoolas; Nicholas (Newton Centre, MA), Griffith; Ann L. (Newton Centre, MA), Kamarei; Ahmad R. (Arlington, MA), Sinn; Robert S. (New York, NY) Assignee(s): Angio-medical Corporation (avenue of the Americas, Ny) Patent Number: 4,879,114 Date filed: December 20, 1985 Abstract: 36 Lipid extracts and lipid fractions from mammalian omenta containing mostly lipids are used cosmetically for skin conditions, skin care and cosmetic products which products have skin softening applications without skin irritation, greasiness or mutagenic effect. These materials with and without ganglioside are used for skin conditions such as keratosis, white spots and the like. Excerpt(s): This application concerns cosmetic use of isolated and purified lipids from mammalian omenta. This invention relates to cosmetic applications as in creams and lotions for skin care. The patent literature shows various cosmetic claims containing various waxes, oils, alcohols and fats. Some of these compositions are used as cosmetic bases see U.S. Pat. No. 2,532,206 issued Nov. 28, 1950 to Taub et al. U.S. Pat. No. 2,988,484 issued to Barsky et al. June 13, 1961 and U.S. Pat. No. 3,826,845 issued July 30, 1974 to Tsunesuke Suyama et al., U.S. Pat. No. 3,846,556 issued Nov. 5, 1974 to Handjani nee Vila et al. and U.S. Pat. No. 4,401,664 issued Aug. 30, 1983 to Ingeborg Scheuffgen. Many of these cosmetics are used to increase elasticity and tightening of the skin and

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often may have herbal or other plant extracts included. We note U.S. Pat. No. 4,382,961 issued May 10, 1983 to Nedeczky nee Gardy et al. using sunflower extract. Web site: http://www.delphion.com/details?pn=US04879114__ •

Method and composition for the treatment of seborrheic keratosis Inventor(s): Tenta; Louis T. (6007 N. Sheridan Rd., Chicago, IL 60660) Assignee(s): None Reported Patent Number: 4,112,121 Date filed: August 3, 1977 Abstract: Method and composition for the chemexfoliation (chemical exfoliation) of seborrheic keratosis and related conditions, the composition consisting essentially of an alkali metal or ammonium phenate, a monohydric alcohol, a polyhydric alcohol humectant and a gelling agent. Excerpt(s): This invention is in the field of topical compositions for the treatment of seborrheic keratosis and includes an alkali metal or ammonium phenate, a monohydric alcohol solvent, a polyhydric alcohol humectant which absorbs moisture from the air to initiate the exfoliation reaction, and a gelling agent which improves the adherence of the composition to the skin. In U.S. Pat. No. 3,821,370, I described a topical composition for use in the treatment of various skin conditions, including seborrheic keratosis. This patent disclosed a composition containing from 20 to 60 parts of an inhibited phenol calculated as potassium phenolate, 1 part of a salicylate calculated as sodium salicylate, 5 parts of resorcinol, and 4 parts of a zinc compound calculated as zinc sulfate. In a later filed application, now U.S. Pat. No. 3,949,072, I described a composition containing an inhibited phenol, a salicylate, a zinc compound and resorcinol, all dissolved in a nonaqueous solvent which included a hydrophilic non-toxic lower aliphatic alcohol. The advantage of the composition described in this later patent was the use of significantly lower amounts of the phenolate than in the previous patent. Web site: http://www.delphion.com/details?pn=US04112121__

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Method for the treatment of hyperproliferative epithelial skin diseases by topical application of hydroxylated aromatic protein cross-linking compounds Inventor(s): Burke, Jr.; Terrence R. (Bethesda, MD), Stanwell; Caroline (Bethesda, MD), Yuspa; Stuart H. (Bethesda, MD) Assignee(s): The United States of America AS Represented by the Department of Health (washington, Dc) Patent Number: 5,610,185 Date filed: February 17, 1995 Abstract: The present invention relates to a method of treating hyperproliferative epithelial lesions by topical administration. The method prevents growth and actively cross-links these aberrant cells, thereby killing the cells. The present invention is useful in control and prevention of hyperproliferative epithelial disorders, such as HPVinfected cell lesions, actinic keratosis, melanomas, and malignant and pre-malignant carcinomas.

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Excerpt(s): The present invention relates to a novel method of treating hyperproliferative epithelial diseases. In particular, a specific class of compounds is used in the topical treatment of skin lesions. These compounds are in general, hydroxylated aromatic protein crosslinking agents and are useful for a wide range of skin diseases. Non-neoplastic and neoplastic hyperproliferative skin disorders are prevalent and present an everincreasing burden to health care providers. Increased exposure of skin to UV light in recent years has contributed to the marked increased incidence of premalignant lesions such as actinic keratoses. Superficial squamous and basal cell carcinoma levels now exceed 700,000 cases per year in the US (American Cancer Society, 1994). Similarly warts (plantar and genital) and other localized hyperproliferative conditions of the skin are extremely prevalent. At the present time, there are insufficient effective treatment options available to the clinician. Treatment modalities for these conditions include surgical resection or freezing the tissue to destroy rogue cells. These methods are not always the treatment of choice as they are non-selective and, hence, hyperproliferative cells can remain to cause recurrence or normal tissue can be damaged with the development of scar tissue. These techniques are often painful and therefore unacceptable to patients. Exfoliative acidic compounds such as salicylates are used topically to desquamate hyperproliferative skin lesions and kill cells directly, particularly in the treatment of plantar warts. However this treatment is not selective for hyperproliferative cells and is not always curative. The topical application of cytotoxic agents such as bleomycin and 5-fluorouracil (5FU) is used for the treatment of premalignant and malignant lesions and podophyllotoxin for genital warts. There is some concern about the toxicity of these agents, which work by direct cytotoxicity, interfering with DNA synthesis of proliferating cells by a variety of mechanisms. These agents have to be applied extremely carefully to avoid contact with normal skin since normal skin can be irreparably damaged, and systemic absorption of these compounds may also provide a significant risk to the patient. Retinoids, which are vitamin A derivatives, are a recent introduction for the treatment of neoplastic skin lesions. Unfortunately, these compounds are suppressive rather than curative and withdrawal of the drug leads to recurrence. Web site: http://www.delphion.com/details?pn=US05610185__ •

Method for treating actinic keratosis with cytotoxic agents Inventor(s): Pearlman; Dale L. (21063 Christensen Dr., Cupertino, CA 95014) Assignee(s): None Reported Patent Number: 4,820,711 Date filed: May 15, 1987 Abstract: A method for treating actinic keratosis comprising applying an effective amount of a cytotoxic drug dispersed in a pharmaceutically acceptable vehicle containing a penetrating solvent for the drug, the drug being applied to the skin area having the actinic keratosis growth without occlusion in pulses at an interval of once every from 3 to 30 days and preferably at an interval of from 4 to 14 days. Optimally, the penetrating solvent is free from toxic effects, such as AZONE or similar substituted azacycloalkyl-2-ones, tertiary amine oxides, and the like. Excerpt(s): This invention relates to the therapeutic treatment of skin disorders such as actinic keratoses. In particular, this invention relates to an effective regimen for successfully treating actinic keratoses with a cytotoxic agent such as fluorouracil (5fluorouracil or 5--FU) in a penetrating solvent. Actinic keratosis is a horny growth, such

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as a wart or callosity on the skin, generally sharply outlined, red or skin-colored, flat or elevated, verrucous or keratotic growth, which may develop into a cutaneous horn, or may give rise to squamous cell carcinoma. It usually affects the middle-aged or elderly, especially those of fair complexion and is caused by excessive exposure to the sun. Traditional treatments of actinic keratosis have included daily or more frequent application of cytotoxic agents such as fluorouracil with or without an occlusive dressing, dissolved or suspended in an ointment, lotion, or glycol solvent applied to the affected area. Penetrating solvents have been investigated for enhancing percutaneous absorption of fluorouracil in an effort to more successfully treat more resistive conditions. Web site: http://www.delphion.com/details?pn=US04820711__ •

Method for treating epithelial precancerous lesions with topical inidazoles Inventor(s): Brugnara; Carlo (Newton Highlands, MA), Halperin; Jose (Brookline, MA), Haynes; Harley (Bedford, MA) Assignee(s): President & Fellows of Harvard College (cambridge, Ma) Patent Number: 5,556,871 Date filed: April 24, 1995 Abstract: A method of treating epithelial precancerous lesions is provided. The method involves the administration of certain imidazoles to an epithelial precancerous lesion. The preferred imidazoles are clotrimazole, miconazole, econazole and ketoconazole. The method of the invention is especially useful in treating actinic keratosis. Excerpt(s): Precancerous skin lesions of keratinocytes are those areas of skin in which tissue shows the tendency to develop into cancer, although the tissue in its present state is not a cancer. Epithelial precancerous lesions include actinic keratosis (also called solar keratosis or senile keratosis), hypertrophic actinic keratosis, Bowenoid actinic keratosis, arsenical keratosis, hydrocarbon keratosis, thermal keratosis, radiation keratosis, chronic scar keratosis, viral keratosis, Bowen's disease, erythroplaquia of queyrat, oral erythroplaquia, leukoplakia, and intraepidermal epithelialoma. Actinic keratosis is the most common epithelial precancerous lesion among fair skinned individuals. It is usually present as lesions on the skin which may or may not be visually detectable. The size and shape of the lesions varies. It is a photosensitive disorder and may be aggravated by exposure to sunlight. If left untreated, the lesions may proceed to form atypical squamous cells, one example of which is Bowenold actinic keratosis. Bowenoid actinic keratosis is another form of an epithelial precancerous lesion. In some cases, the lesions may develop into an invasive form of squamous cell carcinoma and may pose a significant threat of metastasis. Actinic keratosis is characterized by an inflammatory infiltration of lymphocytes, histocytes and a variable number of plasma cells. It further is characterized by proliferation of keratinocytes. There also is evidence that actinic keratosis has mutations of the P53 and H-RAS oncogenes that probably are related to the malignant potential of the lesions. Web site: http://www.delphion.com/details?pn=US05556871__

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Method of treating keratosis and compositions useful therefor Inventor(s): Bernstein; Joel E. (Deerfield, IL) Assignee(s): Jaye-boern Laboratories, Inc. (northbrook, Il) Patent Number: 4,588,590 Date filed: January 23, 1984 Abstract: The present invention includes an improved method of treating keratosis comprising periodically applying to the affected area a nail polish composition containing an effective amount of at least one corrosive agent for relieving the keratosis; also nail polish compositions are disclosed for use in the method. Excerpt(s): This invention generally relates to an improved method of treating keratosis and is particularly directed to novel nail polish compositions for use in such improved method. Keratosis is generally used to describe any disease of the skin characterized by an overgrowth of the epithelium. In particular, these diseases include what are commonly referred to as warts, corns and calluses. Warts are small intraepidermal growths of the skin caused by human papilloma virus and appear in children and young adults on the hands, face and feet. Corns are sharply demarcated hyperkeratotic lesions with a central core which are observed almost exclusively on the feet. Calluses are also hyperkeratotic lesions but have no central core and have a more diffuse outline. Calluses appear on the feet and hands where they may cause pain and discomfort. Treatment of keratosis includes the use of drugs with sufficient corrosive activity so as to cause peeling of the hyperkeratotic lesion. Topical corrosive agents used in the treatment of keratosis incude ascorbic acid, glacial acetic acid, lactic acid, salicylic acid, trichloroacetic acid, calcium pantothenate, zinc chloride, and podophyllum resin. Web site: http://www.delphion.com/details?pn=US04588590__

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Method of treating skin disorders with high-strength tretinoin Inventor(s): Kligman; Albert M. (151 E. Tenth Ave., Philadelphia, PA 19428), Kligman; Douglas E. (151 E. Tenth Ave., Philadelphia, PA 19428) Assignee(s): None Reported Patent Number: 6,008,254 Date filed: May 1, 1998 Abstract: Various skin disorders, excluding acne are treated by topical application to the skin of a tretinoin-containing composition including tretinoin in a dermatologically acceptable vehicle at such a concentration and applied in such a way as to induce desquamation of the skin to ameliorate the disorder. Preferably the compositions contain greater than 0.1 weight percent tretinoin, and more preferably at least 0.2 weight percent. The vehicle is preferably a solvent for the tretinoin, such as an alcohol/glycol or hydroalcoholic vehicle, but it is also possible to apply the tretinoin in a non-solvent vehicle such as emulsifying or suspending the tretinoin in a cream, dressing, gel, ointment or liquid polymer. The treatment achieves rapid amelioration of skin disorders such as photodamaged skin, hyperpigmentation, rosacea, premalignant cancers, wrinkles, superficial scarring, epidermal atrophy and atypia, and keratosis pilaris by daily or every other day application for about one to two months. Thereafter, the high strength applications may be tapered and the treated skin maintained with more conventional lower concentration compositions.

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Excerpt(s): The invention is directed to the treatment of various skin disorders with high-strength tretinoin (also known as vitamin A acid or all-trans retinoic acid). More particularly, the invention is directed to the treatment of skin disorders, especially of human facial skin, with amounts of tretinoin sufficient to induce desquamation of the skin to ameliorate the disorder. Caucasians who have had a good deal of sun exposure in childhood will show the following gross cutaneous alternations in adult life: wrinkling, leatheriness, yellowing, looseness, roughness, dryness, mottling (hyperpigmentation) and various premalignant growths (often subclinical). These changes are most prominent in light-skinned persons who burn easily and tan poorly. The baleful effects of sunlight are cumulative, increasing with time and often referred to as "photoaging". Although the anatomic degradation of the skin is most advanced in the elderly, the destructive effects of excessive sun exposure are already evident by the second decade. Serious microscopic alterations of the epidermis and dermis occur decades before these become clinically visible. Wrinkling, yellowing, leatheriness, loss of elasticity are very late changes. Retinoids (e.g., Vitamin A and its derivatives) are substances which are known to have a broad spectrum of biological activity. More specifically, these substances affect cell growth, differentiation and proliferation. Retinoids affect the differentiation, maintenance, and proliferation of many types of cells whether they are of ectodermal, endodermal or mesodermal origin; whether they are epithelial, fibroblastic or mesenchymal; or whether they are neoplastic, preneoplastic or non-neoplastic. Retinoids have found clinical utility in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Possible uses of retinoids are being explored in the prophylaxis and treatment of cancer. For a recent review of developments in the uses of retinoids, see Orfanos et al., "Current Use and Future Potential Role of Retinoids in Dermatology," Drugs 53:358-380 (March 1997). Web site: http://www.delphion.com/details?pn=US06008254__ •

Retinoic acid-containing polyether-polyurethane compositions Inventor(s): Goodman; Harris (San Francisco, CA), Quigley, Jr.; John W. (Foster City, CA) Assignee(s): Penederm, Inc. (foster City, Ca) Patent Number: 5,650,171 Date filed: April 29, 1992 Abstract: Novel retinoic acid-containing topical compositions in the form of creams, lotions, gels, and the like, are disclosed. These compositions contain a urethane compound having a molecular weight of up to about 60,000, prepared by reacting approximately two moles of a hydroxy-terminated linear alkylene or polyalkylene glycol with approximately one mole of a monomeric organic diisocyanate. The presence of the urethane compound leads to decreased percutaneous transmission of the retinoic acid, resulting in reduced skin irritation but undiminished therapeutic effectiveness of the retinoic acid when compared to retinoic acid-containing topical formulations otherwise identical except for the absence of a urethane compound. The compositions of this invention can be used to treat acne vulgaris and ameliorate photoaging of the skin, to retard and reverse the effects of senile keratosis, and to treat a variety of other skin conditions, such as hyperpigmentation and psoriasis, hitherto considered unsuitable for treatment with retinoic acid. Excerpt(s): This invention relates to retinoic acid-containing compositions. More particularly, this invention relates to retinoic acid-containing topical compositions for

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use in treating, inter alia, acne vulgaris in humans. The compositions of this invention exhibit reduced skin irritation but undiminished effectiveness as compared to prior art retinoic acid-containing topical compositions. Retinoic acid and like compounds are keratolytic agents, and have been used topically in the treatment of acne vulgaris; see, for example, Kligman U.S. Pat. No. 3,729,568 and Marks U.S. Pat. No. 4,247,547, issued Apr. 24, 1973 and Jan. 27, 1981, respectively. Retinoic acid and compositions containing it have also been used topically to retard and ameliorate photoageing of skin, especially facial skin, and to retard and reverse the effects of senile keratosis; see, for example, Kligman U.S. Pat. No. 4,603,146, issued Jul. 29, 1986. Web site: http://www.delphion.com/details?pn=US05650171__ •

Therapeutic agents for respiratory diseases Inventor(s): Hiki; Masato (Osaka, JP), Tanaka; Masaya (Kobe, JP) Assignee(s): Medion Research Laboratories (hyogo, Jp) Patent Number: 6,309,674 Date filed: November 19, 1999 Abstract: Prophylactic or therapeutic agents for respiratory diseases, allergic diseases, keratosis, and carcinomatous pain, containing Smilax china or a plant analogous thereto as the active ingredient. These agents can improve the condition and predisposition of acute and chronic respiratory diseases, such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, pan bronchiolitis and bronchiectasis, allergic diseases, such as atopic dermatitis, pollinosis, allergic rhinitis and allergic conjunctivitis, and keratosis, such as psoriasis, lichen, ichthyosis, furfur, and palmoplantar keratosis without side effects and at the same time can lower serum IgE level on an abnormally high level in a short period of time. After the symptom and predisposition have been improved, these agents can, even after suspension of administration, persistently lower the serum IgE level and in addition can inhibit the recurrence of the symptom. Excerpt(s): This application is a 371 of PCT/JP98/02237, filed May 21, 1998. The therapeutic agent for respiratory disease according to this invention relates to a prophylactic or therapeutic drug for respiratory diseases, a prophylactic or therapeutic drug for allergic diseases, a prophylactic or therapeutic drug for keratosis, a prophylactic or therapeutic drug for carcinomatous pain, a health food, a performance food, a cosmetic additive and a cosmetic product, which are capable of improving the symptom of, and the predisposition to, acute and chronic respiratory diseases, such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, pan bronchiolitis and bronchiectasis, allergic diseases, such as atopic dermatitis, pollinosis, allergic rhinitis and allergic conjunctivitis, and keratosis, such as psoriasis, lichen, ichthyosis, furfur, and palmoplantar keratosis without side effects and at the same time capable of lowering serum IgE level on an abnormally high level in a short period of time. After the symptom and predisposition have been improved, these agents can, even after suspension of administration, persistently lower the serum IgE level if it is still abnormally high and in addition can inhibit the recurrence of the symptom. Acute and chronic respiratory diseases such as acute bronchitis, bronchial asthma, asthmatic bronchitis, chronic bronchitis, diffuse ordinary bronchiolitis and bronchiectasis are intractable diseases. The therapy of these diseases is generally a symptomatic treatment centered around temporary control of coughing with an antitussive or, in case respiratory distress intervenes, assisted respiration with a bronchodilator, although the treatment is not rewarding in cases of severe coughing. Moreover, bronchial asthma can

Patents 89

be regarded as allergy and anti-allergics are also used for its prevention or therapy but the efficacy of such medication is not always reliable but even in patients with remission of the symptom, suspension of the administration results in recurrence of the symptoms. Adrenocortical hormones are administered in severe cases but, despite a certain rewarding effect they provide, sometimes cause intense side effects. Moreover, those, too, are symptomatic remedies. Thus, no drug is known of which recurrence of the symptom does not occur after suspension of administration. Health foods, for instance, are also available with claims to the effect that their intake leads to improvements in the patient's predisposition and a cure of diseases or control of symptoms but their efficacy is either not steadfast or has not been medically proven. Web site: http://www.delphion.com/details?pn=US06309674__ •

Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs Inventor(s): Asculai; Samuel Simon (Toronto, CA), Falk; Rudolf Edgar (Toronto, CA) Assignee(s): Hyal Pharmaceutical Corporation (mississauga, Ca) Patent Number: 5,639,738 Date filed: February 21, 1992 Abstract: A method of treating a mammal for a condition of the skin or exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratosis is provided. The method consists essentially of topically administering to the site of the condition, more than once per day over a period of days sufficient to treat the condition, a non-toxic effective dosage amount of a composition consisting essentially of(a) a nonsteroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis,(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the condition. The concentration of the hyaluronic add or salt thereof is between 1-3% by weight of the composition. The molecular weight of the hyaluronic acid or salt thereof is between 150,000 and 750,000 Daltons. A pharmaceutical excipient suitable for topical application is included. The NSAID in the composition may be diclofenac sodium. Excerpt(s): This invention also relates to formulations suitable for use in such treatments, the use of such formulations in such treatments, methods of such treatment, and the delivery of drugs for such treatments. Basal cell carcinoma is presently treated by surgery. Each lesion, together with all surrounding and underlying tissue (dermis, epidermis, and subdermis), is cut out. In some instances, surgery, while necessary for the patient's welfare, may put the patient at risk in some other respect (for example, a lesion on a patient's temple whose removal (resection) may jeopardize the patient's health). Squamous cell tumours are also treated the same way as are other forms of cancer in the skin and exposed tissue. Furthermore, other conditions and diseases of the skin and exposed tissue are treated the same way or in ways that cause discomfort to the patient, for example melanoma, genital warts, cervical cancer, HPV (Human Papilloma Virus). Actinic keratoses lesion is dealt with similarly. Additionally, liquid nitrogen has been used to remove the lesion. Web site: http://www.delphion.com/details?pn=US05639738__

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Treatment of hyperhidrosis, ichthyosis and wrinkling Inventor(s): Thornfeldt; Carl R. (1054 NW. 2nd Ave., Ontario, OR 97914) Assignee(s): None Reported Patent Number: 4,885,282 Date filed: March 8, 1988 Abstract: Skin suffering from emotional hyperhidrosis, ichthyosis with or without keratosis, and intrinsic or photoaging wrinkling is treated with mono- or discarboxylic acids containing 4 to 18 carbon atoms, or certain mercapto derivatives, salts or esters thereof. Excerpt(s): This invention relates to the treatment of hyperhidrosis, ichthyosis, and wrinkling of the skin. In particular, this invention is directed toward conditions involving hyperactivity of the adnexa and the epidermis, excessive cellular aggregation within the epidermis and stratum corneum, and photoaging or dermatoheliosis. The present invention resides in the discovery that certain mono- and dicarboxylic acids and their esters are effective in the treatment of these conditions, and represents a departure from the types of skin conditions on which such acids have previously been effective. U.S. Pat. Nos. 4,292,326 (Nazarro-Porro, Sept. 29, 1981) and 4,386,104 (Nazarro-Porro, May 31, 1983) disclose the use of dicarboxylic acids in the treatment of acne and melanocytic hyperpigmentary dermatoses. Web site: http://www.delphion.com/details?pn=US04885282__

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Treatment of osteocarcinoma with alpha-1--antitrypsin or secretory leucocyte protease inhibitor Inventor(s): Kronis; K. Anne (Tampa, FL), Lezdey; Darren (Indian Rocks Beach, FL), Lezdey; John (Indian Rocks Beach, FL) Assignee(s): Alpha Med Pharmaceuticals Corp. (clearwater, Fl) Patent Number: 6,670,325 Date filed: October 19, 2001 Abstract: The present invention relates to the treatment of cancerous conditions in mammals by the administration to the site of disease compositions containing serine protease inhibitor. The cancerous conditions include osteocarcinomas, melanoma, Karopsi sarcoma and keratosis. The compositions are also useful to relieve the pain associated with the disease. Excerpt(s): The present invention relates to the treatment of cancer and to the pain associated with cancer. The compositions utilized consist of protease inhibitors which prevent the proliferation of cancer cells and bind with the protease released by the cancer cells. Viruses such as human papilloma viruses can lead to cancer, such as cervical cancer. Matrix metalloproteases especially metallo-elastase have been found to be involved in lung cancer as well as skin cancer. Web site: http://www.delphion.com/details?pn=US06670325__

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Treatment of palmar and plant disturbed keratosis Inventor(s): Van Scott; Eugene J. (1138 Sewell Lane, Rydal, PA 19046), Yu; Ruey J. (4400 Dexter St., Philadelphia, PA 19128) Assignee(s): None Reported Patent Number: 3,988,470 Date filed: March 7, 1975 Abstract: A treatment to alleviate the symptoms of diseases characterized by defects in keratinization consisting of the topical application of an ointment or lotion containing one or more lower aliphatic compounds having from two to about six carbon atoms, and preferably having.alpha.-carbon functionality is disclosed. The compounds include.alpha.-hydroxy acids, keto acids and esters thereof, and 3-hydroxybutyric acid. The therapeutic composition may include one or more of the compounds present in a total amount of from one to twenty percent in either a water or alcohol solution or an ointment. Topical application to affected areas has been found to achieve a complete remission of dandruff, acne and palmar and plantar hyperkeratosis. Excerpt(s): This invention relates to a treatment for diseases characterized by defective keratinization including dandruff, acne and palmar and plantar hyperkeratosis, and specifically to compounds which have been found to be effective when topically applied, to heal the skin lesions associated with these diseases in humans. Disease conditions characterized by defects in keratinization are relatively common and many different treatments have been prescribed in the past with varying degrees of effectiveness. In each of these disease conditions the process whereby the epidermal cells mature and form a surface layer (stratum corneum) is defective. Therefore, the signs and symptoms of diseases associated with defective keratinization are an overproduction of cells and/or their retention in the stratum corneum for abnormally prolonged periods. In our parent application Ser. No. 394,269 filed Sept. 9, 1973 and entitled TREATMENT OF ICHTHYOSIFORM DERMATOSES a treatment was described for ichthyosis, a fish-scale-like appearance of the human skin. Ichthyosiform dermatoses are hereditary disorders characterized by excessive amounts of scale which accumulate on the skin surface. Web site: http://www.delphion.com/details?pn=US03988470__

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Viscous compositions containing carbon dioxide Inventor(s): Hiki; Masato (Osaka, JP), Tanaka; Masaya (Kobe, JP) Assignee(s): Medion Research Laboratories Inc. (kobe, Jp) Patent Number: 6,689,339 Date filed: August 17, 2000 Abstract: A carbon dioxide-containing viscous composition wherein carbon dioxide bubbles are retained in an aqueous viscous composition. Use of the composition makes it possible to treat or ameliorate itching accompanying mucocutaneous diseases or mucocutaneous disorders, mucocutaneous injury, dental diseases, skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders, musculoskeletal diseases, nervous system diseases, keratosis, constipation, unwanted hair re-growing after depilation, cosmetic troubles in the skin or hair, partial obesity, etc. while exerting little side effects.

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Excerpt(s): Thee present invention relates to a carbon dioxide-containing viscous composition which is capable of treating or ameliorating itching accompanying mucocutaneous diseases or mucocutaneous disorders such as athlete's foot, insect bite, atopic dermatitis, nummular eczema, xeroderma, seborrheic eczema, urticaria, prurigo, housewives' eczema, acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma, psoriasis, ichthyosis, palmoplantar keratoderma, lichen, pityriasis, wound, burn, rhagades, erosion and chilblain; mucocutaneous injuries such as decubitus ulcer, wound, burn, angular stomatitis, stomatitis, skin ulcer, rhagades, erosion, chilblain and gangrene; incomplete takes of skin graft, skin flap, etc.; dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, nigricans gingiva, stomatitis; skin ulcer, cryesthesia and numbness caused by peripheral circulatory disorders such as thromboangitis obliterans, arteriolosclerosis obliterans, diabetic peripheral circulatory disorder and varicosis in lower extremity; musculoskeletal diseases such as chronic rheumatoid arthritis, cervico-omo-brachial syndrome, myalgia, arthralgia and lumbago; nervous system diseases such as neuralgia, polyarthritis and subcute myelo-optic neuropathy; keratoses such as psoriasis, corn, callosity, ichthyosis, palmoplantar keratoderma, lichen and pityriasis; suppurative dermopathies such as acne vulgaris, impetigo, folliculitis, carbuncle, furunculosis, phlegmon, pyoderma and suppurative eczema; constipation caused by loss of reflection of defecation; suppression of hair re-growth after depilation (treatment of unwanted hair); cosmetic troubles in the skin or hair such as freckles, rough skin, muddy complexion, faded skin complexion and loss of hair glossiness, etc. with little side effects as well as of slimming a desired part of the body, and to prophylactic and therapeutic methods using the composition. Antihistamines and antiallergics for external application are typically used in a topical therapy for itching. Such drugs are used when itching occurs and work to suppress the itching temporarily to a certain degree. Itching associated with eczema is generally treated with non-steroidal anti-inflammatory drugs or steroidal drugs for external application which prevent the itching by suppressing inflammation. However, the antihistamines and antiallergics for external application are barely effective in treating itching accompanying atopic dermatitis, athlete's foot and insect bite. The non-steroidal anti-inflammatory drugs and steroidal drugs for external application do not effect satisfactorily nor immediately on itching. Further, the steroidal drugs are difficult to use because of the serious side effects. Web site: http://www.delphion.com/details?pn=US06689339__

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

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

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Anti-cancer compositions Inventor(s): Kronis, K. Anne; (Tampa, FL), Lezdey, Darren; (Indian Rocks Beach, FL), Lezdey, John; (Indian Rocks Beach, FL) Correspondence: John Lezdey; John Lezdey & Associates; 4625 East Bay Drive; Clearwater; FL; 33764; US Patent Application Number: 20030077266 Date filed: October 19, 2001 Abstract: The present invention relates to the treatment of cancerous conditions in mammals by the administration to the site of disease compositions containing serine protease inhibitor. The cancerous conditions include osteocarcinomas, melanoma, Karopsi sarcoma and keratosis. The compositions are also useful to relieve the pain associated with the disease. Excerpt(s): The present invention relates to the treatment of cancer and to the pain associated with cancer. The compositions utilized consist of protease inhibitors which prevent the proliferation of cancer cells and bind with the protease released by the cancer cells. Viruses such as human papilloma viruses can lead to cancer, such as cervical cancer. Matrix metalloproteases especially metallo-elastase have been found to be involved in lung cancer as well as skin cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Curcumin and curcuminoid inhibition of angiogenesis Inventor(s): Arbiser, Jack L.; (Atlanta, GA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20010025034 Date filed: January 18, 2001 Abstract: Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It has further been discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF. Representative skin disorders to be treated include the malignant diseases angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and the nonmalignant diseases or conditions including psoriasis, lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis. Excerpt(s): The invention is generally in the field of methods of inhibiting angiogenesis, and more specifically is drawn to methods and compositions for inhibiting angiogenesis. Current treatments of cancer and related diseases have limited effectiveness and numerous serious unintended effects. Based primarily on chemical,

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radiation and surgical therapy, these treatments have progressed only incrementally during more than thirty years of intensive research to discover the origins and devise improved therapies of neoplastic diseases. Current research strategies emphasize the search for effective therapeutic modes with less risk, including the use of natural products and biological agents. This change in emphasis has been stimulated by the fact that many of the consequences, to patients and their offspring, of conventional cancer treatment, including new cancers, mutations and congenital defects, result from their actions on genetic material and mechanisms. Hong et al., J. Natl. Cancer Inst. Monogr. 17:49-53 (1995). Efforts continue to discover the origins of cancer at the genetic level, and correspondingly new treatments, but such interventions also may have serious unanticipated effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treating the pathological lesions of the skin that develop by ultraviolet radiation of the sunlight Inventor(s): Farkas, Bea; (Szeged, HU), Nagy, Peter Literati; (Budapest, HU), Vadasz, Agnes; (Budapest, HU), Vigh, Laszlo; (Szeged, HU) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20020131938 Date filed: December 7, 2001 Abstract: The invention relates to methods for prevention and/or treatment of skin lesions caused by exposure to ultraviolet radiation. Exemplary condition that can be prevented or treated are actinic keratosis, dry skin,polymorphic light exanthema, photopathology, photo-allergy, solar atrophy, stria migrans, elastoma diffusum, X-ray dermatits, gouty polychondritis and decubitis ulcer. The method employs application to the skin of a composition comprising a hydroximic acid derivative of the formula 1 Excerpt(s): The invention refers to a method for treating the pathological lesions of the skin that normally develop due to the ultraviolet (UV) radiation of the sunlight. Exposure of human skin to sunlight has several known unpleasant effects such as sunburn and pathological lesions leading to carcinogenesis. Due to the ultraviolet radiation of sunlight, free radicals (e.g. hydroxy radicals or nascent oxygen) form in the skin. Such free radicals can injure the DNA of skin cells and contribute to photoaging of the skin. Photoaging is characterized by clinical, histological and biochemical changes which differ from alterations in chronologically aged but sunprotected skin [Herschenfeld, R. E. et al.: The cumulative effect of ultraviolet radiation on the skin photoaging, in Photodermatology, Hawk, J. L. M. , Ed., Arnold, London, Sydney, Oakland, 1999, 89-102]. Photoaging includes changes attributable to chronic sun exposure and results in dry skin, wrinkling, laxity or even a variety of benign neoplasms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating actinic keratosis Inventor(s): Bhagwat, Dileep; (Bronxville, NY), Glassman, Bradley P.; (Fairfield, NJ), Glassman, Daniel; (Fairfield, NJ) Correspondence: Covington & Burling; Attn: Patent Docketing; 1201 Pennsylvania Avenue, N.W.; Washington; DC; 20004-2401; US Patent Application Number: 20030212127 Date filed: May 9, 2002 Abstract: Described is a novel approach for treating actinic keratosis which involves the use of urea in a dermatological composition. The urea composition can be included in pre-treatment, treatment and post-treatment steps. Also described are novel topical compositions for the treatment step containing a combination of urea and a pharmaceutical agent for treating actinic keratosis, such as a caustic agent, 5fluorouracil or a photosensitizing agent. Excerpt(s): The present invention relates to an improved method of treating actinic keratosis. This invention changes the focus of treating actinic keratosis from a singular event to a comprehensive procedure, which includes the use of a composition containing urea as a principal component and can include pre-treatment, treatment and post-treatment. Treatment may involve concurrent or non-concurrent topical applications. Actinic Keratoses (AKs) are very common, precancerous lesions that arise on photodamaged skin. Extensive sun exposure and skin type are the most important factors in their development. The term actinic means that development of the lesions results from exposure to ultraviolet (UV) radiation, the primary source of which is sunlight. Keratosis is a general term for skin lesions characterized by overgrowth and thickening of the stratum corneum. There is a strong correlation between sun exposure and the occurrence of AKs. Commonly affected sites are the balding scalp, forehead, face, ears, neck, and back of the forearms and hands. Although most AKs develop on the head and upper extremities, they can also occur on the legs or anywhere where there has been excessive exposure to UV radiation. Also, the lesions can develop as a result of UV light exposure from artificial sources, such as tanning booths. Medical radiation exposure or exposure through occupational means may also cause AKs. After several years, a small percentage of AKs degenerate to squamous cell carcinomas. Thus, the lesions require careful evaluation and effective treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treatment for dermatological disorders and compositions therefor Inventor(s): Levy, Sharon F.; (Philadelphia, PA), Tobey, Raymond E.; (Radnor, PA) Correspondence: Aventis Pharmaceuticals, INC.; Patents Department; Route 202-206, P.O. Box 6800; Bridgewater; NJ; 08807-0800; US Patent Application Number: 20020009497 Date filed: December 20, 2000 Abstract: A composition and method of treatment of dermatological disorders using 5fluorouracil at levels below about 1.0%. The disorders to be treated include actinic keratosis, non-malignant lesions of the skin and psoriasis. Excerpt(s): This application is a continuation of PCT/US99/14354, filed Jun. 24, 1999, which claims priority from U.S. Provisional Patent Application No. 60/090,892, filed

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Jun. 26, 1998. The present invention relates to a novel method of treatment of dermatological disorders such as actinic or solar keratoses using low levels of 5Fluorouracil and compositions therefor. Actinic keratosis is a type of epithelial precancerous lesion. Sun exposure for many years and poor pigmentation of the skin (i.e., light-colored skin) predispose one to developing actinic keratosis. Actinic keratosis has been treated in various ways, including cryosurgery, ionizing radiation in the form of X-rays, and topical chemotherapy such as that using fluorouracil or trichloroacetic acid. Actinic keratosis is sometimes referred to as solar keratosis or senile keratosis. Actinic keratosis is considered by some as a form of carcinoma in situ; actinic keratosis may progress to overt squamous cell carcinoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for increasing skin remodeling Inventor(s): Pickart, Loren R.; (Bellevue, WA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030166510 Date filed: October 11, 2001 Abstract: Skin remodeling is stimulated at the site of blemished skin using an ionic metal-peptide complex to diminish or remove the skin imperfection. The blemish can be a scar, especially surgical or wound scars, acne scars, keloid scars, and the like, or a skin tag, callus, benign skin mole, stretch marks, facial keratosis, thickened sunspots of the skin, or a vitiligo spot. The peptide-ionic metal complex is comprised of an ionic metal selected from copper(II), tin(II), tin(IV), and zinc(II), and salts thereof, and the peptide component can be a hydrolysis of casein, collagen, elastin, meat products, silk protein, or soybean protein, or a chemically synthesized dipeptide, tripeptide, tetrapeptide or the like which complexes with the ionic metal. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/239,831, filed Oct. 11, 2000, incorporated herein by reference in its entirety. The treatment of skin imperfections such as scars, solar keratosis (sun damages marks), age spots, vitiligo marks, skin tags, calluses, keloids, moles, pigmentations, and stretch marks remains a major problem despite the development of numerous treatments such as the use of silicone sheets, scar subcision, deep chemical peels, laser resurfacing, dermabrasion and so forth. The problem with current techniques for removal of skin imperfections is that they all are poorly effective, expensive and often painful. And, if the dermatologist or esthetician performing the procedure is not highly skilled, the results can produce further scarring. One way to accelerate remodeling is the use of exfoliating chemicals to speed skin shedding; in stronger versions they are used as "chemical peels". Likewise, biochemicals such as retinol and retinoic acid activate systems that increase skin breakdown and resynthesis. Another way to accelerate skin remodeling is with the use of skin regeneration accelerators that enhance the skin's production of collagen and elastin. The use of skin regeneration accelerators can be combined with the methods that cause controlled skin damage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical formulation comprising an immune response modifier Inventor(s): Busch, Terri F.; (St. Paul, MN), Fretland, Mary; (Eagan, MN), Gust-Heiting, Amy L.; (Hudson, WI), Scholz, Matthew T.; (Woodbury, MN), Skwierczynski, Raymond D.; (Oakdale, MN) Correspondence: Attention: Dean A. Ersfeld; Office OF Intellectual Property Counsel; 3M Innovative Properties Company; P.O. Box 33427; ST. Paul; MN; 55133-3427; US Patent Application Number: 20030199538 Date filed: November 27, 2002 Abstract: Pharmaceutical formulations comprising an immune response modifier (IRM) chosen from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazolo-quinolineamines, oxazolo-quinolinamines, thiazolopyridinamines, oxazolo-pyridinamines, imidazonaphthyridine amines, tetrahydroimidazonaphthyridine amines, and thiazolonaphthyridine amines; a fatty acid; and a hydrophobic, aprotic component miscible with the fatty acid are useful for the treatment of dermal associated conditions. Novel topical formulations are provided. In one embodiment, the topical formulations are advantageous for treatment of actinic keratosis, postsurgical scars, basal cell carcinoma, atopic dermatitis, and warts. Excerpt(s): This application claims priority to Provisional Patent Application Serial No. 60/340,605, filed Nov. 29, 2001 and Provisional Patent Application Serial No. 60/378,452, filed May 6, 2002. The present invention is directed to pharmaceutical formulations comprising at least one immune response modifier chosen from imidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazoloquinoline amines, oxazoloquinoline amines, thiazolopyridine amines, oxazolopyridine amines, imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines. Embodiments of the present invention are directed to topical formulations for application to the skin of a mammal. Other embodiments of the present invention are directed to methods for treating dermal diseases. Many imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazoloquinoline amine, oxazoloquinoline amine, thiazolopyridine amine, oxazolopyridine amine, imidazonaphthyridine amine, imidazotetrahydronaphthyridine amine, and thiazolonaphthyridine amine compounds have demonstrated potent immunostimulating, antiviral and antitumor (including anticancer) activity, and have also been shown to be useful as vaccine adjuvants. These compounds are hereinafter collectively referred to as "IRM" (immune response modifier) compounds. One of these IRM compounds, known as imiquimod, has been commercialized in a topical formulation, Aldara.TM., for the treatment of anogenital warts associated with human papillomavirus. 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 keratosis, you can access the U.S. Patent Office archive via the Internet at the following Web address:

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

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “keratosis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on keratosis: •

Diseases of the Oral Mucosa and the Lips Source: Orlando, FL: W.B. Saunders Company. 1993. 389 p. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This book is a clinically oriented atlas and text covering the symptoms and diseases of the oral mucosa and perioral skin. The authors focus on the essential aspects of each illness, concentrating on the clinical features that are important in the differential diagnosis. The authors include not only diseases confined to the oral mucosa but also those oral problems that may be signs of accompanying cutaneous (skin) or systemic diseases. Sixty-seven chapters are presented in three sections: the normal oral mucosa, general aspects of oral pathology, and diseases of the oral mucosa and the lips. Specific

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topics are inflammation of the lips, acquired diseases of the tongue, gingival hyperplasia, enlargement of the parotid gland, aphthous ulcers (stomatitis), pyostomatitis vegetans, disorders of pigmentation, urticaria and angioedema, psoriasis, Reiter's syndrome, lichen planus, graft-versus-host disease, rosacea, perioral dermatitis, erythema multiforme, acute febrile neutrophilic dermatosis (Sweet's syndrome), vesicular and bullous autoimmune diseases, desquamative gingivitis, necrotizing sialometaplasia, oral mucosal hemorrhage, viral diseases, bacterial diseases, fungal diseases, protozoal and parasitic diseases, mechanical damage, trauma, allergic and toxic contact stomatitis, occupational diseases of the oral mucosa, drug reactions and side effects, morphea and scleroderma, lichen sclerosus et atrophicus, dermatomyositis, lupus erythematosus, Sjogren's syndrome, polyarteritis nodosa, giant cell arteritis, plasma cell gingivitis, oral submucous fibrosis, halitosis, xerostomia, sialorrhea, selfinduced mucosal injuries, benign granulomatous processes, malignant granulomatoses, heterotopias and congenital malformations, genodermatoses and congenital syndromes, benign and malignant tumors, actinic keratosis, leukoplakia, paraneoplastic disorders, and oral signs of hematologic, nutritional, metabolic, and endocrine disorders. Each chapter includes full-color photographs and references are provided in individual sections. A subject index concludes the volume. (AA-M). •

Tongue Complaints Source: in Scully, C. Handbook of Oral Disease: Diagnosis and Management. New York, NY: Thieme New York. 2001. p.356-384. Contact: Available from Thieme New York. 333 Seventh Avenue, New York, NY 10001. (212) 760-0888, ext 110. PRICE: $35.00 plus shipping and handling. ISBN: 1841840874. Summary: This chapter on tongue complaints is from a handbook of oral disease that is intended to be used by all members of the dental team who need a ready office reference. The handbook covers the more common and important soft tissue orofacial disorders and gives clinically relevant aspects of the etiology, diagnosis, treatment, and prevention. This chapter covers amyloidosis, ankyloglossia (tongue tie), black hairy tongue, candidal glossitis (associated with fungal infection, thrush), coated tongue (white hairy tongue), deficiency glossitis, eosinophilic ulcer, erythema migrans (geographic tongue), fissured tongue, foliate papillitis, granular cell tumor, hairy leukoplakia, lingual thyroid, median rhomboid glossitis, oral-facial-digital syndrome, sublingual (under the tongue) keratosis, swelling, and syphilitic leukoplakia. For each condition, the authors note etiology (cause), diagnosis, symptoms, epidemiology, risk factors, treatment, and prevention (where possible). Much of the information is provided in table or outline format for ease of reference. Full color photographs illustrate some conditions. 39 figures. 9 references.

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 “keratosis” (or synonyms) into the search box, and select “books only.”

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From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Porokeratosis Mibelli-Respighi: an analysis with particular regard on [sic] the histological changes in the initial manifestations. Author: Kúta, Adolf; Year: 1965

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

Chapter 54: Darier-White Disease (Keratosis Follicularis) and Acrokeratosis Verruciformis Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 614-619. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail: [email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with an overview of Darier-White Disease (DWD), an autosomal dominant disorder with altered keratinization of the epidermis, nails, and mucous membranes, and acrokeratosis verruciformis, which is a rare, autosomal dominant disorder appearing at birth or early childhood. The chapter discusses DWD in terms of its etiology, pathogenesis, clinical manifestations, pathology, differential diagnosis, and treatment. DWD, which usually beings in the first or second decade of life and affects both sexes equally, usually occurs on the face, forehead, scalp, chest, and back. DWD is characterized by multiple discrete, scaling, rough, crusted, pruritic skin papules that are frequently malodorous and disfiguring. Pathological features include premature and abnormal keratinization and loss of epidermal adhesion with acantholysis, as well as the presence of eosinophilic dyskeratotic cells in the spinous layer and in the stratum corneum. DWD may be confused with seborrheic dermatitis. Other conditions that must be considered in the diagnosis include familial pemphigus and pemphigus foliaceous. Treatment options include topical or systemic retinoids, surgery, and antibiotics. The chapter also discusses acrokeratosis verruciformis in terms of its clinical manifestations, pathology, differential diagnosis,

11

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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treatment, and course. The lesions of the disease are small, verrucous, flat papules that appear mainly on the dorsa of the hands and feet. Conditions similar to acrokeratosis verruciformis include DWD, epidermodysplasia verruciformis, veruca plana, and hard nevus of Unna. The only effective treatment is superficial destruction. 11 figures and 50 references.

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

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

3M files to market Aldara cream for actinic keratosis Source: Reuters Industry Breifing Date: May 05, 2003

•

Melanoma can clinically mimic seborrheic keratosis Source: Reuters Medical News Date: December 30, 2002

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•

Berlex Laboratories licenses rights to actinic keratosis treatment Source: Reuters Medical News Date: November 24, 1999

•

DUSA gets FDA approvable letter for actinic keratosis treatment Source: Reuters Medical News Date: June 30, 1999 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 “keratosis” (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 “keratosis” (or synonyms). If you know the name of a company that is relevant to keratosis, 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 “keratosis” (or synonyms).

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

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

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

Topical - U.S. Brands: Solaraze http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500247.html

Isotretinoin •

Systemic - U.S. Brands: Accutane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202309.html

Tretinoin •

Topical - U.S. Brands: Avita; Renova; Retin-A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202574.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 Institute12: •

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

•

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

12

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

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•

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

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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.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

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

•

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

•

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

•

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

•

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

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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

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

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “keratosis” (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 15205 39 96 3 76 15419

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “keratosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

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

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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 Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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 Keratosis In the following section, we will discuss databases and references which relate to the Genome Project and keratosis. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21

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. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “keratosis” (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 keratosis: •

Alopecia Congenita with Keratosis Palmoplantaris Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104100

•

Keratosis Follicularis Spinulosa Decalvans Cum Ophiasi Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308800

•

Keratosis Follicularis, Dwarfism, and Cerebral Atrophy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308830

•

Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601952

•

Keratosis Palmaris Et Plantaris with Clinodactyly Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=148520

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Keratosis Palmoplantaris Papulosa Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=148600

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Keratosis Palmoplantaris Striata I Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=148700

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Keratosis Palmoplantaris Striata Iii Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607654

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Keratosis Pilaris Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604093

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Keratosis, Focal Palmoplantar and Gingival Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=148730

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Onychogryposis, Pedal, with Keratosis Plantaris and Coarse Hair Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164680

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Porokeratosis of Mibelli Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175800

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Porokeratosis Punctata Palmaris Et Plantaris Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175860 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,

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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

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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

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

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

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

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

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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

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

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

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

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

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

24

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

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

25

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

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

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Dermatitis http://www.nlm.nih.gov/medlineplus/dermatitis.html Eczema http://www.nlm.nih.gov/medlineplus/eczema.html Melanoma http://www.nlm.nih.gov/medlineplus/melanoma.html Skin Diseases http://www.nlm.nih.gov/medlineplus/skindiseases.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 keratosis. 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: •

Dry Skin and Keratosis Pilaris Source: Schaumberg, IL: American Academy of Dermatology. 2002. 6 p. Contact: Available from American Academy of Dermatology. 930 E. Woodfield Road, P.O. Box 4014, Schaumberg, IL 60168-4014. (888) 462-DERM ext. 22. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This brochure provides patients with information on dry skin and keratosis pilaris. Dry skin occurs when the skin lacks water and may be caused by a number of factors including aging, season, and climate. To prevent skin from becoming dry, patients should try taking brief baths or showers, avoiding hot water, using mild soaps, patting skin dry with a towel, moisturizing immediately after bathing, and using lubricating agents before shaving. Dry skin can sometimes lead to dermatitis, inflammation of the skin. Corticosteroids are usually prescribed to treat this condition. Keratosis pilaris is a common, benign, condition most commonly found in children and young adults and characterized by small bumps on the skin and a sandpapery texture. It is most often found on the upper arms, thighs, and cheeks. Lubricants are used to help with the dryness, and mild peeling agents are used to remove excess skin that blocks the hair follicles. The treatment is usually only temporary as the condition is hereditary. 5 figures.

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Actinic Keratosis Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 3 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail: [email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have an actinic keratosis with information on the symptoms and treatment of this skin condition. An actinic keratosis, a scaly or crusty bump that forms on the skin, ranges in size from a pinhead to an inch in diameter. A keratosis appears most often on sun exposed areas. Its presence indicates that sun damage has occurred. People who are at greatest risk for sunburn, and thus the possible development of actinic keratoses, are those who have fair skin; blonde or red hair; and blue, green, or gray eyes. An actinic keratosis is dangerous because it can be the first step in the development of skin cancer. The most aggressive form of keratosis, actinic cheilitis, appears on the lips and can progress to squamous cell carcinoma. Treatments for actinic keratosis include curettage, shave removal, cryosurgery, chemical peels, and 5-fluorouracil cream. 2 figures.

•

Actinic Keratosis: What You Should Know About This Common Precancer Source: New York, NY: Skin Cancer Foundation. 1998. 6 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet uses a question and answer format to provide the general public with information on actinic keratosis, a scaly or crusty bump that arises on the skin. Actinic keratosis is dangerous because its presence indicates that sun damage has occurred and that any kind of cancer can develop. The pamphlet presents examples of common forms of actinic keratoses in the locations where they most often develop. Keratoses located on the back of the hand, forehead, bald scalp, lower lip, cheek, and ear are depicted. The pamphlet explains how common actinic keratosis is, what causes it, and who is at greatest risk for developing it. In addition, the pamphlet briefly describes various surgical and pharmaceutical methods of eradicating actinic keratoses and offers suggestions on preventing them. 4 figures. The National Guideline Clearinghouse™

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

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AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2001 Mar-April; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2847&nbr=2073&a mp;string=keratosis

•

Diagnosis and treatment of otitis media in children Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 May (revised 2002 Dec); 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3667&nbr=2893&a mp;string=keratosis

•

Guidelines for referral to pediatric surgical specialists Source: American Academy of Pediatrics - Medical Specialty Society; 2002 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3420&nbr=2646&a mp;string=keratosis

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Hammertoe syndrome Source: Academy of Ambulatory Foot and Ankle Surgery - Medical Specialty Society; 2000 (revised 2003 Sep); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4242&nbr=3242&a mp;string=keratosis

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Metatarsalgia/intractable plantar keratosis/Tailor's bunion Source: Academy of Ambulatory Foot and Ankle Surgery - Medical Specialty Society; 2000 (revised 2003 Sep); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4246&nbr=3246&a mp;string=keratosis

•

Recommendations for using smallpox vaccine in a pre-event smallpox vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 February 26; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3623&nbr=2849&a mp;string=keratosis

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Skin cancer Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2001 July 28); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3814&nbr=3040&a mp;string=keratosis

•

Type 2 diabetes practice guidelines Source: International Diabetes Center - Private Nonprofit Organization; 2000 (revised 2003); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4159&nbr=3187&a mp;string=keratosis 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 keratosis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

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

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

•

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

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

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

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to keratosis. By consulting all of associations listed in

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

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

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

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

26

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

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

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

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

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

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

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

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

27

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on keratosis: •

Basic Guidelines for Keratosis Keratosis pilaris Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001462.htm

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Background Topics for Keratosis Benign Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002236.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm

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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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KERATOSIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [NIH]

Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinic keratosis: A precancerous condition of thick, scaly patches of skin. Also called solar or senile keratosis. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adherens Junctions: Anchoring points where the cytoskeleton of neighboring cells are connected to each other. They are composed of specialized areas of the plasma membrane where bundles of microfilaments attach to the membrane through the transmembrane linkers, cadherins, which in turn attach through their extracellular domains to cadherins in the neighboring cell membranes. In sheets of cells, they form into adhesion belts (zonula adherens) that go all the way around a cell. [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] Adnexa: The appendages of the eye, as the lacrimal apparatus, the eyelids, and the extraocular muscles. [NIH]

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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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [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-helix: One of the secondary element of protein. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of

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organic matter fossilized in amber. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] 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] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [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] 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] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of

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hemoglobin. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Angiosarcoma: A type of cancer that begins in the lining of 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anogenital: Pertaining to the anus and external genitals. [EU] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] 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]

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Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

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] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] 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] Areola: The area of dark-colored skin on the breast that surrounds the nipple. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH]

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Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] 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] 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] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] 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] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous

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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] 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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [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] Basilar Artery: The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. [NIH] Baths: The immersion or washing of the body or any of its parts in water or other medium for cleansing or medical treatment. It includes bathing for personal hygiene as well as for medical purposes with the addition of therapeutic agents, such as alkalines, antiseptics, oil, etc. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [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]

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Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bowen: Intraepithelial epithelioma affecting the skin and sometimes the mucous membranes. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH]

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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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Bunion: A swelling of the bursa mucosa of the ball of the great toe, with thickening of the overlying skin and forcing of the toe outward. [NIH] Cadherins: A group of functionally related glycoproteins responsible for the calciumdependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and Ncadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via a homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] 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] Carbuncle: An infection of cutaneous and subcutaneous tissue that consists of a cluster of boils. Commonly, the causative agent is Staphylococcus aureus. Carbuncles produce fever, leukocytosis, extreme pain, and prostration. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU]

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Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH]

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Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] 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 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] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemexfoliation: Application of a cauterant to the skin for the purpose of causing a superficial destruction of the epidermis and upper layers of the dermis. After healing, the treated area has new epithelium. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [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] 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] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all

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human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [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] 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] 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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU]

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

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Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]

fumarate.

Stimulant

proposed

as

Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]

Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to

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which a subject has learned to respond. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Curette: A spoon-shaped instrument with a sharp edge. [NIH] 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] 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] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defecation: The normal process of elimination of fecal material from the rectum. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH]

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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]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [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] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]

Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Dermo-epidermal: A patch of skin taken from the patient is directly grafted on the wound. [NIH]

Desmosomes: Attachment bodies between cells such as in the corneal epithelium, which possibly allow tonofibrils to pass from cell to cell and which can degenerate to allow cells to migrate to cover a denuded area. [NIH] Desquamation: The shedding of epithelial elements, chiefly of the skin, in scales or small sheets; exfoliation. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Diagnostic procedure: A method used to identify a disease. [NIH] Diaper Rash: A type of irritant dermatitis localized to the area in contact with a diaper and occurring most often as a reaction to prolonged contact with urine, feces, or retained soap or detergent. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] 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] Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] Difluoromethylornithine: DFMO. An anticancer drug that has been shown to reduce the risk of cancer in animals. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are

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the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [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] 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] 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] 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] 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] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dysplastic nevi: Atypical moles; moles whose appearance is different from that of common moles. Dysplastic nevi are generally larger than ordinary moles and have irregular and indistinct borders. Their color frequently is not uniform and ranges from pink to dark brown; they usually are flat, but parts may be raised above the skin surface. [NIH] Dysplastic nevus: An atypical mole; a mole whose appearance is different from that of a common mole. A dysplastic nevus is generally larger than an ordinary mole and has

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irregular and indistinct borders. Its color frequently is not uniform and ranges from pink to dark brown; it is usually flat, but parts may be raised above the skin surface. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ear Diseases: Diseases of the ear, general or unspecified. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eflornithine: 2-(Difluoromethyl)-DL-ornithine. An inhibitor of ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthetic pathway. As a result of this inhibition of polyamine synthesis, the compound is effective in preventing cancer formation in many organ systems, inhibiting cancer growth, and reducing tumor size. It also has synergistic action with other antineoplastic agents. In addition, it has been found effective as a trypanocidal agent. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous)

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production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] 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] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [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] Epidermodysplasia Verruciformis: An autosomal recessive trait with impaired cellmediated immunity. About 15 human papillomaviruses are implicated in associated infection, four of which lead to skin neoplasms. The disease begins in childhood with red papules and later spreads over the body as gray or yellow scales. [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epidermolysis Bullosa Acquisita: Form of epidermolysis bullosa characterized by trauma-

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induced, subepidermal blistering with no family history of the disease. Direct immunofluorescence shows IgG deposited at the dermo-epidermal junction. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelioma: A neoplasm of epithelial origin, ranging from benign (adenoma and papilloma) to malignant (carcinoma). [EU] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Infectiosum: Contagious infection with human B19 Parvovirus most commonly seen in school age children and characterized by fever, headache, and rashes of the face, trunk, and extremities. It is often confused with rubella. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] 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] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Exanthema: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional

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synonyms in current terminology. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] 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] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extraocular: External to or outside of the eye. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is

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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] 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] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Founder Effect: The principle that when a small subgroup of a larger population establishes itself as a separate and isolated entity, its gene pool carries only a fraction of the genetic diversity of the parental population. This may result in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive. [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] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Furunculosis: An infection where furuncles are present over a period of weeks to months. Species of Staphylococcus are usually the causative agents. [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and

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electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH] Gingival Recession: The exposure of root surface by an apical shift in the position of the gingiva. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH]

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Glossitis: Inflammation of the tongue. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] 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 cells against a person's tissue. [NIH] Granular Cell Tumor: Unusual tumor affecting any site of the body, but most often encountered in the head and neck. Considerable debate has surrounded the histogenesis of this neoplasm; however, it is considered to be a myoblastoma of, usually, a benign nature. It affects women more often than men. When it develops beneath the epidermis or mucous membrane, it can lead to proliferation of the squamous cells and mimic squamous cell carcinoma. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Halitosis: An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. [NIH] 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] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the

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prosthetic group in many hemeproteins. [NIH] Hemidesmosomes: An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] 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 Gestationis: An itching polymorphous bullous eruption which occurs in pregnancy or the puerperium and which recurs in successive pregnancies. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [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]

Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]

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Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [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] Hydroalcoholic: Of or relating to water and alcohol. [EU] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals. [NIH]

Hydroxylamine: A colorless inorganic compound (HONH2) used in organic synthesis and as a reducing agent, due to its ability to donate nitric oxide. [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] Hyperhidrosis: Excessive sweating. In the localized type, the most frequent sites are the palms, soles, axillae, inguinal folds, and the perineal area. Its chief cause is thought to be emotional. Generalized hyperhidrosis may be induced by a hot, humid environment, by fever, or by vigorous exercise. [NIH]

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Hyperkeratosis: 1. Hypertrophy of the corneous layer of the skin. 2a. Any of various conditions marked by hyperkeratosis. 2b. A disease of cattle marked by thickening and wringling of the hide and formation of papillary outgrowths on the buccal mucous membranes, often accompanied by watery discharge from eyes and nose, diarrhoea, loss of condition, and abortion of pregnant animals, and now believed to result from ingestion of the chlorinated naphthalene of various lubricating oils. [EU] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] 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] Hypopigmentation: A condition caused by a deficiency in melanin formation or a loss of pre-existing melanin or melanocytes. It can be complete or partial and may result from trauma, inflammation, and certain infections. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Ichthyosis Vulgaris: Most common form of ichthyosis characterized by prominent scaling especially on the exterior surfaces of the extremities. It is inherited as an autosomal dominant trait. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [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

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Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impetigo: A common superficial bacterial infection caused by staphylococcus aureus or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] 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]

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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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [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] 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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH]

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Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratoacanthoma: A benign, non-neoplastic, usually self-limiting epithelial lesion closely resembling squamous cell carcinoma clinically and histopathologically. It occurs in solitary, multiple, and eruptive forms. The solitary and multiple forms occur on sunlight exposed areas and are identical histologically; they affect primarily white males. The eruptive form usually involves both sexes and appears as a generalized papular eruption. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Keratolytic Agents: Agents that soften, separate, and cause desquamation of the cornified epithelium or horny layer of skin. They are used to expose mycelia of infecting fungi or to treat corns, warts, and certain other skin diseases. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Keratosis Follicularis: A slowly progressive autosomal dominant disorder of keratinization characterized by pinkish-to-tan papules that coalesce to form plaques. These lesions become darker over time and commonly fuse, forming papillomatous and warty malodorous growths. [NIH]

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Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] 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] Koilonychia: Dystrophy of the fingernails, sometimes associated with iron deficiency anaemia, in which they are thin and concave, with the edges raises; called also spoon nail. [EU]

Lacrimal: Pertaining to the tears. [EU] Lacrimal Apparatus: The tear-forming and tear-conducting system which includes the lacrimal glands, eyelid margins, conjunctival sac, and the tear drainage system. [NIH] 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] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentigo: Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome). [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] 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]

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Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lichenification: Hypertrophy of the epidermis, resulting in thickening of the skin with exaggeration of the normal skin markings, giving the skin a leathery barklike appearance, which is caused by prolonged rubbing or scratching. It may arise on seemingly normal skin, or it may develop at the site of another pruritic cutaneous disorder. [EU] 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] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] 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] 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] Lumbago: Pain in the lumbar region. [EU] 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] 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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and

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diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [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]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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]

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Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] 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] Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by burrowing larvae. [NIH] Migration: The systematic movement of genes between populations of the same species,

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geographic race, or variety. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Miscible: Susceptible of being mixed. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] 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] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] 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] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal Diseases: Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU]

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Mycosis: Any disease caused by a fungus. [EU] Mycosis Fungoides: A chronic malignant T-cell lymphoma of the skin. In the late stages the lymph nodes and viscera are affected. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naevus: A circumscribed area of pigmentation or vascularization, usually in the form of a congenital benign neoplasm occurring in the skin or in various ocular tissues. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. [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] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [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] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH]

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Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

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] Nonmelanoma skin cancer: Skin cancer that arises in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin). [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nummular: Coin-sized and coin-shaped. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [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] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the

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lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteotomy: The surgical cutting of a bone. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [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] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH]

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Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar 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] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] 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] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

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Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perineal: Pertaining to the perineum. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [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 stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [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] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] 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

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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] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [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] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Pityriasis Rubra Pilaris: A chronic skin disease characterized by small follicular papules, disseminated reddish-brown scaly patches, and often, palmoplantar hyperkeratosis. The papules are about the size of a pin and topped by a horny plug. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [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.

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Also called thrombocytes. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Podophyllum: A genus of poisonous American herbs, family Berberidaceae. The roots yield podophyllotoxins and other pharmacologically important agents. The plant was formerly used as a cholagogue and cathartic. It is different from the European Mandrake (Mandragora). [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] Polyarthritis: An inflammation of several joints together. [EU] 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] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porokeratosis: A rare, chronic, progressive autosomal dominant disorder seen most often in males and usually appearing in early childhood. It is characterized by the formation of slightly atrophic patches surrounded by an elevated, keratotic border. [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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH]

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Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] 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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [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] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prophylaxis: An attempt to prevent disease. [NIH] 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

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mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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] 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] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH]

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Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoralens: Substances found in many different plants, especially Psoralea corylifolia (Legume). They are used for skin diseases, especially vitiligo and as sunscreens. They interact with nucleic acids and are also used as research tools. Psoralens have a coumarin molecule with a furan ring. [NIH] 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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is

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both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] 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] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] 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 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]

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Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] 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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [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] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinaldehyde: A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in "dark" reactions to return to the native transconfiguration. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous

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membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhagades: Fissures, cracks, or fine linear scars in the skin, especially such lesions around the mouth or other regions subjected to frequent movement. [EU] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] 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] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [NIH] Ruminants: A suborder of the order Artiodactyla whose members have the distinguishing feature of a four-chambered stomach. Horns or antlers are usually present, at least in males. [NIH]

Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme

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dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Saturate: Means fatty acids without double bond. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] 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] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] 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] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [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]

Sialorrhea: Increased salivary flow. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] 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] Skin Neoplasms: Tumors or cancer of the skin. [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] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [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

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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 salicylate: A drug that belongs to the family of drugs called nonsteroidal antiinflammatory drugs. Sodium salicylate may be tolerated by people who are sensitive to aspirin. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] 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] 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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spermine: A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated

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manner. [EU] 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] 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] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [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] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU]

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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] Sublingual: Located beneath the tongue. [EU] Submucous: Occurring beneath the mucosa or a mucous membrane. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subungual: Beneath a nail. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH]

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Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Topical: On the surface of the body. [NIH]

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Topical chemotherapy: Treatment with anticancer drugs in a lotion or cream applied to the skin. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the opening so created. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tretinoin: An important regulator of gene expression, particularly during growth and development and in neoplasms. Retinoic acid derived from maternal vitamin A is essential for normal gene expression during embryonic development and either a deficiency or an excess can be teratogenic. It is also a topical dermatologic agent which is used in the treatment of psoriasis, acne vulgaris, and several other skin diseases. It has also been approved for use in promyelocytic leukemia. [NIH] Trichloroacetic Acid: A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for

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nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor 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 suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] 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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH]

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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] Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the 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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH]

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Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] War: Hostile conflict between organized groups of people. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] 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] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

193

INDEX A Abdomen, 135, 142, 166, 171, 173, 185, 186 Aberrant, 83, 135 Abortion, 135, 161 Acantholysis, 101, 135, 174 Acetone, 6, 135, 165 Acetylcholine, 135, 171 Acitretin, 39, 55, 58, 63, 75, 76, 135 Acne, 75, 81, 86, 87, 88, 90, 91, 92, 93, 96, 135, 164, 189 Acne Vulgaris, 87, 88, 92, 135, 164, 189 Actin, 4, 135, 168 Actinic keratosis, 62, 63, 73, 74, 75, 80, 81, 83, 84, 85, 89, 93, 94, 95, 96, 97, 100, 103, 104, 123 Adaptability, 135, 144 Adherens Junctions, 4, 135 Adjuvant, 135 Adnexa, 90, 135 Adrenal Glands, 136, 137 Adverse Effect, 136, 164, 184 Affinity, 9, 12, 136, 167, 184 Agar, 136, 175 Airway, 136, 143 Algorithms, 136, 142 Alimentary, 136, 173 Alkaline, 136, 137, 143, 172, 174 Alleles, 15, 136 Allergic Rhinitis, 88, 136, 158 Allylamine, 136, 137 Alopecia, 21, 63, 116, 136 Alpha Particles, 136, 180 Alpha-1, 90, 136 Alpha-helix, 136, 164 Alternative medicine, 67, 71, 104, 136 Amber, 136, 162 Ameliorated, 5, 137 Ameliorating, 92, 137 Amine, 84, 97, 137 Amino acid, 137, 138, 139, 151, 154, 155, 158, 160, 168, 172, 174, 177, 178, 184, 187, 188, 189, 190 Amino Acid Sequence, 137, 138, 155 Aminolevulinic Acid, 75, 137 Ammonia, 137, 187, 190 Amyloidosis, 100, 137 Anaemia, 137, 165 Anaesthesia, 137, 162

Analgesic, 137, 150 Analog, 137, 156 Analogous, 88, 137, 189 Anaplasia, 137 Anatomical, 137, 145, 152, 162, 166, 183 Anemia, 117, 137 Angioedema, 100, 138 Angiogenesis, 93, 138, 167 Angiogenesis inhibitor, 93, 138 Angiosarcoma, 93, 138 Animal model, 4, 12, 138 Annealing, 138, 176 Anogenital, 97, 138 Antagonism, 4, 138 Antiarrhythmic, 80, 138 Antibacterial, 80, 138, 185 Antibiotic, 138, 154, 169, 174, 185, 188 Antibodies, 4, 5, 10, 12, 138, 140, 154, 158, 162, 166, 175 Antibody, 5, 24, 136, 138, 147, 149, 154, 158, 160, 162, 164, 169, 180, 185, 192 Anticoagulant, 138, 178 Antidepressant, 138, 148 Antifungal, 80, 138, 165, 168 Antigen, 4, 7, 10, 12, 24, 136, 138, 139, 147, 150, 160, 161, 162, 163, 177 Antigen-presenting cell, 139, 150 Anti-infective, 139, 184 Anti-inflammatory, 8, 89, 92, 139, 140, 144, 150, 182, 185 Anti-Inflammatory Agents, 139, 140, 144 Antimetabolite, 139, 156, 168 Antimycotic, 139, 146 Antineoplastic, 139, 142, 152, 156, 160, 168, 176, 187 Antineoplastic Agents, 139, 152 Antioxidant, 51, 63, 139, 140, 156, 172 Antiproliferative, 41, 139 Antipyretic, 139, 150 Antiseptic, 135, 139 Antitussive, 88, 139 Antiviral, 80, 97, 139 Anus, 138, 139, 142, 147 Aplasia, 69, 139, 152 Apoptosis, 11, 15, 19, 26, 139 Aqueous, 91, 139, 141, 149, 152, 165, 166 Arachidonic Acid, 139, 177 Areola, 63, 139

194

Keratosis

Arginine, 139, 171, 172, 179 Aromatic, 49, 83, 84, 139 Arrhythmia, 138, 139 Arterial, 136, 139, 161, 178 Arteries, 139, 140, 141, 142, 148, 168, 176 Arteriolar, 140, 143 Arterioles, 140, 142 Arteriolosclerosis, 92, 140 Arteritis, 100, 140 Artery, 139, 140, 141, 142, 148, 173 Arthralgia, 92, 140 Ascorbic Acid, 86, 140, 160 Aseptic, 140, 172 Aspirin, 140, 185 Ataxia, 117, 140, 145, 188 Atopic, 34, 88, 92, 97, 140 Atrophy, 86, 94, 116, 117, 135, 140 Atypical, 69, 85, 140, 151 Auditory, 17, 140, 167 Auditory nerve, 140, 167 Autoantibodies, 3, 7, 8, 12, 140 Autoantigens, 140 Autoimmune disease, 5, 7, 10, 12, 100, 140 Autoimmunity, 5, 140 Autonomic, 135, 140, 148, 170, 174 Autonomic Nervous System, 140, 170, 174 B Bacteria, 138, 141, 155, 168, 179, 184, 185, 186, 189, 191 Bacteriophage, 141, 175, 189 Basal cell carcinoma, 63, 73, 74, 75, 76, 84, 89, 93, 97 Basal cells, 14, 23, 141, 171 Basal Ganglia, 140, 141 Basal Ganglia Diseases, 140, 141 Base, 8, 82, 141, 150, 164, 174, 188 Basement Membrane, 4, 8, 10, 63, 141, 144, 155, 165 Basilar Artery, 141, 167 Baths, 122, 141 Benign, 8, 20, 21, 33, 37, 94, 96, 100, 122, 133, 140, 141, 154, 158, 164, 170, 171, 173, 180 Beta carotene, 67, 141 Bilateral, 62, 141, 181 Bile, 141, 156, 160, 166, 186 Biochemical, 5, 11, 15, 41, 94, 136, 139, 142 Biomarkers, 13, 29, 142 Biopsy, 58, 142, 174 Biotechnology, 16, 101, 104, 113, 115, 116, 117, 118, 142 Bladder, 93, 142, 178, 190

Bleomycin, 84, 142 Blister, 142, 174 Blood Coagulation, 142, 143, 188 Blood pressure, 142, 161, 185 Blood transfusion, 68, 142 Blood vessel, 138, 142, 145, 153, 159, 164, 168, 184, 185, 186, 187, 188, 191 Body Fluids, 142, 185, 190 Body Mass Index, 34, 142 Bone Marrow, 70, 80, 142, 149, 157, 158, 166, 177, 185 Boron, 142, 149 Bowel, 142, 150, 174, 186 Bowel Movement, 142, 150, 186 Bowen, 19, 21, 23, 27, 35, 36, 38, 43, 49, 51, 52, 58, 62, 63, 68, 85, 142 Brachial, 92, 142 Brachytherapy, 143, 163, 164, 180, 192 Bradykinin, 143, 171 Branch, 131, 143, 167, 173, 185, 188 Breakdown, 96, 143, 150, 157, 171 Bronchi, 143, 189 Bronchial, 88, 143 Bronchiectasis, 88, 143 Bronchioles, 143 Bronchiolitis, 88, 143 Bronchitis, 88, 143 Bronchodilator, 88, 143 Buccal, 75, 143, 161, 166, 186 Bullous, 4, 7, 8, 12, 24, 100, 143, 159 Bunion, 45, 124, 143 C Cadherins, 135, 143 Calcium, 6, 86, 143, 147, 167 Callus, 96, 143, 164 Carbon Dioxide, 91, 92, 143, 149, 181 Carbuncle, 92, 143 Carcinogen, 15, 143 Carcinogenesis, 11, 13, 94, 143, 145 Carcinogenic, 143, 171, 177, 186 Carcinoma, 75, 96 Carcinoma in Situ, 22, 35, 96, 144 Cardiac, 80, 136, 138, 144, 170, 186 Carotene, 67, 141, 144, 181 Carotenoids, 141, 144 Case report, 44, 48, 69, 144 Case series, 20, 144 Case-Control Studies, 13, 144 Catabolism, 5, 144 Caustic, 95, 144, 184, 189 Celecoxib, 73, 144

195

Cell, 4, 8, 9, 11, 12, 14, 15, 69, 75, 80, 83, 87, 89, 100, 116, 117 Cell Adhesion, 8, 143, 144, 163 Cell Adhesion Molecules, 8, 144 Cell Death, 9, 139, 144 Cell Division, 11, 116, 141, 144, 169, 175 Cell Lineage, 4, 144 Cell membrane, 135, 144, 146, 157, 175 Cell proliferation, 80, 144 Cell Respiration, 145, 169, 181 Cerebellar, 140, 145, 180, 189 Cerebellar Diseases, 140, 145, 189 Cerebral, 116, 140, 141, 145 Cerebral Cortex, 140, 145 Cerebrum, 145, 190 Cervical, 89, 90, 93, 145 Cervix, 135, 145 Cheilitis, 123, 145 Chemexfoliation, 83, 145 Chemoprevention, 13, 15, 73, 74, 145 Chemopreventive, 15, 145 Chemotaxis, 8, 145 Chemotherapy, 37, 69, 96, 145 Chin, 30, 31, 145, 168 Cholesterol, 141, 145, 186 Chondrocytes, 145, 156 Chorioretinitis, 145, 181 Choroid, 145, 181 Chromatin, 139, 145, 153 Chromosome, 7, 35, 43, 145, 166, 169 Chronic renal, 146, 176 Cicatricial, 6, 8, 21, 146 Cicatrix, 146, 164 Cicatrix, Hypertrophic, 146, 164 CIS, 13, 146, 181 Citrus, 69, 140, 146 Clinical trial, 3, 13, 58, 73, 76, 113, 146, 149, 151, 180 Clone, 12, 15, 146 Cloning, 7, 142, 146 Clotrimazole, 85, 146 Cod Liver Oil, 146, 152 Coenzyme, 140, 146 Cofactor, 146, 178, 188 Collagen, 12, 96, 137, 141, 146, 155, 156, 164, 167, 175, 177 Collapse, 143, 146 Colon, 33, 116, 147, 165 Complement, 147, 157, 163 Complementary and alternative medicine, 67, 71, 147 Complementary medicine, 67, 147

Complete remission, 91, 147, 181 Complete response, 147 Compound nevus, 21, 147 Computational Biology, 113, 115, 147 Concentric, 140, 147 Congenita, 14, 116, 147, 152 Congestion, 148, 154 Conjunctiva, 6, 54, 148 Conjunctivitis, 88, 148, 158 Connective Tissue, 7, 140, 142, 146, 148, 150, 156, 164, 166, 168, 169, 182, 183 Connective Tissue Cells, 148 Connexins, 148, 157 Constipation, 91, 92, 148 Constitutional, 148, 181 Consumption, 14, 148, 173 Contact dermatitis, 82, 148 Contraindications, ii, 148 Cornea, 148, 183 Corneal Ulcer, 53, 148 Corneum, 90, 91, 95, 101, 148, 153, 161 Coronary, 148, 168 Coronary Thrombosis, 148, 168 Cotinine, 15, 148 Coumarin, 148, 179 Cranial, 140, 148, 155, 170, 171, 174 Cranial Nerves, 148, 170 Cryosurgery, 96, 123, 148 Cryotherapy, 51, 148 Cues, 5, 148 Cultured cells, 8, 15, 149 Curative, 84, 149, 188 Curcumin, 93, 149 Curettage, 123, 149 Curette, 149 Cutaneous, 9, 12, 68, 75, 76, 81, 85, 87, 99 Cyclic, 149, 158, 171, 178 Cyclin, 11, 24, 149 Cyclosporine, 20, 149 Cytokines, 8, 9, 149 Cytoplasm, 139, 144, 149, 153, 158 Cytoskeleton, 4, 135, 149, 163, 168 Cytotoxic, 84, 149, 180 Cytotoxicity, 84, 136, 149 D Deamination, 149, 190 Decarboxylation, 149, 172, 179 Decubitus, 92, 149 Decubitus Ulcer, 92, 149 Defecation, 92, 149 Defense Mechanisms, 149, 163 Deletion, 6, 40, 41, 52, 139, 149

196

Keratosis

Denaturation, 149, 176 Dendrites, 150 Dendritic, 9, 150, 167 Dendritic cell, 9, 150 Density, 75, 142, 150, 171 Depigmentation, 150, 191 Depressive Disorder, 150, 166 Dermal, 8, 97, 150, 152 Dermatitis, 25, 80, 82, 88, 92, 97, 100, 101, 122, 150, 152 Dermatologist, 96, 150 Dermatosis, 8, 100, 150 Dermis, 87, 89, 138, 145, 147, 150, 164, 168, 181, 187 Dermo-epidermal, 150, 154 Desmosomes, 14, 150, 159 Desquamation, 86, 87, 150, 164 Detoxification, 9, 150 Diagnostic procedure, 79, 104, 150 Diaper Rash, 82, 150 Diarrhoea, 150, 161 Diclofenac, 89, 108, 150 Diclofenac Sodium, 89, 150 Diethylcarbamazine, 150, 187 Difluoromethylornithine, 13, 150 Digestion, 136, 141, 142, 150, 166, 186, 191 Digestive system, 77, 150 Digestive tract, 150, 184, 186 Dilatation, 135, 138, 143, 151, 191 Dimethyl, 23, 151 Diploid, 151, 169, 175 Direct, iii, 5, 84, 107, 151, 154, 173, 180 Discrete, 101, 151 Disease Progression, 7, 151 Dissociation, 136, 151, 163 Distal, 26, 43, 151, 179 Dorsal, 151, 154, 176 Double-blind, 28, 151 Drug Interactions, 108, 151 Drug Resistance, 80, 151 Drug Tolerance, 151 Dysplasia, 7, 35, 48, 117, 151 Dysplastic nevi, 13, 151 Dysplastic nevus, 42, 151 Dystrophic, 11, 27, 93, 152, 153 Dystrophy, 117, 152, 165 E Ear Diseases, 70, 152 Ectoderm, 152 Ectodermal Dysplasia, 7, 152 Eczema, 80, 82, 92, 93, 122, 152 Edema, 138, 148, 152

Efficacy, 29, 53, 56, 76, 89, 152 Eflornithine, 73, 74, 152 Elasticity, 82, 87, 152 Elastin, 96, 146, 152, 155 Elective, 10, 55, 152 Electrolyte, 152, 176, 185 Embryo, 135, 144, 152, 162 Emulsion, 81, 152 Enamel, 152, 164 Endemic, 12, 152, 185 Endogenous, 5, 140, 152, 172 Endopeptidases, 153, 178 Endothelial cell, 153, 156, 188 Endothelium, 153, 171 Endothelium-derived, 153, 171 Endotoxins, 147, 153, 165 End-stage renal, 146, 153, 176 Environmental Exposure, 153, 171 Environmental Health, 19, 112, 114, 153 Enzymatic, 6, 137, 143, 144, 147, 153, 176, 181 Enzyme, 9, 146, 152, 153, 157, 158, 176, 178, 180, 182, 187, 188, 191, 192 Eosinophilic, 100, 101, 153 Eosinophils, 8, 153, 158, 166 Epidermal, 4, 6, 7, 8, 9, 10, 14, 27, 80, 86, 91, 101, 153, 164, 167, 191 Epidermis, 4, 11, 13, 80, 87, 89, 90, 101 Epidermodysplasia Verruciformis, 54, 102, 153 Epidermoid carcinoma, 153, 186 Epidermolysis Bullosa, 6, 8, 11, 27, 75, 93, 153 Epidermolysis Bullosa Acquisita, 6, 153 Epithelial, 4, 13, 28, 36, 80, 83, 84, 85, 87, 96, 144, 148, 150, 154, 164, 165, 173 Epithelial Cells, 154, 165 Epithelioma, 142, 154 Epithelium, 4, 86, 141, 145, 150, 153, 154, 164, 173 Epitope, 12, 154 Epitope Mapping, 12, 154 Erythema, 100, 148, 154, 187, 190 Erythema Infectiosum, 154 Erythema Multiforme, 100, 154 Erythrocytes, 137, 142, 154 Erythromycin, 154, 182 Esophagus, 10, 150, 151, 154, 174, 186 Essential Tremor, 117, 154 Ether, 81, 154 Etretinate, 28, 62, 135, 154 Eukaryotic Cells, 154, 172

197

Evacuation, 148, 154 Exanthema, 94, 154 Excipient, 89, 155 Exfoliation, 83, 150, 155 Exhaustion, 138, 155 Exogenous, 152, 155, 157 Exon, 10, 155 Expiration, 155, 181 Extensor, 155, 179, 191 External-beam radiation, 155, 164, 180, 192 Extracellular, 6, 7, 135, 148, 155, 156, 159, 163, 167, 185 Extracellular Matrix, 148, 155, 156, 159, 163, 167 Extracellular Matrix Proteins, 155, 159, 167 Extraocular, 135, 155 Extremity, 92, 155 F Facial, 87, 88, 96, 100, 155, 167, 173 Facial Nerve, 155, 173 Family Planning, 113, 155 Fat, 27, 139, 141, 142, 144, 149, 155, 165, 166, 182, 183, 185 Fatty acids, 155, 177, 183, 184 Febrile, 100, 155 Feces, 148, 150, 155, 186 Fibroblast Growth Factor, 93, 155 Fibroblasts, 7, 148, 156 Fibrosis, 100, 117, 136, 156, 183 Fluorouracil, 23, 27, 28, 29, 32, 50, 53, 55, 56, 80, 84, 95, 96, 123, 156 Fold, 12, 156, 171 Follicles, 14, 122, 156 Folliculitis, 92, 156 Foramen, 145, 156, 167 Forearm, 13, 142, 156 Founder Effect, 7, 156 Free Radicals, 94, 139, 151, 156 Fungi, 138, 139, 156, 164, 168, 188, 192 Fungus, 156, 170 Furunculosis, 92, 156 G Gallate, 13, 156 Gallbladder, 150, 156 Ganglia, 135, 141, 156, 170, 174 Ganglioside, 82, 156 Gangrene, 92, 156 Gap Junctions, 37, 148, 156 Gas, 137, 143, 157, 160, 169, 171 Gastrin, 157, 160

Gels, 87, 157 Gene, 5, 7, 11, 12, 14, 16, 75, 101, 118, 119 Gene Expression, 5, 118, 157, 189 Gene Targeting, 5, 157 Gene Therapy, 14, 157 Genetic Engineering, 142, 146, 157 Genetic testing, 157, 176 Genetics, 5, 7, 11, 28, 31, 32, 35, 38, 40, 41, 43, 44, 46, 53, 157 Genital, 84, 89, 157, 182, 190 Genitourinary, 19, 62, 68, 157, 190 Genotype, 12, 56, 157, 174 Gingival Hyperplasia, 100, 157 Gingival Recession, 14, 157 Gingivitis, 92, 100, 157 Gland, 100, 157, 166, 173, 175, 178, 183, 187, 188 Glossitis, 100, 158 Glucose, 117, 140, 158, 159, 182 Glycine, 137, 158, 184 Glycoprotein, 158, 165, 167, 188 Goats, 63, 158 Gonadal, 158, 186 Governing Board, 158, 177 Graft, 68, 92, 100, 158, 160 Grafting, 4, 158 Graft-versus-host disease, 68, 100, 158 Granular Cell Tumor, 100, 158 Granulocytes, 158, 165, 192 Granulomas, 93, 158 Guanylate Cyclase, 158, 171 H Hair follicles, 14, 122, 150, 156, 158, 186, 192 Half-Life, 135, 158 Halitosis, 100, 158 Haptens, 136, 158 Hay Fever, 136, 158 Health Status, 14, 158 Heme, 137, 158 Hemidesmosomes, 4, 12, 159 Hemoglobin, 138, 154, 158, 159 Hemoglobinopathies, 157, 159 Hemoglobinuria, 117, 159 Hemolytic, 159, 162 Hemorrhage, 100, 159, 186 Hemostasis, 159, 163 Hepatic, 9, 80, 159 Hereditary, 30, 34, 40, 91, 122, 152, 159, 181 Heredity, 135, 157, 159 Herpes, 8, 159

198

Keratosis

Herpes Gestationis, 8, 159 Herpes Zoster, 159 Herpetiformis, 25, 159 Heterodimers, 159, 163 Heterogeneity, 46, 136, 159 Homeostasis, 4, 6, 159 Homogeneous, 140, 160 Homologous, 136, 148, 157, 160 Hormonal, 140, 160 Hormone, 29, 157, 160, 177, 182, 188 Horny layer, 153, 160, 164 Host, 141, 160, 190, 191 Human papillomavirus, 25, 26, 34, 35, 36, 47, 50, 70, 97, 153, 160 Humoral, 5, 160 Humour, 160 Hybrid, 5, 146, 160 Hydroalcoholic, 86, 160 Hydrogen, 137, 141, 149, 155, 160, 169, 170, 172, 178 Hydrolysis, 96, 160, 178 Hydrophilic, 83, 160 Hydrophobic, 97, 160 Hydroxy Acids, 81, 91, 160 Hydroxylamine, 9, 160 Hydroxylysine, 146, 160 Hydroxyproline, 137, 146, 160 Hydroxyurea, 46, 160 Hyperhidrosis, 22, 42, 90, 160 Hyperkeratosis, 14, 16, 28, 30, 33, 50, 62, 63, 70, 74, 91, 161, 175 Hyperpigmentation, 54, 86, 87, 161 Hyperplasia, 35, 100, 161 Hypersensitivity, 9, 161, 182 Hypertension, 140, 161, 188 Hypertrophy, 161, 166 Hypopigmentation, 22, 35, 161 Hypoplasia, 152, 161 Hypothyroidism, 58, 63, 161 I Ichthyosis, 6, 44, 69, 74, 75, 81, 88, 90, 91, 92, 116, 161 Ichthyosis Vulgaris, 6, 161 Id, 64, 70, 116, 124, 125, 130, 132, 161 Imidazole, 146, 161, 168 Immersion, 6, 141, 161 Immune response, 4, 5, 97, 135, 138, 139, 140, 158, 161, 162, 187, 190, 191 Immune system, 139, 140, 161, 162, 166, 167, 174, 191, 192 Immunity, 6, 10, 153, 161 Immunochemistry, 154, 162

Immunodeficiency, 28, 117, 162 Immunofluorescence, 154, 162 Immunoglobulin, 138, 162, 169 Immunohistochemistry, 23, 36, 162 Immunology, 135, 136, 162 Immunosuppressant, 156, 162, 168 Impairment, 140, 162, 168 Impetigo, 92, 162 Implant radiation, 162, 163, 164, 180, 192 In situ, 47, 96, 162 In vitro, 8, 9, 14, 157, 162, 176, 188 In vivo, 4, 5, 6, 7, 8, 14, 157, 162, 172 Incision, 45, 162, 163 Incubated, 9, 162 Indicative, 162, 173, 191 Induction, 11, 37, 70, 162 Induction therapy, 70, 162 Infarction, 148, 162, 168, 176 Infection, 6, 10, 100, 124 Infiltration, 37, 85, 163 Infusion, 163, 168, 189 Ingestion, 158, 161, 163 Inguinal, 160, 163 Inorganic, 160, 163 Insight, 11, 163 Integrins, 8, 159, 163 Intercellular Junctions, 4, 163 Intermediate Filaments, 159, 163 Internal radiation, 163, 164, 180, 192 Interstitial, 143, 163, 164, 192 Intestinal, 144, 163, 167 Intoxication, 163, 192 Intracellular, 8, 159, 162, 163, 171, 176, 178 Intramuscular, 163, 173 Intravenous, 163, 168, 173 Intrinsic, 81, 90, 136, 141, 163 Invasive, 37, 85, 161, 163 Involuntary, 141, 154, 163, 170, 184 Ionization, 163 Ionizing, 96, 136, 153, 163, 180 Ions, 141, 151, 152, 160, 163, 164 Irradiation, 81, 164, 192 Ischemia, 140, 149, 156, 164 Isotretinoin, 62, 108, 164 J Joint, 35, 140, 164, 187 K Kb, 112, 164 Keloid, 96, 146, 164 Keratin, 13, 16, 35, 36, 164, 183 Keratinocytes, 4, 7, 9, 14, 15, 26, 38, 80, 85, 164

199

Keratoacanthoma, 36, 52, 80, 164 Keratolytic, 70, 88, 164, 176 Keratolytic Agents, 88, 164 Keratosis Follicularis, 68, 75, 101, 116 Keto, 91, 165 Ketoacidosis, 135, 165 Ketoconazole, 85, 165 Ketone Bodies, 135, 165 Kidney Disease, 77, 112, 117, 165 Kinetic, 163, 165 Koilonychia, 40, 165 L Lacrimal, 135, 155, 165 Lacrimal Apparatus, 135, 165 Laminin, 141, 155, 165 Large Intestine, 150, 151, 165, 180, 184 Laryngeal, 10, 165 Larynx, 26, 47, 165, 189, 191 Latent, 165, 177 Lens, 147, 165 Lentigo, 26, 54, 165 Lethargy, 161, 165 Leucocyte, 90, 136, 165 Leukemia, 68, 116, 157, 166, 177 Leukocytes, 142, 149, 153, 158, 166 Leukocytosis, 143, 166 Leukoplakia, 14, 85, 100, 166 Library Services, 130, 166 Lichenification, 80, 166 Ligament, 166, 178 Ligands, 144, 163, 166 Linkage, 32, 38, 43, 166 Linkages, 5, 159 Lip, 28, 123, 166 Lipid, 6, 43, 82, 165, 166 Liquor, 166, 179 Lithium, 23, 166 Liver, 9, 30, 137, 139, 141, 150, 152, 155, 156, 159, 165, 166, 190 Localization, 36, 46, 162, 166 Localized, 43, 80, 84, 137, 138, 150, 160, 162, 165, 166, 175, 183, 190 Lumbago, 92, 166 Lumbar, 166 Lupus, 100, 166 Lymph, 145, 153, 160, 166, 170 Lymph node, 145, 166, 170 Lymphatic, 153, 162, 166, 168, 185 Lymphocyte, 138, 166 Lymphoid, 138, 165, 167 Lymphoma, 20, 68, 116, 167, 170

M Macrophage, 7, 167 Macrophage Colony-Stimulating Factor, 7, 167 Malabsorption, 117, 167 Malignancy, 44, 49, 167, 173 Malignant, 11, 83, 84, 85, 93, 95, 100, 116 Malignant tumor, 100, 144, 167 Malnutrition, 140, 167, 169 Mandible, 145, 167 Manic, 166, 167 Matrix metalloproteinase, 29, 167 Meat, 96, 167 Meat Products, 96, 167 Meatus, 17, 167 Mediate, 7, 144, 167 Medical Records, 167, 182 MEDLINE, 113, 115, 117, 167 Melanin, 45, 150, 161, 167 Melanocytes, 161, 167, 168, 171 Melanoma, 13, 22, 26, 33, 42, 44, 45, 52, 54, 83, 89, 90, 93, 103, 116, 122, 168, 190 Membrane, 8, 10 Meningeal, 37, 168 Meninges, 168 Mental, iv, 3, 29, 77, 112, 114, 118, 145, 151, 161, 168, 179, 183 Mental Disorders, 77, 168 Mesenchymal, 87, 167, 168 Metabolite, 135, 151, 168 Metastasis, 85, 144, 167, 168 Metastatic, 45, 55, 168, 183 Methionine, 151, 168 Methotrexate, 80, 168 Methyl Methanesulfonate, 26, 168 MI, 31, 134, 168 Miconazole, 85, 168 Microbe, 168, 189 Microbiology, 140, 168 Microfilaments, 135, 163, 168 Microorganism, 146, 168, 191 Microscopy, 23, 141, 168 Microtubules, 4, 163, 168 Migrans, 94, 100, 168 Migration, 8, 28, 168 Minocycline, 49, 169 Miscible, 97, 169 Mitochondria, 169, 172 Mitosis, 139, 169 Mitotic, 14, 169 Molecular, 4, 6, 7, 11, 12, 13, 46, 82, 87, 89, 113, 115, 136, 142, 147, 169, 190

200

Keratosis

Molecule, 5, 138, 141, 146, 147, 149, 151, 153, 154, 159, 160, 169, 172, 179, 180, 191 Monoclonal, 12, 164, 169, 180, 192 Monocyte, 167, 169 Mononuclear, 167, 169 Monosomy, 57, 169 Morphogenesis, 4, 169 Morphological, 25, 152, 156, 167, 169 Morphology, 159, 169 Mucins, 169, 182 Mucocutaneous, 91, 92, 169 Mucosa, 50, 53, 99, 143, 166, 169, 186, 187 Muscle Fibers, 169 Muscular Atrophy, 117, 169 Muscular Dystrophies, 152, 169 Musculoskeletal Diseases, 91, 92, 169 Mutagen, 168, 169 Mutagenic, 82, 169 Myalgia, 92, 169 Mycosis, 23, 46, 58, 63, 170 Mycosis Fungoides, 23, 58, 63, 170 Myocardium, 168, 170 Myotonic Dystrophy, 117, 170 N Naevus, 68, 170 NCI, 1, 73, 74, 75, 76, 111, 146, 170 Need, 99, 100, 101, 126, 146, 167, 170 Neonatal, 9, 170 Neoplasia, 17, 116, 154, 170 Neoplasm, 154, 158, 170, 173, 183 Neoplastic, 80, 84, 87, 94, 137, 164, 167, 170 Nephropathy, 165, 170 Nerve, 140, 145, 150, 155, 170, 171, 182, 183, 186, 188, 191 Nervous System, 91, 92, 117, 135, 141, 156, 170, 172, 174 Nervous System Diseases, 91, 92, 170 Neural, 30, 160, 170 Neuralgia, 92, 170 Neuromuscular, 135, 170 Neuromuscular Junction, 135, 170 Neuropathy, 92, 170 Neuroretinitis, 170, 181 Neutrons, 136, 164, 170, 180 Neutrophil, 8, 170 Nevus, 102, 147, 151, 165, 171 Night Blindness, 171, 181 Nitric Oxide, 47, 160, 171 Nitrogen, 89, 137, 155, 171, 190 Nonmelanoma skin cancer, 74, 171 Nuclei, 136, 157, 169, 170, 171, 172, 178

Nucleic acid, 171, 179, 185 Nucleus, 139, 141, 145, 149, 153, 154, 163, 169, 170, 171, 178, 186, 188 Nummular, 92, 171 O Ocular, 6, 10, 48, 170, 171 Odour, 139, 171 Office Visits, 18, 171 Ointments, 171, 184 Omentum, 82, 171 Oncogene, 11, 117, 171 Oncogenic, 11, 163, 171 Opacity, 150, 171 Opsin, 171, 181, 182 Optic Nerve, 170, 171, 181, 183 Oral Health, 14, 172 Oral Hygiene, 158, 172 Orbit, 172 Orbital, 37, 172 Organ Culture, 11, 172, 188 Organelles, 4, 149, 167, 172, 175 Ornithine, 152, 172, 179 Ornithine Decarboxylase, 152, 172 Orofacial, 100, 172 Osteotomy, 26, 42, 48, 172 Otitis, 124, 172 Otitis Media, 124, 172 Oxidants, 8, 172 Oxidation, 139, 172 Oxidation-Reduction, 172 Oxides, 84, 172 Oxygen Consumption, 173, 181 P P53 gene, 18, 173 Palate, 173, 186 Palliative, 173, 188 Pancreas, 142, 150, 173, 190 Pancreatic, 117, 173 Pancreatic cancer, 117, 173 Papillary, 161, 173 Papilloma, 20, 26, 86, 89, 90, 93, 154, 173 Papillomavirus, 37, 70, 97, 173 Parasite, 173 Parasitic, 100, 173 Parasitic Diseases, 100, 173 Parenteral, 63, 173 Parotid, 100, 173 Paroxysmal, 117, 173 Partial remission, 173, 181 Patch, 150, 166, 173 Pathogenesis, 13, 50, 70, 101, 173

201

Pathologic, 50, 54, 139, 142, 148, 161, 173, 179 Pathologic Processes, 139, 173 Patient Education, 122, 128, 130, 134, 173 Pelvic, 174, 178 Pemphigus, 12, 37, 50, 101, 135, 174 Penicillin, 138, 174 Peptide, 4, 96, 137, 153, 155, 164, 174, 178, 180, 188 Percutaneous, 85, 87, 174 Perforation, 53, 156, 174 Perineal, 160, 174 Periodontal disease, 44, 174 Periodontitis, 157, 174 Perioral, 99, 174 Peripheral blood, 12, 174 Peripheral Nervous System, 170, 174, 187 Peripheral stem cells, 158, 174 Peritoneum, 171, 174 Petrolatum, 152, 174 Phagocyte, 167, 172, 174 Pharmacologic, 8, 15, 158, 174, 189 Pharynx, 10, 14, 174 Phenolphthalein, 152, 174 Phenotype, 12, 21, 36, 174 Phospholipids, 155, 174 Phosphorus, 143, 175 Photodynamic therapy, 50, 51, 75, 175 Photosensitizer, 42, 175 Physical Examination, 75, 175 Physiologic, 158, 175, 178, 180, 189 Physiology, 5, 175 Pigmentation, 19, 62, 68, 80, 96, 100, 161, 170, 175 Pigments, 144, 175, 181 Pilot study, 67, 175 Pituitary Gland, 155, 175 Pityriasis, 30, 92, 175 Pityriasis Rubra Pilaris, 30, 175 Plana, 102, 175 Plants, 143, 146, 158, 169, 175, 179, 182, 189 Plaque, 50, 175 Plasma, 51, 63, 85, 100, 135, 138, 144, 159, 175, 180, 183 Plasma cells, 85, 138, 175 Plastids, 172, 175 Platelet Aggregation, 171, 175 Platelets, 171, 175 Pleated, 164, 176 Pneumonia, 148, 176 Podophyllotoxin, 84, 176

Podophyllum, 86, 176 Polyarteritis Nodosa, 100, 176 Polyarthritis, 92, 176 Polycystic, 117, 176 Polymerase, 26, 176 Polymerase Chain Reaction, 26, 176 Polymorphic, 94, 145, 176 Polymorphism, 22, 176 Polysaccharide, 138, 176, 178 Porokeratosis, 49, 62, 70, 101, 116, 176 Posterior, 140, 141, 145, 151, 173, 176, 183 Postnatal, 176, 186 Potassium, 41, 83, 176, 184 Practice Guidelines, 114, 123, 125, 177 Precancerous, 15, 85, 95, 96, 135, 145, 177 Preclinical, 13, 177 Precursor, 139, 141, 153, 177, 185, 190 Predisposition, 9, 88, 177 Premalignant, 19, 55, 84, 86, 87, 177 Prevalence, 12, 52, 56, 177 Prickle, 135, 164, 177 Progesterone, 177, 186 Progression, 7, 13, 52, 63, 138, 177 Progressive, 11, 30, 140, 146, 148, 151, 158, 164, 169, 170, 176, 177, 181 Proliferating Cell Nuclear Antigen, 29, 177 Proline, 146, 160, 177 Promoter, 15, 177 Promyelocytic leukemia, 177, 189 Prophylaxis, 87, 154, 177, 190 Prospective study, 22, 177 Prostaglandin, 89, 177 Prostaglandins A, 178 Prostate, 55, 117, 142, 178, 190 Protease, 90, 93, 178 Protease Inhibitors, 90, 93, 178 Protein C, 83, 84, 137, 141, 164, 178, 190 Protein S, 8, 101, 117, 118, 142, 154, 178, 188 Proteoglycans, 141, 155, 178 Proteolytic, 8, 136, 147, 178 Protons, 136, 160, 163, 178, 180 Protozoa, 168, 178, 179, 189 Protozoal, 100, 179 Proximal, 151, 179 Pruritic, 101, 152, 166, 179 Pruritus, 179 Psoralens, 81, 179 Psoriasis, 19, 38, 41, 62, 68, 70, 75, 76, 80, 87, 88, 92, 93, 95, 100, 135, 154, 179, 189 Psychic, 168, 179, 183

202

Keratosis

Psychoactive, 179, 192 Public Policy, 113, 179 Puerperium, 159, 179 Pulmonary, 142, 148, 153, 179 Purines, 179, 184 Purulent, 179 Pustular, 135, 159, 162, 179 Putrefaction, 156, 179 Putrescine, 31, 172, 179, 185 Pyoderma, 92, 179 Pyogenic, 93, 179 Pyrimidines, 179, 184 Q Quiescent, 179, 191 R Race, 169, 179 Radiation, 53, 85, 94, 95, 96, 153, 155, 156, 163, 164, 180, 190, 192 Radiation therapy, 53, 155, 163, 164, 180, 192 Radioactive, 158, 160, 162, 163, 164, 171, 180, 192 Radiolabeled, 164, 180, 192 Radiological, 174, 180 Radiotherapy, 143, 164, 180, 192 Randomized, 13, 51, 53, 67, 74, 75, 152, 180 Ras gene, 18, 180 Receptor, 4, 5, 6, 22, 29, 57, 138, 167, 180 Recombinant, 8, 9, 12, 180, 191 Recombinant Proteins, 12, 180 Recombination, 157, 180 Reconstitution, 8, 180 Rectum, 139, 142, 147, 149, 150, 151, 157, 165, 178, 180 Recurrence, 73, 74, 84, 88, 145, 180 Red Nucleus, 140, 180 Reductase, 168, 180 Refer, 1, 143, 147, 156, 159, 166, 170, 180 Refraction, 181, 185 Regeneration, 96, 156, 180, 181 Regimen, 84, 152, 181 Remission, 89, 91, 180, 181 Resection, 84, 89, 181 Respiration, 88, 143, 181 Restoration, 180, 181, 192 Reticular, 58, 181 Retina, 145, 165, 170, 171, 181, 182 Retinal, 171, 181, 182 Retinaldehyde, 17, 62, 181 Retinitis, 48, 181 Retinitis Pigmentosa, 48, 181 Retinoblastoma, 24, 117, 181

Retinoid, 49, 75, 76, 135, 154, 181 Retinol, 65, 96, 181, 182 Retrospective, 17, 42, 62, 182 Retrospective study, 17, 62, 182 Retroviral vector, 157, 182 Rhagades, 92, 182 Rheumatism, 182 Rheumatoid, 80, 92, 172, 182 Rheumatoid arthritis, 80, 92, 182 Rhinitis, 88, 182 Rhodopsin, 171, 181, 182 Ribonucleoside Diphosphate Reductase, 160, 182 Risk factor, 13, 14, 100, 177, 182 Rod, 8, 13, 182 Roxithromycin, 17, 182 Ruminants, 158, 182 Rural Population, 14, 182 S Salicylate, 13, 83, 182, 185 Salicylic, 86, 182 Saliva, 15, 182 Salivary, 150, 155, 173, 182, 184, 192 Salivary glands, 150, 155, 182 Saponins, 182, 186 Sarcoma, 90, 93, 183 Saturate, 10, 183 Scatter, 183, 190 Schizoid, 183, 192 Schizophrenia, 183, 192 Schizotypal Personality Disorder, 183, 192 Sclera, 145, 148, 183 Scleroderma, 100, 140, 183 Scleroproteins, 164, 183 Sclerosis, 93, 117, 140, 183 Screening, 9, 146, 183 Sebaceous, 51, 54, 150, 183, 192 Sebaceous gland, 150, 183, 192 Sebum, 135, 183 Secondary tumor, 168, 183 Secretion, 6, 135, 160, 161, 169, 183, 191 Secretory, 90, 183 Seizures, 173, 183 Semen, 178, 183 Semisynthetic, 169, 182, 184 Senile, 21, 23, 47, 56, 85, 87, 88, 96, 135, 165, 184 Sequencing, 176, 184 Sequester, 11, 184 Serine, 90, 93, 153, 184 Serum, 5, 30, 88, 147, 180, 184 Sex Determination, 117, 184

203

Shedding, 96, 150, 184 Shock, 184, 189 Sialorrhea, 100, 184 Side effect, 81, 82, 88, 91, 92, 100, 107, 136, 184, 189 Signs and Symptoms, 91, 176, 181, 184 Skeleton, 135, 164, 178, 184 Skin graft, 92, 184 Skin Neoplasms, 153, 184 Skull, 75, 172, 184, 188 Small intestine, 160, 184 Smallpox, 124, 184 Smooth muscle, 136, 143, 148, 184, 187 Sneezing, 184 Soaps, 122, 184 Sodium, 13, 83, 89, 150, 184, 185, 187 Sodium salicylate, 13, 83, 185 Soft tissue, 100, 142, 184, 185 Solid tumor, 138, 142, 185 Solvent, 83, 84, 86, 135, 185 Somatic, 148, 160, 169, 174, 185 Specialist, 126, 185 Species, 14, 136, 156, 160, 168, 169, 173, 179, 185, 186, 187, 188, 191, 192 Specificity, 12, 136, 143, 153, 185 Spectrum, 20, 87, 146, 149, 165, 182, 185 Sperm, 145, 185, 190 Spermidine, 31, 172, 185 Spermine, 31, 185 Sphincter, 165, 185 Spinal cord, 142, 145, 168, 170, 174, 185 Spinous, 101, 153, 164, 185 Spirochete, 185, 187 Spleen, 137, 166, 185 Sporadic, 181, 185 Squamous, 13, 63, 73, 74, 75, 80, 84, 85, 89, 93, 95, 96, 123 Squamous cell carcinoma, 13, 63, 73, 74, 75, 80, 85, 93, 95, 96, 123 Squamous cells, 85, 158, 171, 186 Staphylococcus, 143, 156, 162, 169, 186 Staphylococcus aureus, 143, 162, 186 Stem Cells, 4, 174, 186 Steroid, 81, 82, 182, 186 Stomach, 150, 151, 154, 157, 160, 171, 174, 182, 184, 185, 186 Stomatitis, 92, 100, 186 Stool, 147, 165, 186 Strand, 176, 186 Streptococci, 162, 186 Stress, 13, 141, 177, 182, 186, 190 Stria, 94, 116, 186

Stroke, 77, 112, 186 Subacute, 162, 186 Subclinical, 87, 162, 183, 187 Subcutaneous, 138, 143, 152, 173, 187 Sublingual, 45, 100, 187 Submucous, 100, 187 Subspecies, 185, 187 Substance P, 154, 168, 180, 183, 187 Substrate, 159, 187 Subungual, 43, 187 Sunburn, 94, 123, 187, 190 Supplementation, 67, 187 Suppression, 92, 187 Suppressive, 84, 187 Suramin, 55, 187 Sweat, 150, 187 Sweat Glands, 150, 187 Symphysis, 145, 178, 187 Symptomatic, 88, 187 Symptomatic treatment, 88, 187 Synergistic, 152, 187 Syphilis, 39, 187 Systemic, 6, 10, 80, 84, 99, 101, 108 Systemic disease, 99, 161, 187 Systemic therapy, 6, 187 T Telangiectasia, 117, 187 Temporal, 167, 188 Teratogenic, 154, 164, 188, 189 Tetracycline, 169, 188 Thalamic, 140, 188 Thalamic Diseases, 140, 188 Therapeutics, 29, 108, 188 Thermal, 85, 151, 170, 176, 188 Threonine, 184, 188 Thrombin, 175, 178, 188 Thrombomodulin, 178, 188 Thrombosis, 163, 178, 186, 188 Thrush, 100, 188 Thyroid, 100, 161, 188 Thyrotropin, 161, 188 Tin, 96, 188 Tinnitus, 172, 188 Tissue Culture, 11, 188 Topical chemotherapy, 96, 189 Toxic, iv, 6, 13, 69, 83, 84, 89, 100, 149, 152, 153, 161, 170, 176, 179, 189 Toxicity, 68, 69, 80, 84, 151, 189 Toxicology, 68, 69, 114, 189 Toxins, 138, 153, 162, 189 Trace element, 142, 188, 189 Trachea, 143, 165, 174, 188, 189

204

Keratosis

Tracheostomy, 10, 189 Transduction, 8, 189 Transfection, 142, 157, 189 Transfusion, 189 Translational, 10, 189 Translocation, 40, 154, 189 Trauma, 100, 141, 153, 161, 188, 189 Tremor, 117, 189 Tretinoin, 86, 87, 108, 189 Trichloroacetic Acid, 86, 96, 189 Trypanosomiasis, 187, 189 Tryptophan, 146, 189 Tuberous Sclerosis, 93, 117, 190 Tubulin, 168, 190 Tumor marker, 142, 190 Tumor suppressor gene, 173, 190 Tunica, 169, 190 U Ulcer, 91, 92, 94, 100, 149, 190 Ulceration, 149, 190 Ultraviolet radiation, 94, 187, 190 Unconscious, 149, 161, 190 Urea, 82, 95, 172, 187, 190 Urethra, 178, 190 Urinary, 157, 190 Urine, 142, 150, 159, 165, 190 Urogenital, 157, 190 Urticaria, 92, 100, 190 Uterus, 135, 145, 177, 190, 191 V Vaccination, 124, 190 Vaccine, 97, 124, 135, 191 Vaccine adjuvant, 97, 191 Vacuoles, 172, 191 Vagina, 10, 145, 191 Vascular, 58, 63, 136, 138, 145, 150, 153, 162, 171, 190, 191 Vasculitis, 176, 191

Vasodilators, 171, 191 Vector, 8, 173, 189, 191 Vein, 163, 173, 191 Venereal, 187, 191 Venous, 93, 178, 191 Verruca, 18, 93, 191 Vertebral, 141, 175, 191 Vertigo, 172, 191 Vesicular, 100, 159, 184, 191 Veterinary Medicine, 113, 191 Viral, 36, 80, 85, 100, 148, 171, 189, 191 Virulence, 189, 191 Virus, 8, 20, 28, 86, 89, 141, 157, 160, 175, 182, 184, 189, 191 Visual field, 181, 191 Vitiligo, 96, 179, 191 Vitro, 8, 9, 14, 38, 191 Vivo, 4, 5, 6, 7, 8, 14, 191 Vocal cord, 35, 191 Vulgaris, 6, 12, 87, 88, 92, 93, 135, 192 W War, 116, 192 Wart, 85, 164, 192 White blood cell, 138, 162, 166, 167, 169, 170, 175, 192 Windpipe, 174, 188, 192 Withdrawal, 84, 192 Wound Healing, 24, 80, 144, 146, 156, 163, 167, 192 X Xenograft, 138, 192 Xerostomia, 100, 192 X-ray, 75, 94, 96, 164, 169, 180, 192 X-ray therapy, 164, 192 Y Yeasts, 156, 174, 192 Z Zymogen, 178, 192

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