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

HYPERPIGMENTATION A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET R...

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HYPERPIGMENTATION

A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

HYPERPIGMENTATION 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., 1960Hyperpigmentation: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00571-9 1. Hyperpigmentation-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 hyperpigmentation. 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 HYPERPIGMENTATION.............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hyperpigmentation ....................................................................... 7 The National Library of Medicine: PubMed ................................................................................ 12 CHAPTER 2. NUTRITION AND HYPERPIGMENTATION .................................................................... 55 Overview...................................................................................................................................... 55 Finding Nutrition Studies on Hyperpigmentation...................................................................... 55 Federal Resources on Nutrition ................................................................................................... 56 Additional Web Resources ........................................................................................................... 56 CHAPTER 3. ALTERNATIVE MEDICINE AND HYPERPIGMENTATION ............................................. 59 Overview...................................................................................................................................... 59 National Center for Complementary and Alternative Medicine.................................................. 59 Additional Web Resources ........................................................................................................... 65 General References ....................................................................................................................... 66 CHAPTER 4. PATENTS ON HYPERPIGMENTATION .......................................................................... 67 Overview...................................................................................................................................... 67 Patents on Hyperpigmentation .................................................................................................... 67 Patent Applications on Hyperpigmentation ................................................................................ 74 Keeping Current .......................................................................................................................... 81 CHAPTER 5. BOOKS ON HYPERPIGMENTATION .............................................................................. 83 Overview...................................................................................................................................... 83 Book Summaries: Federal Agencies.............................................................................................. 83 Chapters on Hyperpigmentation.................................................................................................. 84 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 91 Overview...................................................................................................................................... 91 NIH Guidelines............................................................................................................................ 91 NIH Databases............................................................................................................................. 93 Other Commercial Databases....................................................................................................... 95 APPENDIX B. PATIENT RESOURCES ................................................................................................. 97 Overview...................................................................................................................................... 97 Patient Guideline Sources............................................................................................................ 97 Finding Associations.................................................................................................................... 99 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 101 Overview.................................................................................................................................... 101 Preparation................................................................................................................................. 101 Finding a Local Medical Library................................................................................................ 101 Medical Libraries in the U.S. and Canada ................................................................................. 101 ONLINE GLOSSARIES................................................................................................................ 107 Online Dictionary Directories ................................................................................................... 107 HYPERPIGMENTATION DICTIONARY ................................................................................ 109 INDEX .............................................................................................................................................. 161

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hyperpigmentation, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “hyperpigmentation” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Hereditary Hemochromatosis: Early Detection of a Common Yet Elusive Disease Source: Consultant. 42(2): 237-249. February 2002. Contact: Available from Cliggott Publishing Company. 330 Boston Post Road, Darien, CT 06820-4027. (203) 661-0600. Summary: About 1 in 200 persons in certain populations of northern Europe descent has hereditary hemochromatosis. Persons with this disease are predisposed to absorb excess iron from the gastrointestinal tract; the excess iron deposits in the organs (including the liver) and produces clinical symptoms including diabetes, cirrhosis (liver scarring) and heart failure. This article discusses the early detection of this common, yet elusive, disease. The three most common symptoms are fatigue, arthralgia (pain in the joints),

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and libido (sex drive) loss. Radiographic (x ray) findings can mimic those of osteoarthritis (OA); however, OA in unusual sites, in large non-weightbearing joints, or in a patient younger than 50 years can be clues to hereditary hemochromatosis. Diabetes develops in about 50 percent of affect patients, but the well known finding of bronze diabetes (skin hyperpigmentation) occurs late in the disease. The first phenotypic expression of hereditary hemochromatosis is an elevated transferrin saturation (TS). When fasting TS is greater than 45 percent, patients should have tests for serum ferritin levels, liver function, and genetic testing for the mutations associated with hemochromatosis (C282Y and H63D). Liver biopsy can help differentiate between hereditary hemochromatosis and other causes of liver disease. However, genetic testing may obviate the need for liver biopsy in selected cases. Treatment consists of dietary restrictions and therapeutic phelobotomy (blood removal) to keep ferritin levels low. First degree adult relatives of patients with hereditary hemochromatosis should also undergo screening for the condition. The article includes a patient care algorithm. 3 figures. 1 table. 7 references. •

Oral Manifestations of HIV Disease: An Update Source: Seminars in Cutaneous Medicine and Surgery. 16(4): 257-264. December 1997. Summary: More than 40 different oral diseases and conditions have been described in patients infected with human immunodeficiency virus (HIV). The recognition of the oral manifestations of HIV disease is of great significance because they may represent the first signs of the disease and have been shown to be highly predictive markers of severe immune deterioration and disease progression. This article reviews the spectrum of oral manifestations of HIV disease, with an emphasis on clinical recognition, diagnosis, and treatment. Sections include fungal infections, viral infections, bacterial infections, neoplasms, and miscellaneous HIV-related lesions, including those due to xerostomia (dry mouth), recurrent aphthous stomatitis, and melanotic hyperpigmentation of the oral mucosa. The author notes that although some oral diseases and conditions have a weak association with HIV disease, others are strongly linked with the disorder, and a few are AIDS-defining in nature. The author concludes that oral manifestations continue to play a central role in the diagnosis of the disease. A comprehensive oral examination of HIV-infected individuals may have a profound impact on long-term patient survival because of the increased likelihood of earlier diagnosis and institution of therapy.

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Hemochromatosis: It's More Than Skin-deep Source: Postgraduate Medicine. 91(4): 137-138, 140, 145. March 1992. Summary: The article explains that in a patient with hemochromatosis, excess iron is deposited in parenchymal tissue. Skin hyperpigmentation and damage to organs, including the liver and heart, often result. In this article, the author describes a case in which diagnosis was made by laboratory testing and examination of liver biopsy specimens. Appropriate therapy led to rapid improvement in the patient's condition. The author cautions that, because hemochromatosis may be inherited, family members of patients should be examined. 6 references. (AA).

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Recognition and Management of Hereditary Hemochromatosis Source: American Family Physician. 65(5): 853-860. March 1, 2002. Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237.

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Summary: This article addresses the recognition and management of hereditary hemochromatosis, the most common single-gene disorder in people of northern European descent. Hereditary hemochromatosis is characterized by increased intestinal absorption of iron, with deposition of the iron in multiple organs, including the liver. Previously, the classic description was combined diabetes mellitus, cutaneous hyperpigmentation (discoloring of the skin, usually to bronze), and cirrhosis (liver scarring). Increasingly, however, hereditary hemochromatosis is being diagnosed at an earlier, less symptomatic stage. The diagnosis is based on a combination of clinical, laboratory and pathologic findings, including elevated serum transferrin saturation. Life expectancy is usually normal if phlebotomy is initiated before the development of cirrhosis or diabetes mellitus. Hereditary hemochromatosis is associated with mutations in the HFE gene. Between 60 and 93 percent of patients with the disorder are homozygous for a mutation designated C282Y. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations, and resolving ambiguities concerning iron overload. 3 figures. 5 tables. 34 references. •

Oral Lesions of Iatrogenic and Undefined Etiology and Neurologic Disorders Associated with HIV Infection Source: Oral Surgery, Oral Medicine, Oral Pathology. 73(2): 201-211. February 1992. Summary: This article presents a review of oral lesions of iatrogenic and undefined etiology and neurologic disorders associated with human immunodeficiency virus (HIV) infection. The author focuses on mechanisms of pathogenesis, including possible common pathways and relationships to underlying immunosuppression. Conditions discussed include oral and gastrointestinal ulcers, skin rash, melanotic oral hyperpigmentation, neurologic disorders (opportunistic infections, tumors, and HIVrelated diseases), toxic epidermolysis, delayed wound healing, HIV-related thrombocytopenia, Reiter's syndrome, epithelioid angiomatosis, HIV-related salivary gland diseases, cystic intraparotid lymphadenopathy, and xerostomia. The author emphasizes that improved understanding and recognition of the clinical spectrum of these oral mucosal lesions will lead to improved patient care and a better knowledge of the pathophysiology of these disorders. 12 figures. 4 tables. 111 references. (AA-M).

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Non-Insulin-Dependent Diabetes Mellitus in Childhood and Adolescence Source: Pediatric Clinics of North America. 44(2): 307-337. April 1997. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article provides information about noninsulin-dependent diabetes mellitus (NIDDM, or Type II) in childhood and adolescence. While NIDDM in children may be associated with mitochondrial mutations, insulin-resistance syndromes, and structurally abnormal insulins, recent investigations have shown that children and adolescents can develop a form of NIDDM similar to that seen most frequently in adults. According to the author, this disorder seems to be most common among children of ethnic minority populations in the United States and may be increasing in prevalence because of increases in the prevalence of obesity among these groups. NIDDM has previously been reported to account for 2 to 3 percent of all pediatric patients with diabetes mellitus. Aside from ethnic risk factors and obesity, characteristics that increase the likelihood of development of NIDDM include family history and the presence of acanthosis nigricans (dermatologic condition which consists of hyperpigmentation with

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thickening of the skin into velvety, irregular folds in flexural or apposed areas) on physical examination. Topics include definition and diagnosis of NIDDM; epidemiology; pathophysiology of NIDDM; early-onset classic NIDDM; and therapy. Weight control through diet and exercise, oral hypoglycemic agents, and insulin are among the therapeutic options for NIDDM. The article notes that dietary and exercise regimens are often recommended as the initial therapeutic approach, with progression to oral hypoglycemic agents and finally insulin if hyperglycemia remains uncontrolled. Because children are often asymptomatic at the time of diagnosis, screening for NIDDM in high-risk populations is important. 3 figures. 1 table. 341 references. (AA-M). •

Management of Hemochromatosis Source: Annals of Internal Medicine. 129(11): 932-938. December 1, 1998. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: This article reviews how the complications of iron overload in hemochromatosis (an inherited propensity to absorb excess iron) can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy (blood removal) is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 micrograms per liter or more, and in women with serum ferritin levels of 200 micrograms per liter or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of removal of 1 unit of blood weekly until the serum feritin level is 10 to 20 micrograms per liter; and maintenance of the serum ferritin level at 50 micrograms per liter or less thereafter by periodic removal of blood. Hyperferritinemia (too much iron in the blood) attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis (liver scarring), primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrine abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation, reduce retention of nonferrous metals, and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity. 4 tables. 86 references.

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Drugs and Oral Disorders Source: Periodontology 2000. Volume 18: 21-36. October 1998. Contact: Available from Munksgaard International Publishers Ltd. Commerce Place, 350 Main Street, Malden, MA 02148-5018. (781) 388-8273. Fax (781) 388-8274. Summary: This article reviews the role of drugs as causal factors in oral diseases and disorders. The author stresses that the dental practitioner should maintain a high level of suspicion concerning the possibility that medications play a role when patients present with unexplained oral mucositis or other oral lesions. Topics include drug

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induced xerostomia (dry mouth), drugs that alter host resistance, the effects of tobacco products, drug induced gingival (gum tissues) overgrowth (anticonvulsive agents, cyclosporine, calcium channel blockers, sex hormones, cannibis, erythromycin), myelosuppression and agranulocytosis, drugs with direct effects on oral tissues (toxic irritants, drug allergies, erythema multiforme, fixed drug eruptions, oral contact allergy, lichenoid drug reactions, orofacial granulomatosis), and oral hyperpigmentation. The author concludes that drugs and medicaments may have a profound effect on the periodontal structures. In some instances, such as drug induced melanosis, the effect may be insignificant to the health of the patient. In other circumstances, drug induced disorders may initiate painful, destructive disease processes that will not be successfully managed unless the causal role of drugs is recognized and altered. Finally, the clinician must remain aware of the contribution of drug induced xerostomia and smoking to increased susceptibility to dental and periodontal diseases. 17 figures. 171 references. (AA-M).

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

Project Title: ARSENIC INDUCED SIGNALING PATHWAYS IN HUMAN EPIDERMIS Principal Investigator & Institution: Abdel-Malek, Zalfa A.; Research Professor; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002 Summary: (Taken from application) Toxicity due to exposure to high levels of arsenic through dietary, occupational, or medicinal routes has been well documented in different countries. The most obvious and prevalent manifestations of arsenic toxicity are the cutaneous changes that involve hyperkeratosis and increased pigmentation, and latent basal and squamous cell carcinoma. The latter two types of skin cancer differ from the sun induced skin cancer tumors in that they occur mainly on the palms and soles, rather than on sun exposed anatomical sites, and are more invasive and metastatic. Although arsenic induced cutaneous alterations are histologically well characterized,

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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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the molecular mechanisms by which they arise are poorly understood. In particular, the mechanisms by which arsenic affects genomic DNA and induces the expression or suppression of specific genes are for the most part unknown. Given that the skin is the first interface between the human body and the environment, and that cutaneous manifestations often reflect internal organ dysfunction, it is important to elucidate the mechanism of action of arsenic on human skin. There is sufficient evidence to support the notion that arsenic induces oxidative stress in mammalian cells. In the cutaneous epidermis, increased keratinocyte proliferation that leads to hyperkeratosis and eventually cancer tumors, as well as hyperpigmentation, may be the outcome of arsenic induced oxidative stress in keratinocytes and melanocytes, respectively. We are proposing to investigate the hypothesis that arsenic induced cutaneous alterations result from oxidative stress that disrupts normal epidermal cell proliferation and differentiation. For this, we will use primary cultures of normal human melanocytes and keratinocytes, as well as a skin substitute model that mimics the skin in situ. The effects of arsenic on genes involved in regulating keratinocyte proliferation and differentiation, and melanocyte pigmentation will be elucidated. The above in vitro models represent an optimal approach to elucidate the mechanism of action of arsenic on human cells and tissues. The results to be obtained should be relevant to other epithelial tissues, such as lung and bladder tissues, that are affected by arsenic. The studies hereby proposed should set the stage for further investigations of the mechanisms by which arsenic might promote the effects of other environmental carcinogens, such as ultraviolet radiation and polycyclic aromatic hydrocarbons. The outcome of this proposal should lead to more effective means for intervening in, and treating the manifestations of arsenic toxicity, and for setting more effective policies regarding safe levels of arsenic exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR PROTEIN MATURATION AND DEGRADATION Principal Investigator & Institution: Hebert, Daniel N.; Associate Professor; Biochem and Molecular Biology; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-JAN-2004 Summary: The overall goal of this proposal is to understand the biological processes involved in the protein folding, quality control and degradation of the membrane glycoprotein tyrosinase. Tyrosinase is a melanocyte-specific enzyme required for melanin synthesis. Mutations in tyrosinase is a melanocyte-specific enzyme required for melanin synthesis. Mutations in tyrosinase are the cause of tyrosinase-negative albinism. Many of these mutated forms contain amino acid substitution that have the potential to reduce the efficiency of proper folding and to cause retention in the endoplasmic reticulum (ER), the site of protein maturation for membrane glycoproteins. The key role of the ER in the regulation of tyrosine has been demonstrated in a melanotic melanoma cells in which ER-retention of wild type tyrosinase leads to subsequent degradation by the cytosolic ubiquitin-dependent proteasomal pathway. Understanding the mechanisms involved in tyrosinase biosynthesis and degradation will help us to address the following fundamental questions: Are the tyrosinase-mutants in albino melanocytes retained in the ER? What is the mechanism of retention? Can this retention be relieved to produce a correctly localized and functional protein? Can this retention by selectively implemented? The specific aims of this proposal are: 1) To analyze the protein maturation (folding, co- and post-translational modification, and chaperone binding) of wild type and mutant forms of tyrosinase in a cell-free maturation system. 2) To constitute the ER- retention/degradation pathway of tyrosinase in a cell-free system,

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identify and characterize the proteins involved in both the sorting and degradation processes. 3) To characterize the maturation, quality control and degradation of tyrosinase in normal and malignant melanocytes. These studies will provide insights into the maturation, quality control and degradation mechanisms of tyrosinase and the etiology of pigmentation-related diseases. In addition, a better understanding of the biosynthetic and degradation processes of the cell would assist in the design of therapeutic drugs targeted against genetic diseases caused by trafficking and ER maturation defects in general, and albinism and/or hypo- and hyperpigmentation in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL BASIS INVESTIGATIONS INTO MLS/LEOPARD SYNDROME Principal Investigator & Institution: Pacheco, Theresa R.; Dermatology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 29-JUN-2008 Summary: Lentigines are common pigmentary by hyperpigmentation secondary to an increased number of melanocytes. Multiple Lentigines Syndrome (MLS) is an inherited disease that results in generalized lentigines. Other manifestations of MLS may include developmental, auditory, and cardiovascular abnormalities. MLS is associated with skin findings phenotypically similar to those in the LEOPARD syndrome (MIM 151100). The clinical manifestations, which encompass the LEOPARD syndrome, include: Lentigines, ECG abnormalities, Ocular hypertelorism/Obstructive cardiomyopathy, Pulmonary valve stenosis, Abnormalities of genitalia in males, Retardation of growth, and Deafness. MLS also belongs to a group of genetic syndromes, the lentiginoses disorders. In these disorders, cutaneous abnormalities, such as lentigines, and non-cutaneous abnormalities, such as familial neoplasias and diverse developmental defects, manifest on a shared but variable basis. No clinical research studies on MLS or LEOPARD syndrome have been conducted. Neither the full extent of the clinical disease nor the basic cause of the disease is known. This proposal seeks support to train a young investigator in patient-oriented research. The proposal is a three-phase study of Multiple Lentigines Syndrome (MLS): genomics, clinical investigation, and diadactic study. If the proposal is funded, then the investigator: (i) will pursue a molecular basis for the Multiple Lentigines Syndrome (MLS) and will investigate whether a molecular link exists between MLS and LEOPARD Syndrome; (ii) will investigate whether a relationship exists between MLS and common pigmentation anomalies and, if so, whether this research can be used as the basis for new diagnostic and therapeutic methodologies, and (iii) will pursue extensive coursework in research and medical ethics; and will obtain experience with health sciences research, human genetics, molecular and cellular biological techniques, biostatistics, and clinical center regulations. Theresa Pacheco, M.D. is an Assistant Professor of Dermatology and is committed to a career in clinical research with an focus on molecular markers of disease (pigmentation anomalies) and patient-oriented research topics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NON-INVASIVE MEASUREMENT OF RPE LIPOFUSCIN Principal Investigator & Institution: Delori, Francois C.; Senior Scientist/Associate Professor; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 30-JUN-2006

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Summary: (provided by applicant): A major cause of blindness in older adults is agerelated macular degeneration (AMD). Its hallmarks are neovascularization and/or atrophy of photoreceptors and retinal pigment epithelial cells (RPE). The retina shows numerous changes prior to the development of atrophy, and at that stage individuals are considered to have age-related maculopathy (ARM). The long-term goal of this research is to accurately predict which individuals are at greatest risk for developing AMD. Our immediate goals are to use advanced biophysical techniques to test the hypothesis that high lipofuscin (accumulation of by-products of phagocytosis in RPE cells) is either a marker, or the cause, of advancing cell death. Specifically we will: (1) Test the hypothesis that the combined measurements of lipofuscin and Bruch's membrane deposits provide information that can ultimately be used to identify ARM patients at risk for more severe disease. To achieve this, we will compare the amounts of lipofuscin and Bruch's membrane deposits in older subjects with normal retinal status, subjects with bilateral ARM, and those with ARM in one eye and AMD (atrophy or neovascularization) in the other, and follow the patients to see if the those who have elevated levels of both lipofuscin and deposits progress to AMD. (2) Determine whether patients with ARM have significantly lower level of macular pigment and/or a different spatial distribution than age-matched normal controls. Since macular pigment is hypothesized to reduce oxidative damage to photoreceptors, determine whether there is a significant inverse relationship between macular pigment and RPE lipofuscin. (3) Examine evidence for genetic regulation of the accumulation of lipofuscin and/or macular pigment in monozygotic and dizygotic twins. (4) In longitudinal studies, determine whether the foci of elevated lipofuscin and/or its average level around borders of geographic atrophy correlate with rate or direction of greatest progression of subsequent atrophy, and whether discrete foci of hyperpigmentation consistently exhibit lipofuscin spectra. The proposed studies will provide needed data on relationships among AMD, lipofuscin and macular pigment, estimate genetic contribution to the latter, and assist identification of individuals at greatest risk for vision loss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: READING CENTER FOR AMD PREVENTION TRIAL Principal Investigator & Institution: Fine, Stuart L.; Professor & Chairman; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 07-DEC-1998; Project End 30-NOV-2003 Summary: The major long-term objective of the Reading Center for the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) is to provide reliable, systemic fundus grading and analysis of fundus features derived from photographic images of CAPT patients. This information will expand our current understanding of risk factors for vision loss associated with AMD as well as evaluate the potential efficacy of the CAPT in reducing the incidence of late complications of AMD. A variety of grading systems have been used to classify the presence and character of drusen and other clinical features of AMD. The majority of these systems utilize trained grading of stereoscopic color macular fundus photographs and fluorescein angiograms. The CAPT Reading Center System described in this proposal is a modification of the common system proposed by the International Classification and Grading System for AMD and the Wisconsin Age-related Maculopathy Grading System. 1,2 The Wisconsin System is currently used by the National Eye Institute sponsored Age-Related Eye Disease Study. Specific Aims: 1) To assess final CAPT eligibility and compliance with the CAPT treatment and retreatment protocols. 2) To monitor the immediate post-treatment and

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follow-up complications from stereoscopic color fundus photographs and fluorescein angiograms. 3) To grade, log and record specific baseline clinical features of AMD (for example, predominant drusen morphology drusen confluence, area of drusen involvement, focal hyperpigmentation, retinal pigment epithelial depigmentation, geographic atrophy. from stereoscopic fundus photographs grades using the CAPT Grading System. 4) To assess changes in drusen as a parameter for retreatment in the CAPT. In addition, to assess changes in other clinical features of AMD and to relate these changes and their baseline characteristics to the risk for late AMD complications, drusen regression and potentially protection from late AMD complications in treated eyes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF NA,K ATPASE BY THE AH RECEPTOR Principal Investigator & Institution: Walker, Mary K.; Associate Professor of Pharmacology And; None; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 05-AUG-2000; Project End 31-JUL-2004 Summary: Human exposure during pregnancy to persistent environmental pollutants, like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related chemicals, results in decreased birth weights, neurological deficits, thyroid hormone alterations, lung auscultation, and hyperpigmentation. The mechanism by which TCDD mediates developmental toxicity has not been elucidated. The basic helix-loop-helix-PAS transcription factor, aryl hydrocarbon receptor (AhR), is required for TCDD-induced teratogenicity in mice and likely mediates teratogenicity in other species. TCDD toxicity may result from alterations in gene transcription by the AhR. One potential AhR gene target that could account for some of TCDD's teratogenic effects is the Na+/K+ ATPase alpha1. Putative dioxin response elements are conserved in the 5' enhancer region of the mammalian and avian Na+/K+ ATPase alpha1 gene. In the chick embryo, TCDD reduces myocardial Na+/K+ ATPase alpha1 protein expression, induces a dilated cardiomyopathy, and alters ECGs, all consistent with reduced Na+/K+ ATPase activity. In mice lacking the AhR, embryos develop a hypertrophic cardiomyopathy and cardiac fibrosis which worsens with age, consistent with the potential overexpression of Na+/K+ ATPase alpha1 and development of hypertension. I will use the chick embryo and AhR null mice to test the hypothesis that the AhR regulates myocardial expression of the Na+/K+ ATPase alpha1 gene, altering cardiovascular development. The aims of this proposal are to (1) elucidate the regulation of myocardial Na+/K+ ATPase alpha1 gene in AhR null mice and in the developing chick embryo by TCDD using RT-PCR, and in vitro by promoter analysis of the avian gene; (2) determine the tissue significance of this regulation by quantitating myocardial ouabain binding sites and Na+/K+ ATPase enzyme activity in AhR null mice and TCDD-exposed chick embryos; (3) determine the functional significance by measuring blood pressure in AhR null mice and myocardial sensitivity to ouabain in TCDD-exposed chick embryos by ECG; and (4) analyze the expression of murine and avian homologues of candidates genes, whose expression is altered by TCDD in the rat embryo heart and lung as identified by Dr. Selmin, University of Arizona, by PCR-selected subtractive hybridization method and screening of gene microarrays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

12

Hyperpigmentation

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

A 14-week-old girl with severe respiratory distress, hyperpigmentation. Author(s): Listernick R. Source: Pediatric Annals. 2004 April; 33(4): 218-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101227

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A case of dark urine, hyperpigmentation and hepatomegaly. Author(s): McClements BM, McDowell IF, McCluskey DR. Source: Ir J Med Sci. 1988 May; 157(5): 157. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3225162

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A case of dermatomyositis presenting as localized hyperpigmentation of the hands and face. Author(s): Bottomley WW, Goodfield MD. Source: The British Journal of Dermatology. 1995 April; 132(4): 670-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7748767

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A case of skin hyperpigmentation due to alpha-MSH hypersecretion. Author(s): Pears JS, Jung RT, Bartlett W, Browning MC, Kenicer K, Thody AJ. Source: The British Journal of Dermatology. 1992 March; 126(3): 286-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1313279

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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 computer controlled scanner for the laser treatment of vascular lesions and hyperpigmentation. Author(s): Smithies DJ, Butler PH, Pickering JW, Walker EP. Source: Clinical Physics and Physiological Measurement : an Official Journal of the Hospital Physicists' Association, Deutsche Gesellschaft Fur Medizinische Physik and the European Federation of Organisations for Medical Physics. 1991 August; 12(3): 261-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1934913

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A girl with cutaneous hyperpigmentation, cafe au lait spots and ring chromosome 15 without significant deletion. Author(s): Morava E, Bartsch O, Czako M, Frensel A, Karteszi J, Kosztolanyi GY. Source: Genet Couns. 2003; 14(3): 337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14577679

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A new tool to eliminate hyperpigmentation in liposuction scars. Author(s): Gasperoni C, Salgarello M, Cimino A, Gasperoni P. Source: Annals of Plastic Surgery. 2000 August; 45(2): 214-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10949358

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A new type of minocycline-induced cutaneous hyperpigmentation. Author(s): Mouton RW, Jordaan HF, Schneider JW. Source: Clinical and Experimental Dermatology. 2004 January; 29(1): 8-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723711

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A patient with extensive stem cell factor-induced hyperpigmentation. Author(s): Bellet JS, Obadiah JM, Frothingham BM, Kurtzberg J, Grichnik JM. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 February; 71(2): 149-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635896

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A peculiar subphenotype in the fra(X) syndrome: extreme obesity-short staturestubby hands and feet-diffuse hyperpigmentation. Further evidence of disturbed hypothalamic function in the fra(X) syndrome? Author(s): Fryns JP, Haspeslagh M, Dereymaeker AM, Volcke P, Van den Berghe H. Source: Clinical Genetics. 1987 December; 32(6): 388-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3436088

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A probable mechanism for hyperpigmentation by fotemustine. Author(s): Schallreuter KU, Ring J. Source: Dermatology (Basel, Switzerland). 1992; 185(1): 76-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1638080

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A puzzling case of palpable hyperpigmentation. Polythelia, or supernumerary nipple. Author(s): Mishriki YY. Source: Postgraduate Medicine. 1998 December; 104(6): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9861260

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Absence of hyperpigmentation causes delay in the diagnosis of Addison's disease. Author(s): van 't Wout JW, Haak A. Source: The Netherlands Journal of Medicine. 1985; 28(5): 205-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4010838

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Acanthosis nigricans-like hyperpigmentation secondary to triazinate therapy. Author(s): Greenspan AH, Shupack JL, Foo SH, Wise AC. Source: Archives of Dermatology. 1985 February; 121(2): 232-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3977338

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Adrenal insufficiency secondary to hypothalamic corticotropin releasing factor (CRF) insufficiency with hyperpigmentation: a case report. Author(s): Fehm HL, Voigt KH, Lang R, Hetzel WD, Pfeiffer EF. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1976 November; 8(6): 470-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=187535

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Aloesin inhibits hyperpigmentation induced by UV radiation. Author(s): Choi S, Lee SK, Kim JE, Chung MH, Park YI. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 513-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372097

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An animal model for chlorpromazine-induced hyperpigmentation of the skin. Author(s): Forrest IS, Aber RC, Kosek JC, Serra MT. Source: Proc West Pharmacol Soc. 1969; 12: 36-40. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5812296

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An unusual case of non-malignant skin hyperpigmentation. Author(s): Potter AR. Source: British Medical Journal. 1979 December 22-29; 2(6205): 1628-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=534918

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Analysis of 54 cases of hypopigmentation and hyperpigmentation along the lines of Blaschko. Author(s): Nehal KS, PeBenito R, Orlow SJ. Source: Archives of Dermatology. 1996 October; 132(10): 1167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8859026

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Aplastic anaemia and reticulated skin hyperpigmentation. Author(s): Demiroglu H, Alikasifoglu M, Yalcin B, Dundar S. Source: Postgraduate Medical Journal. 1997 October; 73(864): 679-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9497993

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Asymptomatic progressive hyperpigmentation in a 16-year-old girl. Erythema dyschromicum perstans. Author(s): Nelson BR, Ramsey ML, Bruce S, Tschen JA, Knox JM. Source: Archives of Dermatology. 1988 May; 124(5): 769, 772. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3365000

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Atrophic pigmented dermatofibrosarcoma presenting as infraorbital hyperpigmentation. Author(s): Chuan MT, Tsai TF, Wu MC, Wong TH. Source: Dermatology (Basel, Switzerland). 1997; 194(1): 65-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9031796

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Azelaic acid 20% cream in the treatment of facial hyperpigmentation in darkerskinned patients. Author(s): Lowe NJ, Rizk D, Grimes P, Billips M, Pincus S. Source: Clinical Therapeutics. 1998 September-October; 20(5): 945-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9829446

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Azelaic acid and glycolic acid combination therapy for facial hyperpigmentation in darker-skinned patients: a clinical comparison with hydroquinone. Author(s): Kakita LS, Lowe NJ. Source: Clinical Therapeutics. 1998 September-October; 20(5): 960-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9829447

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Azidothymidine-induced hyperpigmentation mimicking primary adrenal insufficiency. Author(s): Merenich JA, Hannon RN, Gentry RH, Harrison SM. Source: The American Journal of Medicine. 1989 April; 86(4): 469-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2929632

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Azidothymidine-induced hyperpigmentation of skin and nails. Author(s): Bendick C, Rasokat H, Steigleder GK. Source: Archives of Dermatology. 1989 September; 125(9): 1285-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2774609

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Beta-melanocyte stimulating hormone levels in subjects with hyperpigmentation associated with megaloblastic anemia. Author(s): Baker SJ, Mathan VI, Abe K. Source: Blood. 1970 January; 35(1): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5412677

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Betaxolol-associated hyperpigmentation of the fingers in a patient with unrelated contact dermatitis. Author(s): Adams DR, Marks JG Jr. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 1997 September; 8(3): 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9249294

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Blue-gray discoloration of the face. Amiodarone-induced cutaneous hyperpigmentation. Author(s): Klein AD, Pardo RJ, Gould E, Kerdel F. Source: Archives of Dermatology. 1989 March; 125(3): 417, 420-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2923451

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Busulfan hyperpigmentation: light and electron microscopic studies. Author(s): Adam BA, Ismail R, Sivanesan S. Source: The Journal of Dermatology. 1980 December; 7(6): 405-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7026635

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Capecitabine induced cutaneous hyperpigmentation: report of a case. Author(s): Pui JC, Meehan S, Moskovits T. Source: J Drugs Dermatol. 2002 September; 1(2): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847748

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Case 47, part I: Oral hyperpigmentation. Author(s): Chuong R, Goldberg MH. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1983 September; 41(9): 613-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6577153

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Case 47, part II: Oral hyperpigmentation associated with Addison's disease. Author(s): Chuong R, Goldberg MH. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1983 October; 41(10): 680-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6225847

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Chemical and instrumental approaches to treat hyperpigmentation. Author(s): Briganti S, Camera E, Picardo M. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2003 April; 16(2): 101-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622786

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Chemical and pharmacologic agents that cause hyperpigmentation or hypopigmentation of the skin. Author(s): Lerner EA, Sober AJ. Source: Dermatologic Clinics. 1988 April; 6(2): 327-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3288388

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Chemotherapy-associated supravenous hyperpigmentation. Author(s): Baselga E, Drolet BA, Casper J, Esterly NB. Source: Dermatology (Basel, Switzerland). 1996; 192(4): 384-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8864385

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Chronic dermatitis and hyperpigmentation from petrolatum. Author(s): Maibach H. Source: Contact Dermatitis. 1978 February; 4(1): 62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=657795

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Chrysiasis: the role of sun exposure in dermal hyperpigmentation secondary to gold therapy. Author(s): Leonard PA, Moatamed F, Ward JR, Piepkorn MW, Adams EJ, Knibbe WP. Source: The Journal of Rheumatology. 1986 February; 13(1): 58-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3084781

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Clinical images: hydroxychloroquine-associated mucocutaneous hyperpigmentation. Author(s): True DG, Bryant LR, Harris MD, Bernert RA. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1698. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115210

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Clinical images: skin hyperpigmentation associated with minocycline therapy. Author(s): Kaplan H. Source: Arthritis and Rheumatism. 1997 July; 40(7): 1353. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9214437

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Coal-black hyperpigmentation at birth in a child with congenital adrenal hypoplasia. Author(s): Jones D, Kay M, Craigen W, McCabe E, Hawkins H, Dominey A. Source: Journal of the American Academy of Dermatology. 1995 August; 33(2 Pt 2): 3236. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7615878

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Cobalamin deficiency presenting with cutaneous hyperpigmentation: a report of two siblings. Author(s): Sabatino D, Kosuri S, Remollino A, Shotter B. Source: Pediatric Hematology and Oncology. 1998 September-October; 15(5): 447-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9783313

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Common hyperpigmentation disorders in adults: Part I. Diagnostic approach, cafe au lait macules, diffuse hyperpigmentation, sun exposure, and phototoxic reactions. Author(s): Stulberg DL, Clark N, Tovey D. Source: American Family Physician. 2003 November 15; 68(10): 1955-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655804

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Common hyperpigmentation disorders in adults: Part II. Melanoma, seborrheic keratoses, acanthosis nigricans, melasma, diabetic dermopathy, tinea versicolor, and postinflammatory hyperpigmentation. Author(s): Stulberg DL, Clark N, Tovey D. Source: American Family Physician. 2003 November 15; 68(10): 1963-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655805

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Cutaneous hyperpigmentation and polyglandular autoimmune syndrome type II. Author(s): Chung AD, English JC 3rd. Source: Cutis; Cutaneous Medicine for the Practitioner. 1997 February; 59(2): 77-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9040976

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Cutaneous hyperpigmentation caused by liposuction. Author(s): Mateu LP, Hernandez JJ. Source: Aesthetic Plastic Surgery. 1997 July-August; 21(4): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263542

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Cutaneous hyperpigmentation caused by systemic drugs. Author(s): Hendrix JD Jr, Greer KE. Source: International Journal of Dermatology. 1992 July; 31(7): 458-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1500233

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Cutaneous hyperpigmentation during therapy with hydroxychloroquine. Author(s): Millard TP, Kirk A, Ratnavel R. Source: Clinical and Experimental Dermatology. 2004 January; 29(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723734

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Cutaneous hyperpigmentation following venous sclerotherapy treated with deferoxamine mesylate. Author(s): Lopez L, Dilley RB, Henriquez JA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 September; 27(9): 795-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11553167

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Cutaneous hyperpigmentation induced by amiodarone hydrochloride. Author(s): Alinovi A, Reverberi C, Melissari M, Gabrielli M. Source: Journal of the American Academy of Dermatology. 1985 March; 12(3): 563-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3989014

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Cutaneous hyperpigmentation induced by doxycycline: histochemical and ultrastructural examination, laser microprobe mass analysis, and cathodoluminescence. Author(s): Bohm M, Schmidt PF, Lodding B, Uphoff H, Westermann G, Luger TA, Bonsmann G, Metze D. Source: The American Journal of Dermatopathology. 2002 August; 24(4): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12142617

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Cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. Etiology, prevention, and treatment. Author(s): Goldman MP, Sadick NS, Weiss RA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1995 January; 21(1): 19-29; Quiz 31-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7600016

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Delayed bleomycin-induced hyperpigmentation and pressure on the skin. Author(s): vonHilsheimer GE, Norton SA. Source: Journal of the American Academy of Dermatology. 2002 April; 46(4): 642-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907529

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Depigmenting and bleaching agents: coping with hyperpigmentation. Author(s): Katsambas AD, Stratigos AJ. Source: Clinics in Dermatology. 2001 July-August; 19(4): 483-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535393

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Diagnosis of lung carcinoid with cutaneous hyperpigmentation eight years after bilateral adrenalectomy. Author(s): Rodriguez Vaca MD, Angel M, Halperin I, Freixenet J, Marti M, Martinez Osaba MJ, Sanchez Lloret J, Palacin A, Vilardell E. Source: J Endocrinol Invest. 1987 December; 10(6): 537-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2831264

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Diffuse hyperpigmentation associated with acquired immunodeficiency syndrome. Author(s): Peter SA, Brignol YF, Razavi MH, Greeley N. Source: Journal of the National Medical Association. 1992 November; 84(11): 977-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1334155

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Diffuse hyperpigmentation in a man with diabetes. Author(s): Hariharan R, Fred HL. Source: Hosp Pract (Off Ed). 1996 November 15; 31(11): 45, 49. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8941160

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Diffuse hyperpigmentation of the skin: a clinicopathologic approach to diagnosis. Author(s): Stefanato CM, Bhawan J. Source: Semin Cutan Med Surg. 1997 March; 16(1): 61-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9125767

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Diffuse, progressive hyperpigmentation: an unusual skin manifestation of mycosis fungoides. Author(s): David M, Shanon A, Hazaz B, Sandbank M. Source: Journal of the American Academy of Dermatology. 1987 January; 16(1 Pt 2): 25760. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3819062

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Diltiazem-associated photodistributed hyperpigmentation: a review of 4 cases. Author(s): Scherschun L, Lee MW, Lim HW. Source: Archives of Dermatology. 2001 February; 137(2): 179-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11176690

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Diltiazem-induced hyperpigmentation in an African American woman. Author(s): Chawla A, Goyal S. Source: Journal of the American Academy of Dermatology. 2002 March; 46(3): 468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862194

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Diltiazem-induced photodistributed hyperpigmentation. Author(s): Boyer M, Katta R, Markus R. Source: Dermatology Online Journal [electronic Resource]. 2003 December; 9(5): 10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996383

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Disorders of hyperpigmentation. Author(s): Pandya AG, Guevara IL. Source: Dermatologic Clinics. 2000 January; 18(1): 91-8, Ix. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10626115

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Doxorubicin and hyperpigmentation. Author(s): Alagaratnam TT, Choi TK, Ong GB. Source: The Australian and New Zealand Journal of Surgery. 1982 October; 52(5): 531-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6959604

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Doxorubicin induced hyperpigmentation. Author(s): Kumar L, Kochupillai V. Source: N Z Med J. 1990 April 11; 103(887): 165. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2342686

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Doxorubicin-associated hyperpigmentation. Author(s): Curran CF. Source: N Z Med J. 1990 October 24; 103(900): 517. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2234654

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Drug- and heavy metal--induced hyperpigmentation. Author(s): Granstein RD, Sober AJ. Source: Journal of the American Academy of Dermatology. 1981 July; 5(1): 1-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6268671

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Drug-induced oral mucosal hyperpigmentation. Author(s): Scully C. Source: Primary Dental Care : Journal of the Faculty of General Dental Practitioners (Uk). 1997 January; 4(1): 35-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332345

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Duplication of 15q11.2-q14, including the P gene, in a woman with generalized skin hyperpigmentation. Author(s): Akahoshi K, Fukai K, Kato A, Kimiya S, Kubota T, Spritz RA. Source: American Journal of Medical Genetics. 2001 December 15; 104(4): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11754064

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Effect of pretreatment on the incidence of hyperpigmentation following cutaneous CO2 laser resurfacing. Author(s): West TB, Alster TS. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 January; 25(1): 15-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9935086

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Enhanced hyperpigmentation with combination chemotherapy. Author(s): Knobf MT, Kalm D. Source: Oncology Nursing Forum. 1990 September-October; 17(5): 762. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2251197

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Experience with a strong bleaching treatment for skin hyperpigmentation in Orientals. Author(s): Yoshimura K, Harii K, Aoyama T, Iga T. Source: Plastic and Reconstructive Surgery. 2000 March; 105(3): 1097-108; Discussion 1109-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10724272

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Extensive cutaneous hyperpigmentation caused by minocycline. Author(s): Pepine M, Flowers FP, Ramos-Caro FA. Source: Journal of the American Academy of Dermatology. 1993 February; 28(2 Pt 2): 292-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8436641

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Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene. Author(s): Maeyama H, Hidaka E, Ota H, Minami S, Kajiyama M, Kuraishi A, Mori H, Matsuda Y, Wada S, Sodeyama H, Nakata S, Kawamura N, Hata S, Watanabe M, Iijima Y, Katsuyama T. Source: Gastroenterology. 2001 January; 120(1): 210-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208730

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Familial multiforme ventricular extrasystoles with short stature, hyperpigmentation and microcephaly-a new syndrome. Author(s): Char F, Douglas JE, Dungan WT. Source: Birth Defects Orig Artic Ser. 1975; 11(5): 63-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1218236

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Familial progressive hyperpigmentation. Author(s): Chernosky ME, Anderson DE, Chang JP, Shaw MW, Romsdahl MM. Source: Archives of Dermatology. 1971 June; 103(6): 581-91 Passim. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4326548

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Familial progressive hyperpigmentation: a family study in China. Author(s): Ling DB, Lo T. Source: The British Journal of Dermatology. 1991 December; 125(6): 607. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1760373

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Familial spinocerebellar ataxia with skin hyperpigmentation. Author(s): Daras M, Tuchman AJ, David S. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1983 August; 46(8): 743-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6886718

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Fanconi's anemia. Tumor-like warts, hyperpigmentation associated with deranged keratinocytes, and depressed cell-mediated immunity. Author(s): Johansson E, Niemi KM, Siimes M, Pyrhonen S. Source: Archives of Dermatology. 1982 April; 118(4): 249-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6978105

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Flagellate hyperpigmentation following intralesional bleomycin treatment of verruca plantaris. Author(s): Abess A, Keel DM, Graham BS. Source: Archives of Dermatology. 2003 March; 139(3): 337-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622626

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Fluorescence photography in the evaluation of hyperpigmentation in photodamaged skin. Author(s): Kollias N, Gillies R, Cohen-Goihman C, Phillips SB, Muccini JA, Stiller MJ, Drake LA. Source: Journal of the American Academy of Dermatology. 1997 February; 36(2 Pt 1): 226-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039173

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Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. Author(s): Mori K, Ando I, Kukita A. Source: The Journal of Dermatology. 2001 May; 28(5): 282-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11436369

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Generalized hyperpigmentation with daunorubicin chemotherapy. Author(s): Kroumpouzos G, Travers R, Allan A. Source: Journal of the American Academy of Dermatology. 2002 February; 46(2 Suppl Case Reports): S1-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807454

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Generalized oral and cutaneous hyperpigmentation in Addison's disease. Author(s): Kim HW. Source: Odontostomatol Trop. 1988 September; 11(3): 87-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3268826

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Glycolic acid peels for postinflammatory hyperpigmentation in black patients. A comparative study. Author(s): Burns RL, Prevost-Blank PL, Lawry MA, Lawry TB, Faria DT, Fivenson DP. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1997 March; 23(3): 171-4; Discussion 175. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9145958

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Gustatory sweating associated with unilateral hyperpigmentation. Author(s): Weidman AI, Nathan D, Franks AG. Source: Archives of Dermatology. 1969 June; 99(6): 734-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5783087

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Histamine stimulates normal human melanocytes in vitro: one of the possible inducers of hyperpigmentation in urticaria pigmentosa. Author(s): Tomita Y, Maeda K, Tagami H. Source: Journal of Dermatological Science. 1993 October; 6(2): 146-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8274460

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How we do it: management of facial hyperpigmentation. Author(s): Ellis DA, Tan AK. Source: The Journal of Otolaryngology. 1997 August; 26(4): 286-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263903

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HPV 29-associated spotted hyperpigmentation of the face. Author(s): Jacobs S, Baron JM, Rubben A, Grussendorf-Conen EI. Source: European Journal of Dermatology : Ejd. 2002 March-April; 12(2): 189-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11872421

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Hyperkeratosis-hyperpigmentation syndrome: a confirmative case. Author(s): Figuera LE, Rodriguez-Catellanos MA, Gonzalez-Mendoza A, Cantu JM. Source: Clinical Genetics. 1993 February; 43(2): 73-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8448904

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Hyperpigmentation along tendons in progressive systemic sclerosis. Author(s): Sukenik S, Kleiner-Baumgarten A, Horowitz J. Source: The Journal of Rheumatology. 1986 April; 13(2): 474-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3723516

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Hyperpigmentation along the lines of Blaschko with associated chromosome 14 mosaicism. Author(s): Kuwahara RT, Henson T, Tunca Y, Wilroy SW. Source: Pediatric Dermatology. 2001 July-August; 18(4): 360-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584814

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Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 Ha-ras gene regulated by a mouse tyrosinase promoter. Author(s): Powell MB, Hyman P, Bell OD, Balmain A, Brown K, Alberts D, Bowden GT. Source: Molecular Carcinogenesis. 1995 February; 12(2): 82-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7662120

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Hyperpigmentation associated with selenium sulfide lotion. Author(s): Gillum RF. Source: Journal of the National Medical Association. 1996 September; 88(9): 551. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8855644

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Hyperpigmentation caused by hyperthyroidism: differences from the pigmentation of Addison's disease. Author(s): Banba K, Tanaka N, Fujioka A, Tajima S. Source: Clinical and Experimental Dermatology. 1999 May; 24(3): 196-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10354179

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Hyperpigmentation due to cyclosporin therapy. Author(s): Brady AJ, Wing AJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1989; 4(4): 309-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2502741

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Hyperpigmentation due to pyrimethamine use. Author(s): Ozturk R, Engin A, Ozaras R, Mert A, Tabak F, Aktuglu Y. Source: The Journal of Dermatology. 2002 July; 29(7): 443-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184645

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Hyperpigmentation due to topical calcipotriol and photochemotherapy in two psoriatic patients. Author(s): Glaser R, Rowert J, Mrowietz U. Source: The British Journal of Dermatology. 1998 July; 139(1): 148-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9764169

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Hyperpigmentation during interferon-alpha therapy for chronic hepatitis C virus infection. Author(s): Willems M, Munte K, Vrolijk JM, Den Hollander JC, Bohm M, Kemmeren MH, De Man RA, Brouwer JT. Source: The British Journal of Dermatology. 2003 August; 149(2): 390-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932249

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Hyperpigmentation following the use of bleaching creams. Localized exogenous ochronosis. Author(s): Connor T, Braunstein B. Source: Archives of Dermatology. 1987 January; 123(1): 105-6, 108. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3800410

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Hyperpigmentation following the use of Emla cream. Author(s): Godwin Y, Brotherston M. Source: British Journal of Plastic Surgery. 2001 January; 54(1): 82-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11121330

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Hyperpigmentation in a patient with AIDS, receiving rifabutin for disseminated Mycobacterium genavense infection. Author(s): Figueras C, Garcia L, Bertran JM. Source: European Journal of Pediatrics. 1998 July; 157(7): 612. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9686833

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Hyperpigmentation in a welder. Author(s): Markandeya N, Shenoi SD. Source: Contact Dermatitis. 2000 December; 43(6): 361. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11140390

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Hyperpigmentation in Chediak-Higashi syndrome. Author(s): Al-Khenaizan S. Source: Journal of the American Academy of Dermatology. 2003 November; 49(5 Suppl): S244-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576641

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Hyperpigmentation in Graves' disease. Author(s): Anania C, Rubenfeld S. Source: Thyroidology. 1989 December; 1(3): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2484875

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Hyperpigmentation in megaloblastic anemia. Author(s): Lee SH, Lee WS, Whang KC, Lee SJ, Chung JB. Source: International Journal of Dermatology. 1988 October; 27(8): 571-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3209318

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Hyperpigmentation in striae distensae after bleomycin treatment. Author(s): Tsuji T, Sawabe M. Source: Journal of the American Academy of Dermatology. 1993 March; 28(3): 503-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7680360

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Hyperpigmentation induced by furocoumarins. Author(s): Rodighiero G. Source: Farmaco [prat]. 1985 June; 40(6): 173-86. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4018247

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Hyperpigmentation induced by topical 5-aminolaevulinic acid plus visible light. Author(s): Monfrecola G, Procaccini EM, D'Onofrio D, Roberti G, Liuzzi R, Staibano S, Manco A, De Rosa G, Santoianni P. Source: Journal of Photochemistry and Photobiology. B, Biology. 2002 November; 68(23): 147-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12468210

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Hyperpigmentation induced by UVB at the application site of estradiol. Author(s): Claudy AL, Perrot JL. Source: Dermatologica. 1990; 181(2): 154-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2242785

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Hyperpigmentation mimicking Laugier syndrome, levodopa therapy and Addison's disease. Author(s): Vega Gutierrez J, Miranda Romero A, Martinez G, Torrero MV, Lopez de Juan M. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 May; 17(3): 324-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702077

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Hyperpigmentation of human skin grafted on to athymic nude mice: immunohistochemical study. Author(s): Matsumoto K, Robb E, Warden G, Nordlund J. Source: The British Journal of Dermatology. 1996 September; 135(3): 412-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8949435

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Hyperpigmentation of skin and nails in a patient with intestinal leiomyosarcoma. Author(s): Suda M, Ishii H, Kashiwazaki K, Tsuchiya M. Source: Digestive Diseases and Sciences. 1985 November; 30(11): 1108-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4053919

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Hyperpigmentation of the clavicular zone: a variant of friction melanosis. Author(s): Magana-Garcia M, Carrasco E, Herrera-Goepfert R, Pueblitz-Peredo S. Source: International Journal of Dermatology. 1989 March; 28(2): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2737806

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Hyperpigmentation of the distal phalanx in healthy Caucasian neonates. Author(s): Crespel E, Plantin P, Schoenlaub P, Blayo M, Queinnec C, Broussine L. Source: European Journal of Dermatology : Ejd. 2001 March-April; 11(2): 120-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11275807

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Hyperpigmentation of the flexures and pancytopenia during treatment with folate antagonists. Author(s): Jucgla A, Sais G, Berlanga J, Servitje O. Source: Acta Dermato-Venereologica. 1997 March; 77(2): 165-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9111840

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Hyperpigmentation of the lower extremities associated with porphyria cutanea tarda. Author(s): Held JL, Silvers DN, Grossman ME. Source: Archives of Dermatology. 1989 February; 125(2): 297-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2913968

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Hyperpigmentation of the nail from lead deposition. Author(s): Zhu WY, Xia MY, Huang SD, Du D. Source: International Journal of Dermatology. 1989 May; 28(4): 273-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2722344

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Hyperpigmentation of the skin along the thoracic and lumbar spine in progressive systemic sclerosis. Author(s): Sukenik S, Buskila D, Kleiner-Baumgarten A. Source: The Journal of Rheumatology. 1991 December; 18(12): 1946-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1795346

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Hyperpigmentation, bullae, and keratotic papules in a renal dialysis patient. Pseudoporphyria cutanea tarda (PPCT), acquired perforating disorder of renal dialysis (APD). Author(s): Ross M, White GM. Source: Archives of Dermatology. 1993 February; 129(2): 231, 234. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8094609

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Hyperpigmentation, neutrophilic alveolitis, and erythema nodosum resulting from minocycline. Author(s): Bridges AJ, Graziano FM, Calhoun W, Reizner GT. Source: Journal of the American Academy of Dermatology. 1990 May; 22(5 Pt 2): 959-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2335590

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Hyperpigmentation, vitiligo, and Addison's disease. Author(s): Mulligan TM, Sowers JR. Source: Cutis; Cutaneous Medicine for the Practitioner. 1985 October; 36(4): 317-8, 322. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2998703

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Hypomelanosis due to block of melanosomal maturation in amiodarone-induced hyperpigmentation. Author(s): Haas N, Schadendorf D, Hermes B, Henz BM. Source: Archives of Dermatology. 2001 April; 137(4): 513-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295949

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Identification of foreign metallic substances inducing hyperpigmentation of skin: light microscopy, electron microscopy and x-ray energy spectroscopic examination. Author(s): Bergfeld WF, McMahon JT. Source: Adv Dermatol. 1987; 2: 171-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3274957

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Idiopathic isolated perioral hyperpigmentation and treatment with the erbium:YAG laser. Author(s): Copcu E, Tugay C, Tugay G. Source: Lasers in Medical Science. 2004; 18(4): 223-6. Epub 2003 October 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15045606

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Imipramine hyperpigmentation: a slate-gray discoloration caused by long-term imipramine administration. Author(s): Hashimoto K, Joselow SA, Tye MJ. Source: Journal of the American Academy of Dermatology. 1991 August; 25(2 Pt 2): 35761. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1654344

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Imipramine-associated hyperpigmentation. Author(s): Dean CE, Grund FM. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 825-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773071

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Imipramine-induced hyperpigmentation: four cases and a review of the literature. Author(s): Ming ME, Bhawan J, Stefanato CM, McCalmont TH, Cohen LM. Source: Journal of the American Academy of Dermatology. 1999 February; 40(2 Pt 1): 159-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10025739

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Improvement of infraorbital hyperpigmentation following carbon dioxide laser resurfacing. Author(s): West TB, Alster TS. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1998 June; 24(6): 615-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9648566

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Induction of dramatic hyperpigmentation in a patient with generalized lichen planus treated with re-PUVA. Author(s): Carlin CS, Florell SR, Krueger GG. Source: Journal of Cutaneous Medicine and Surgery. 2002 March-April; 6(2): 125-7. Epub 2002 February 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992185

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Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser. Author(s): Taylor CR, Anderson RR. Source: J Dermatol Surg Oncol. 1994 September; 20(9): 592-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8089359

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Inflammatory acquired oral hyperpigmentation: association with melanophages demonstrating phenotypic characteristics of antigen presenting cells and activated monocytes. Author(s): James WD, Cooper KD, Todd RF 3rd, Brown C, Lewis D. Source: Journal of the American Academy of Dermatology. 1987 January; 16(1 Pt 2): 2206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3819056

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Isolated malabsorption of vitamin B12 causing megaloblastic anemia and hyperpigmentation in a Nigerian. Report of case. Author(s): Watson-Williams EJ, Fleming AF. Source: Blood. 1966 November; 28(5): 770-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5922681

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Laser treatment of imipramine-induced hyperpigmentation. Author(s): Atkin DH, Fitzpatrick RE. Source: Journal of the American Academy of Dermatology. 2000 July; 43(1 Pt 1): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10863228

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Latanoprost and hyperpigmentation of eyelashes. Author(s): Wand M. Source: Archives of Ophthalmology. 1997 September; 115(9): 1206-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9298071

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Letter: Acquired hypomelanosis: hyperpigmentation following reactions to hydroquinones. Author(s): Bentley-Phillips B, Bayles MA. Source: The British Journal of Dermatology. 1974 February; 90(2): 232-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4819141

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Letter: Hyperpigmentation after cancer chemotherapy. Author(s): O'Doherty CS. Source: Lancet. 1975 August 23; 2(7930): 365-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=51171

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Letter: Hyperpigmentation and folate deficiency. Author(s): Downham TF 2nd, Rehbein HM, Taylor KE. Source: Archives of Dermatology. 1976 April; 112(4): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1267476

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Letter: Hyperpigmentation caused by a fungicide. Author(s): Binder R. Source: Archives of Dermatology. 1976 June; 112(6): 880. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=942221

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Letter: Hyperpigmentation of nails from doxorubicin. Author(s): Pratt CB, Shanks EC. Source: Jama : the Journal of the American Medical Association. 1974 April 22; 228(4): 460. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4406195

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Letter: Hyperpigmentation of the upper part of the back. Author(s): Gerwels JW. Source: Archives of Dermatology. 1974 May; 109(5): 735. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4828542

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Letter: Serpentine supravenous fluorouracil hyperpigmentation. Author(s): Hrushesky WJ. Source: Jama : the Journal of the American Medical Association. 1976 July 12; 236(2): 138. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=947001

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Leukodystrophy, skin hyperpigmentation, and adrenal atrophy: SiemerlingCreutzfeldt disease. Transmission through several generations in two families. Author(s): Ropers HH, Burmeister P, Petrykowski W, Schindera F. Source: American Journal of Human Genetics. 1975 July; 27(4): 547-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=168769

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Lichen nitidus with hyperpigmentation. Author(s): van de Kerkhof PC. Source: The Journal of Dermatology. 1986 October; 13(5): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3546447

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Linear and whorled nevoid hypermelanosis associated with developmental delay and generalized convulsions. Author(s): Alrobaee AA, Alsaif F. Source: International Journal of Dermatology. 2004 February; 43(2): 145-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15125509

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Linear hyperpigmentation overlying veins in association with collagen vascular disease. Author(s): Werth VP, Schumacher HR Jr, Von Feldt JM. Source: Journal of the American Academy of Dermatology. 1993 December; 29(6): 103940. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8245241

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Linear hyperpigmentation with extensive epidermal apoptosis: a variant of linear lichen planus pigmentosus? Author(s): Akagi A, Ohnishi Y, Tajima S, Ishibashi A. Source: Journal of the American Academy of Dermatology. 2004 May; 50(5 Suppl): S7880. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15097934

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Linear hypopigmentation and hyperpigmentation, including mosaicism. Author(s): Loomis CA. Source: Semin Cutan Med Surg. 1997 March; 16(1): 44-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9125765

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Lingual hyperpigmentation associated with minocycline therapy. Author(s): Meyerson MA, Cohen PR, Hymes SR. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1995 February; 79(2): 180-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7614181

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Local expression and systemic release of stem cell factor in systemic sclerosis with diffuse hyperpigmentation. Author(s): Yamamoto T, Sawada Y, Katayama I, Nishioka K. Source: The British Journal of Dermatology. 2001 January; 144(1): 199-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167715

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Localized cisplatin hyperpigmentation induced by pressure. A case report. Author(s): Al-Lamki Z, Pearson P, Jaffe N. Source: Cancer. 1996 April 15; 77(8): 1578-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8608546

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Longitudinal, transverse, and diffuse nail hyperpigmentation induced by hydroxyurea. Author(s): Hernandez-Martin A, Ros-Forteza S, de Unamuno P. Source: Journal of the American Academy of Dermatology. 1999 August; 41(2 Pt 2): 3334. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10426924

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Long-term skin hyperpigmentation after electrocardiographic monitoring. Author(s): Sprung J, Schoenwald PK. Source: Journal of Clinical Anesthesia. 1997 November; 9(7): 602-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9347441

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Macular amyloidosis, presenting as periocular hyperpigmentation. Author(s): van den Berg WH, Starink TM. Source: Clinical and Experimental Dermatology. 1983 March; 8(2): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6851240

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Macular hyperpigmentation in a furnace worker. Author(s): Paul M, Shenoi SD, Srinivas CR. Source: Contact Dermatitis. 1998 March; 38(3): 184. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9536428

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Management of facial hyperpigmentation. Author(s): Perez-Bernal A, Munoz-Perez MA, Camacho F. Source: American Journal of Clinical Dermatology. 2000 September-October; 1(5): 261-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702317

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Mechanisms for hyperpigmentation in postinflammatory pigmentation, urticaria pigmentosa and sunburn. Author(s): Tomita Y, Maeda K, Tagami H. Source: Dermatologica. 1989; 179 Suppl 1: 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2550287

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Mechanisms for post-inflammatory hyperpigmentation and hypopigmentation. Author(s): Nordlund JJ, Abdel-Malek ZA. Source: Prog Clin Biol Res. 1988; 256: 219-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2835778

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Mechanisms of hyperpigmentation. Author(s): Sanchez NP, Sanchez JL, Vazquez-Botet M. Source: P R Health Sci J. 1986 December; 5(3): 123-32. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3550863

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Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies. Author(s): Breathnach AS. Source: Cutis; Cutaneous Medicine for the Practitioner. 1996 January; 57(1 Suppl): 36-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8654129

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Melanocanthoma: a rare cause of oral hyperpigmentation. Author(s): Chandler K, Chaudhry Z, Kumar N, Barrett AW, Porter SR. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1997 November; 84(5): 492-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9394380

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Melanonychia and mucocutaneous hyperpigmentation due to hydroxyurea use in an HIV-infected patient. Author(s): Laughon SK, Shinn LL, Nunley JR. Source: International Journal of Dermatology. 2000 December; 39(12): 928-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168664

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Metabolic acidosis in an Afro-Caribbean man with hyperpigmentation. Author(s): Darko DA, Chan NN, Jackson A, Peiris C, O'Shea D. Source: Postgraduate Medical Journal. 2000 July; 76(897): 429, 439-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10878209

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Metabolic studies of chlorpromazine induced hyperpigmentation of the skin in psychiatric patients. Author(s): Bolt AG, Forrest IS. Source: Agressologie. 1968 March-April; 9(2): 201-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5675487

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Methacycline hyperpigmentation: a five-year follow-up. Author(s): Moller H, Rausing A. Source: Acta Dermato-Venereologica. 1980; 60(6): 495-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6162334

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Methotrexate-induced hyperpigmentation in a rheumatoid arthritis patient. Author(s): Toussirot E, Wendling D. Source: Clin Exp Rheumatol. 1999 November-December; 17(6): 751. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10609080

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Minocycline hydrochloride hyperpigmentation complicating treatment of pyoderma gangrenosum. Author(s): Miralles ES, Nunez M, Perez B, Ledo A. Source: The Journal of Dermatology. 1994 December; 21(12): 965-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7868770

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Minocycline hydrochloride hyperpigmentation complicating treatment of venous ectasia of the extremities. Author(s): Leffell DJ. Source: Journal of the American Academy of Dermatology. 1991 March; 24(3): 501-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2061453

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Minocycline hyperpigmentation localized to the lips: an unusual fixed drug reaction? Author(s): Chu P, Van SL, Yen TS, Berger TG. Source: Journal of the American Academy of Dermatology. 1994 May; 30(5 Pt 1): 802-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8176028

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Minocycline hyperpigmentation: model for in situ phagocytic activity of factor XIIIa positive dermal dendrocytes. Author(s): Altman DA, Fivenson DP, Lee MW. Source: Journal of Cutaneous Pathology. 1992 August; 19(4): 340-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1358929

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Minocycline hyperpigmentation: skin, tooth, nail, and bone involvement. Author(s): Wolfe ID, Reichmister J. Source: Cutis; Cutaneous Medicine for the Practitioner. 1984 May; 33(5): 457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6478869

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Minocycline-induced cutaneous hyperpigmentation. Author(s): Joseph WS, Sabo MA. Source: Journal of the American Podiatric Medical Association. 2000 May; 90(5): 268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10833877

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Minocycline-induced hyperpigmentation in leprosy. Author(s): Fleming CJ, Hunt MJ, Salisbury EL, McCarthy SW, Barnetson RS. Source: The British Journal of Dermatology. 1996 April; 134(4): 784-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8733393

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Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid. Author(s): Ozog DM, Gogstetter DS, Scott G, Gaspari AA. Source: Archives of Dermatology. 2000 September; 136(9): 1133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987869

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Minocycline-induced hyperpigmentation of the tongue. Author(s): Tanzi EL, Hecker MS. Source: Archives of Dermatology. 2000 March; 136(3): 427-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10724219

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Minocycline-induced hyperpigmentation of the tongue: successful treatment with the Q-switched ruby laser. Author(s): Friedman IS, Shelton RM, Phelps RG. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 March; 28(3): 205-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896769

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Minocycline-induced hyperpigmentation. Author(s): Hung PH, Caldwell JB, James WD. Source: The Journal of Family Practice. 1995 August; 41(2): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7636458

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Minocycline-induced hyperpigmentation. Treatment with the neodymium:YAG laser. Author(s): Wilde JL, English JC 3rd, Finley EM. Source: Archives of Dermatology. 1997 November; 133(11): 1344-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9371014

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Minocycline-induced hyperpigmentation: treatment with the Q-switched Nd:YAG laser. Author(s): Greve B, Schonermark MP, Raulin C. Source: Lasers in Surgery and Medicine. 1998; 22(4): 223-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603284

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Minocycline-induced oral hyperpigmentation. Author(s): Eisen D. Source: Lancet. 1997 February 8; 349(9049): 400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9033473

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Minocycline-related cutaneous hyperpigmentation as demonstrated by light microscopy, electron microscopy and X-ray energy spectroscopy. Author(s): Argenyi ZB, Finelli L, Bergfeld WF, Tuthill RJ, McMahon JT, Ratz JL, Petroff N. Source: Journal of Cutaneous Pathology. 1987 June; 14(3): 176-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3611461

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Minocycline-related hyperpigmentation. Author(s): Basler RS. Source: Archives of Dermatology. 1985 May; 121(5): 606-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3158284

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Mitoxantrone induced hyperpigmentation. Author(s): Kumar L, Kochipillai V. Source: N Z Med J. 1990 February 14; 103(883): 55. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2304701

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Mucosal hyperpigmentation due to oxabolone. Author(s): Drago F, Gelati G, Battifoglio ML, Rebora A. Source: Acta Dermato-Venereologica. 1995 March; 75(2): 158. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7604652

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Mycosis fungoides with marked hyperpigmentation. Author(s): Kikuchi A, Shimizu H, Nishikawa T. Source: Dermatology (Basel, Switzerland). 1996; 192(4): 360-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8864376

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Myocardial disease. A case associated with hyperpigmentation and multifocal vascular sclerosis. Author(s): Arcasoy MM, Guntheroth WG, Smuckler E. Source: Am J Dis Child. 1968 October; 116(4): 434-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4235223

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Nail and mucocutaneous hyperpigmentation with azidothymidine therapy. Author(s): Greenberg RG, Berger TG. Source: Journal of the American Academy of Dermatology. 1990 February; 22(2 Pt 2): 327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2303586

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Nail and skin hyperpigmentation associated with hydroxyurea therapy for polycythemia vera. Author(s): Gropper CA, Don PC, Sadjadi MM. Source: International Journal of Dermatology. 1993 October; 32(10): 731-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8225715

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Nail hyperpigmentation secondary to therapy with doxorubicin. Author(s): Giacobetti R, Esterly NB, Morgan ER. Source: Am J Dis Child. 1981 April; 135(4): 317-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7211789

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Nelson's syndrome: another condition associated with mucocutaneous hyperpigmentation. Author(s): Moyer GN, Terezhalmy GT, O'Brian JT. Source: J Oral Med. 1985 January-March; 40(1): 13-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3855979

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Nevus spilus-like hyperpigmentation in psoriatic lesions during PUVA therapy. Author(s): Helland S, Bang G. Source: Acta Dermato-Venereologica. 1980; 60(1): 81-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6153845

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Newborns with ambiguous genitalia, impalpable gonads, and hyperpigmentation. Author(s): Chang HY, Lee YJ, Lin SP, Lee HH. Source: Acta Paediatr Taiwan. 2001 January-February; 42(1): 1-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11270178

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Observations and proposed mechanism of N,N',N''-triethylenethiophosphoramide (thiotepa)-induced hyperpigmentation. Author(s): Horn TD, Beveridge RA, Egorin MJ, Abeloff MD, Hood AF. Source: Archives of Dermatology. 1989 April; 125(4): 524-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2539058

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Oral hyperpigmentation and adrenocortical hypofunction in a patient with acquired immunodeficiency syndrome. Author(s): Porter SR, Glover S, Scully C. Source: Oral Surg Oral Med Oral Pathol. 1990 July; 70(1): 59-60. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2371052

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Oral hyperpigmentation and occult malignancy--report of a case. Author(s): Babin RW, Ceilley RI, DeSanto LW. Source: The Journal of Otolaryngology. 1978 October; 7(5): 389-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=739570

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Oral hyperpigmentation in HIV-infected patients. Author(s): Langford A, Pohle HD, Gelderblom H, Zhang X, Reichart PA. Source: Oral Surg Oral Med Oral Pathol. 1989 March; 67(3): 301-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2927925

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Oral mucosal hyperpigmentation secondary to antimalarial drug therapy. Author(s): Kleinegger CL, Hammond HL, Finkelstein MW. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2000 August; 90(2): 189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936838

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Pachyonychia congenita with cutaneous amyloidosis and hyperpigmentation--a distinct variant. Author(s): Tidman MJ, Wells RS, MacDonald DM. Source: Journal of the American Academy of Dermatology. 1987 May; 16(5 Pt 1): 935-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3584576

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Paraneoplastic hyperpigmentation secondary to lung cancer resolving after chemotherapy. Author(s): Ozguroglu M, Tahan V, Ozguroglu E, Ozaras R, Demir G. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1999 October; 22(5): 533-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10521074

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Periorbital hyperpigmentation and erythema dyschromicum perstans. Author(s): Ing EB, Buncic JR, Weiser BA, de Nanassy J, Boxall L. Source: Can J Ophthalmol. 1992 December; 27(7): 353-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1490247

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Periorbital hyperpigmentation. Author(s): Haddock N, Wilkin JK. Source: Jama : the Journal of the American Medical Association. 1981 August 21; 246(8): 835. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7253154

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Periorbital hyperpigmentation. An overlooked genetic disorder of pigmentation. Author(s): Goodman RM, Belcher RW. Source: Archives of Dermatology. 1969 August; 100(2): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5797956

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Periungal hyperpigmentation induced by cisplatin. Author(s): Kim KJ, Chang SE, Choi JH, Sung KJ, Moon KC, Koh JK. Source: Clinical and Experimental Dermatology. 2002 March; 27(2): 118-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952702

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Periungual hyperpigmentation mimicking Hutchinson's sign associated with minocycline administration. Author(s): Mooney E, Bennett RG. Source: J Dermatol Surg Oncol. 1988 September; 14(9): 1011-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3410999

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Photo quiz. Blue-gray centrofacial hyperpigmentation. Author(s): Rubegni P, de Aloe G, Maritati E, Mondillo S. Source: American Family Physician. 2001 April 1; 63(7): 1409-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11310653

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Photosensitivity and hyperpigmentation in amiodarone-treated patients: incidence, time course, and recovery. Author(s): Rappersberger K, Honigsmann H, Ortel B, Tanew A, Konrad K, Wolff K. Source: The Journal of Investigative Dermatology. 1989 August; 93(2): 201-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2754275

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Polyneuropathy, skin hyperpigmentation, edema, and hypertrichosis in localized osteosclerotic myeloma. Author(s): Iwashita H, Ohnishi A, Asada M, Kanazawa Y, Kuroiwa Y. Source: Neurology. 1977 July; 27(7): 675-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=559975

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Possible mechanisms of skin hyperpigmentation. Author(s): Flaxman BA. Source: Journal of the American Academy of Dermatology. 1999 December; 41(6): 1048. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10570400

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Post laser hyperpigmentation and occupational ultraviolet radiation exposure. Author(s): Munnoch DA, Gorst CM, Hancock K. Source: British Journal of Plastic Surgery. 2000 April; 53(3): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10738340

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Postinflammatory hyperpigmentation. Author(s): Epstein JH. Source: Clinics in Dermatology. 1989 April-June; 7(2): 55-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2667741

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Postinflammatory hyperpigmentation. Author(s): Nordlund JJ. Source: Dermatologic Clinics. 1988 April; 6(2): 185-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2454174

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Postinflammatory hypopigmentation and hyperpigmentation. Author(s): Ruiz-Maldonado R, Orozco-Covarrubias ML. Source: Semin Cutan Med Surg. 1997 March; 16(1): 36-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9125764

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Postsclerotherapy hyperpigmentation. Author(s): Anderson RR. Source: J Dermatol Surg Oncol. 1992 May; 18(5): 444. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1607469

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Postsclerotherapy hyperpigmentation. The role of serum ferritin levels and the effectiveness of treatment with the copper vapor laser. Author(s): Thibault P, Wlodarczyk J. Source: J Dermatol Surg Oncol. 1992 January; 18(1): 47-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1740567

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Postsclerotherapy hyperpigmentation. Treatment with a flashlamp-excited pulsed dye laser. Author(s): Goldman MP. Source: J Dermatol Surg Oncol. 1992 May; 18(5): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1607465

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Postsclerotherapy hyperpigmentation: a histologic evaluation. Author(s): Goldman MP, Kaplan RP, Duffy DM. Source: J Dermatol Surg Oncol. 1987 May; 13(5): 547-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3571692

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Pregnancy-associated hyperpigmentation: longitudinal melanonychia. Author(s): Fryer JM, Werth VP. Source: Journal of the American Academy of Dermatology. 1992 March; 26(3 Pt 2): 493-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1564158

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Primary disorders of hyperpigmentation. Author(s): Fulk CS. Source: Journal of the American Academy of Dermatology. 1984 January; 10(1): 1-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6420449

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Progressive cribriform and zosteriform hyperpigmentation. Author(s): Rower JM, Carr RD, Lowney ED. Source: Archives of Dermatology. 1978 January; 114(1): 98-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=619793

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Progressive cribriform and zosteriform hyperpigmentation: the late-onset feature of linear and whorled nevoid hypermelanosis associated with congenital neurological, skeletal and cutaneous anomalies. Author(s): Schepis C, Alberti A, Siragusa M, Romano C. Source: Dermatology (Basel, Switzerland). 1999; 199(1): 72-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10449967

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Progressive hyperpigmentation and generalized lentiginosis without associated systemic symptoms: a rare hereditary pigmentation disorder in south-east Germany. Author(s): Zanardo L, Stolz W, Schmitz G, Kaminski W, Vikkula M, Landthaler M, Vogt T. Source: Acta Dermato-Venereologica. 2004; 84(1): 57-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040480

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Progressive hyperpigmentation: case report with a clinical, histological, and ultrastructural investigation. Author(s): Betts CM, Bardazzi F, Fanti PA, Tosti A, Varotti C. Source: Dermatology (Basel, Switzerland). 1994; 189(4): 384-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7873826

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Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light. Author(s): Ho WS, Chan HH, Ying SY, Chan PC, Burd A, King WW. Source: Lasers in Surgery and Medicine. 2003; 32(1): 42-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516069

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Psychosis, dyskinesia, and hyperpigmentation. Author(s): Proctor P. Source: Lancet. 1971 May 22; 1(7708): 1069. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4102993

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Q-switched ruby laser treatment for postsclerotherapy hyperpigmentation. Author(s): Tafazzoli A, Rostan EF, Goldman MP. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 July; 26(7): 653-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10886273

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Q-switched ruby laser treatment of minocycline-induced cutaneous hyperpigmentation. Author(s): Knoell KA, Milgraum SS, Kutenplon M. Source: Archives of Dermatology. 1996 October; 132(10): 1251-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8859046

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Reactive lentiginous hyperpigmentation after cryosurgery for lentigo maligna. Author(s): Bohler-Sommeregger K, Schuller-Petrovic S, Knobler R, Neumann PR. Source: Journal of the American Academy of Dermatology. 1992 October; 27(4): 523-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1401302

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Red hair and hyperpigmentation in a black man after chemotherapy. Author(s): Loureiro C, Gill PS, Rarick M, Levine AM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1987 October; 5(10): 1705-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3655865

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Reticulate hyperpigmentation distributed in a zosteriform fashion. Author(s): Patrizi A, Di Lernia V, Varotti C. Source: The British Journal of Dermatology. 1989 August; 121(2): 280. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2775652

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Reticulate hyperpigmentation distributed in a zosteriform fashion: a new clinical type of hyperpigmentation. Author(s): Iijima S, Naito Y, Naito S, Uyeno K. Source: The British Journal of Dermatology. 1987 October; 117(4): 503-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3676095

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Reticulate hyperpigmentation of Iijima, Naito and Uyeno and other linear hyperpigmentations of children. Author(s): Di Lernia V, Patrizi A, Neri I, Varotti C. Source: Acta Dermato-Venereologica. 1992 September; 72(5): 393. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1361297

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Reticulate hyperpigmentation of Iijima, Naito and Uyeno. A European case. Author(s): Bjorngren H, Holst R. Source: Acta Dermato-Venereologica. 1991; 71(3): 248-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678231

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Reticulate hyperpigmentation of the skin after topical application of benzoyl peroxide. Author(s): Weinberg JM, Moss T, Gupta SM, White SM, Don PC. Source: Acta Dermato-Venereologica. 1998 July; 78(4): 301-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9689304

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Reticulate hyperpigmentation. Author(s): Schnur RE, Heymann WR. Source: Semin Cutan Med Surg. 1997 March; 16(1): 72-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9125768

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Reticulate nonmelanocytic hyperpigmentation anomaly. A probable variant of Dowling-Degos disease. Author(s): Oriba HA, Lo JS, Dijkstra JW, Bergfeld WF. Source: International Journal of Dermatology. 1991 January; 30(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1993563

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Reticulate postinflammatory hyperpigmentation with band-like mucin deposition. Author(s): Noto G, Pravata G, Arico M. Source: International Journal of Dermatology. 1998 November; 37(11): 829-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9865868

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Return of hyperpigmentation within a cafe-au-lait macule following treatment of vitiligo. Author(s): Schaffer JV, Bolognia JL, Watsky K. Source: Dermatology (Basel, Switzerland). 2000; 201(3): 283-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096214

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Reversible cutaneous hyperpigmentation in vitamin B12 deficiency. Author(s): Ahuja SR, Sharma RA. Source: Indian Pediatrics. 2003 February; 40(2): 170-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626837

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Reversible hyperpigmentation associated with high dose hydroxyurea. Author(s): Majumdar G, Heard SE, Slater NG. Source: Bmj (Clinical Research Ed.). 1990 June 2; 300(6737): 1468. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2379018

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Reversible hyperpigmentation of skin and nails with white hair due to vitamin B12 deficiency. Author(s): Noppakun N, Swasdikul D. Source: Archives of Dermatology. 1986 August; 122(8): 896-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3740873

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Rippled hyperpigmentation resembling macular amyloidosis--a feature of atopic eczema. Author(s): Hughes BR, Cunliffe WJ. Source: Clinical and Experimental Dermatology. 1990 September; 15(5): 380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2225545

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Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: the Blue Mountains Eye Study cohort. Author(s): Wang JJ, Foran S, Smith W, Mitchell P. Source: Archives of Ophthalmology. 2003 May; 121(5): 658-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742843

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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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Ruby laser treatment for hyperpigmentation after cytotoxic therapy for AIDS-related Kaposi's sarcoma. Author(s): Rudlinger R. Source: The British Journal of Dermatology. 1998 May; 138(5): 924-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9666861

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Ruby laser treatment of melasma and postinflammatory hyperpigmentation. Author(s): Kopera D, Hohenleutner U. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1995 November; 21(11): 994. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7582845

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Scleredema adultorum associated with a monoclonal gammopathy and generalized hyperpigmentation. Author(s): McFadden N, Ree K, Soyland E, Larsen TE. Source: Archives of Dermatology. 1987 May; 123(5): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3579342

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Serpentine supravenous 5-fluorouracil (NSC-19893) hyperpigmentation. Author(s): Hrushesky WJ. Source: Cancer Treat Rep. 1976 May; 60(5): 639. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=991154

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Serpentine supravenous hyperpigmentation induced by the nitrosourea fotemustine. Author(s): Claudy AL, Levigne V, Boucheron S. Source: Dermatology (Basel, Switzerland). 1992; 184(1): 70-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1559000

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Skeletal dysplasia, hyperpigmentation, cutis laxa, endocrine abnormality, and mental retardation--the Patterson syndrome. Author(s): David TJ. Source: Prog Clin Biol Res. 1982; 104: 331-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7163277

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Skin hyperpigmentation following removal of electrocardiogram pads. Author(s): Ortega R. Source: Anesthesiology. 1992 June; 76(6): 1063-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1599102

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Solar-induced postinflammatory hyperpigmentation after laser hair removal. Author(s): Hasan AT, Eaglstein W, Pardo RJ. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 February; 25(2): 113-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10037515

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Special selection: minocycline-induced hyperpigmentation of the tongue. Author(s): Tanzi EL, Hecker MS. Source: Archives of Family Medicine. 2000 August; 9(8): 687-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10927700

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Speckled hyperpigmentation, palmo-plantar punctate keratoses and childhood blistering: a clinical triad, with variable associations. A report of two families. Author(s): Boss JM, Matthews CN, Peachey RD, Summerly R. Source: The British Journal of Dermatology. 1981 November; 105(5): 579-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6457621

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Spontaneous hair hyperpigmentation in response to vitamin intake in pregnancy--a clue for homocystinuria. Author(s): Reish O, Berry SA, King RA. Source: American Journal of Obstetrics and Gynecology. 1995 November; 173(5): 1640-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7503225

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Supravenous hyperpigmentation, transverse leuconychia and transverse melanonychia after chemotherapy for Hodgkin's disease. Author(s): Lang K, Groeger M, Neumann NJ, Ruzicka T, Fritsch C. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 March; 16(2): 162-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046824

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Syndrome of polyneuropathy, skin hyperpigmentation, oedema and hepatosplenomegaly. Author(s): Tang LM, Hsi MS, Ryu SJ, Minauchi Y. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1983 December; 46(12): 1108-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6663309

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Synergism of minocycline and amitriptyline in cutaneous hyperpigmentation. Author(s): Basler RS, Goetz CS. Source: Journal of the American Academy of Dermatology. 1985 March; 12(3): 577. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3989016

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Systematized, unilateral, velvety hyperpigmentation and homolateral patches of curled hairs. Author(s): Revenga F, Ferrando J, Grimalt R, Sanz-Moncasi P, Lopez A, Paricio J. Source: Pediatric Dermatology. 2000 September-October; 17(5): 417-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11085677

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Systemic lupus erythematosus with acanthosis nigricans, hyperpigmentation, and insulin receptor antibody. Author(s): Baird JS, Johnson JL, Elliott-Mills D, Opas LM. Source: Lupus. 1997; 6(3): 275-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9104736

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Tegafur-induced acral hyperpigmentation. Author(s): Llistosella E, Codina A, Alvarez R, Pujol RM, de Moragas JM. Source: Cutis; Cutaneous Medicine for the Practitioner. 1991 September; 48(3): 205-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1935249

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The diagnostic dilemma of hyperpigmentation in patients with acquired immunodeficiency syndrome. Author(s): Tal A, Gagel RF. Source: Cutis; Cutaneous Medicine for the Practitioner. 1991 August; 48(2): 153-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1935242

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The epidermal stem cell factor is over-expressed in lentigo senilis: implication for the mechanism of hyperpigmentation. Author(s): Hattori H, Kawashima M, Ichikawa Y, Imokawa G. Source: The Journal of Investigative Dermatology. 2004 May; 122(5): 1256-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15140230

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The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen's disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor. Author(s): Okazaki M, Yoshimura K, Suzuki Y, Uchida G, Kitano Y, Harii K, Imokawa G. Source: The British Journal of Dermatology. 2003 April; 148(4): 689-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752125

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The mechanism of epidermal hyperpigmentation in dermatofibroma is associated with stem cell factor and hepatocyte growth factor expression. Author(s): Shishido E, Kadono S, Manaka I, Kawashima M, Imokawa G. Source: The Journal of Investigative Dermatology. 2001 September; 117(3): 627-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11564169

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The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1. Author(s): Manaka L, Kadono S, Kawashima M, Kobayashi T, Imokawa G. Source: The British Journal of Dermatology. 2001 December; 145(6): 895-903. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11899142

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The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis. Author(s): Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 1997 August; 10(4): 218-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263329

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The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis. Author(s): Kadono S, Manaka I, Kawashima M, Kobayashi T, Imokawa G. Source: The Journal of Investigative Dermatology. 2001 April; 116(4): 571-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11286625

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The significance of eccentric foci of hyperpigmentation ('small dark dots') within melanocytic nevi. Analysis of 59 cases. Author(s): Bolognia JL, Lin A, Shapiro PE. Source: Archives of Dermatology. 1994 August; 130(8): 1013-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8053697

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Thymic carcinoid with cutaneous hyperpigmentation. Author(s): Lieske TR, Kincaid J, Sunderrajan EV. Source: Archives of Internal Medicine. 1985 February; 145(2): 361-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3977500

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Transdermal clonidine: an association with recurrent herpes simplex and hyperpigmentation. Author(s): Wiser TH, Kazakis AM, LaCivita CL. Source: Journal of the American Academy of Dermatology. 1987 July; 17(1): 143-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3611448

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Transient hyperpigmentation after calcipotriol ointment and PUVA therapy in psoriatic patients. Author(s): Vazqvez-Lopez F, Perez-Oliva N. Source: Acta Dermato-Venereologica. 1996 September; 76(5): 400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8891019

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Treatment of atrophoderma of Pasini and Pierini-associated hyperpigmentation with the Q-switched alexandrite laser: a clinical, histologic, and ultrastructural appraisal. Author(s): Arpey CJ, Patel DS, Stone MS, Qiang-Shao J, Moore KC. Source: Lasers in Surgery and Medicine. 2000; 27(3): 206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11013382

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Treatment of gingival hyperpigmentation for esthetic purposes by Nd:YAG laser: report of 4 cases. Author(s): Atsawasuwan P, Greethong K, Nimmanon V. Source: J Periodontol. 2000 February; 71(2): 315-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10711623

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Treatment of minocycline-induced hyperpigmentation with the Q-switched ruby laser. Author(s): Tsao H, Busam K, Barnhill RL, Dover JS. Source: Archives of Dermatology. 1996 October; 132(10): 1250-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8859045

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Treatment of nonmelanotic hyperpigmentation with the Q-switched ruby laser. Author(s): Becker-Wegerich PM, Kuhn A, Malek L, Lehmann P, Megahed M, Ruzicka T. Source: Journal of the American Academy of Dermatology. 2000 August; 43(2 Pt 1): 2724. Erratum In: J Am Acad Dermatol 2000 October; 43(4): 609. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10906650

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Tretinoin for hyperpigmentation in black patients. Author(s): LaVoo EJ. Source: The New England Journal of Medicine. 1993 November 11; 329(20): 1503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8413468

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Ultrastructural and x-ray microanalytical observations of minocycline-related hyperpigmentation of the skin. Author(s): Sato S, Murphy GF, Bernhard JD, Mihm MC Jr, Fitzpatrick TB. Source: The Journal of Investigative Dermatology. 1981 September; 77(3): 264-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7264358

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Ultrastructural findings in oral hyperpigmentation of HIV-infected patients. Author(s): Zhang X, Langford A, Gelderblom H, Reichart P. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1989 September; 18(8): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2607467

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Ultraviolet light and hyperpigmentation in healing wounds. Author(s): Wiemer DR, Spira M. Source: Annals of Plastic Surgery. 1983 October; 11(4): 328-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6638839

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Unilateral linear hyperpigmentation of the skin with ipsilateral sectorial hyperpigmentation of the retina. Author(s): Meyer CH, Freyschmidt-Paul P, Happle R, Kroll P. Source: American Journal of Medical Genetics. 2004 April 1; 126A(1): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039978

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Unusual hyperpigmentation developing in congenital reticular ichthyosiform erythroderma (ichthyosis variegata). Author(s): Brusasco A, Cambiaghi S, Tadini G, Berti E, Caputo R. Source: The British Journal of Dermatology. 1998 November; 139(5): 893-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9892962

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Unusual serpentine hyperpigmentation associated with 5-fluorouracil. Case report and review of cutaneous manifestations associated with systemic 5-fluorouracil. Author(s): Vukelja SJ, Bonner MW, McCollough M, Cobb PW, Gaule DA, Fanucchi PJ, Keeling JH. Source: Journal of the American Academy of Dermatology. 1991 November; 25(5 Pt 2): 905-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1837033

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Unusual striped hyperpigmentation of the torso. A sequel of abnormalities of epitrichial exfoliation. Author(s): Gibbs RC. Source: Archives of Dermatology. 1967 April; 95(4): 385-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6067148

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Upper extremity swelling and hyperpigmentation due to onchocerciasis in an American. Author(s): Joyce MP, Pearson RD. Source: Southern Medical Journal. 1987 November; 80(11): 1452-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3686152

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Vaginal hyperpigmentation due to ochronosis. Author(s): Gatcliffe TA, Soto-Wright V, Kasznica J. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 2): 1066-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738104

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Verrucose areolar hyperpigmentation of pregnancy. Author(s): Garcia RL. Source: Archives of Dermatology. 1973 May; 107(5): 774. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4267295

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Vitamin B12 deficiency: a case report of ongoing cutaneous hyperpigmentation. Author(s): Hoffman CF, Palmer DM, Papadopoulos D. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 February; 71(2): 127-30; Quiz 138-40. Erratum In: Cutis. 2003 April; 71(4): 322. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635892

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Weisburg and Greenbaum describe several cases of postinflammatory hyperpigmentation. Author(s): Bargman H. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2004 January; 30(1): 122; Author Reply 122. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983879

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What is your diagnosis? Hyperpigmentation due to long-term chlorpromazine use. Author(s): Kass J, Hsu S. Source: Cutis; Cutaneous Medicine for the Practitioner. 2001 October; 68(4): 252, 260. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11710442

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Zebra-like hyperpigmentation in an infant with multiple congenital defects. Author(s): Alimurung FM, Lapenas D, Willis I, Lang P. Source: Archives of Dermatology. 1979 July; 115(7): 878-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=453903

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

Finding Nutrition Studies on Hyperpigmentation 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.4 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 “hyperpigmentation” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

4 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 “hyperpigmentation” (or a synonym): •

Generalized melanosis in metastatic malignant melanoma: the possible role of DOPAquinone metabolites. Author(s): Department of Dermatology, Yamanashi Medical University, Yamanashi, Japan. Source: Tsukamoto, K Furue, M Sato, Y Takayama, O Akasu, R Ohtake, N Wakamatsu, K Ito, S Tamaki, K Shimada, S Dermatology. 1998; 197(4): 338-42 1018-8665

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Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin. Author(s): Department of Dermatology, Kobe University School of Medicine, Japan. Source: Ando, H Ryu, A Hashimoto, A Oka, M Ichihashi, M Arch-Dermatol-Res. 1998 July; 290(7): 375-81 0340-3696

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

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

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

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

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

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

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

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

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

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

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

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

Nutrition

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

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

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

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

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

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

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

Food and Diet Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Shrimp Source: Healthnotes, Inc.; www.healthnotes.com

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

5,6-Dihydroxyindoles in the fenton reaction: a model study of the role of melanin precursors in oxidative stress and hyperpigmentary processes. Author(s): Novellino L, Napolitano A, Prota G. Source: Chemical Research in Toxicology. 1999 October; 12(10): 985-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10525276

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A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Author(s): Silva AJ, Frankland PW, Marowitz Z, Friedman E, Laszlo GS, Cioffi D, Jacks T, Bourtchuladze R, Lazlo G. Source: Nature Genetics. 1997 March; 15(3): 281-4. Erratum In: Nat Genet 2002 August; 31(4): 439. Lazlo G [corrected to Laszlo Gs]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9054942

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A new type of tyrosinase inhibitors from natural products as potential treatments for hyperpigmentation. Author(s): Badria FA, elGayyar MA. Source: Boll Chim Farm. 2001 July-August; 140(4): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570225

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A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian. Author(s): Higginbottom MC, Sweetman L, Nyhan WL. Source: The New England Journal of Medicine. 1978 August 17; 299(7): 317-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=683264

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A two-centre collaborative study on clinico-epidemiological profile of a recent outbreak of epidemic dropsy in New Delhi (India) with special emphasis on its cardiac manifestations in pediatric patients. Author(s): Aggarwal KC, Prasad MS, Salhan RN, Yadav D, Pandit N, Goyal PC, Garg M. Source: Journal of Tropical Pediatrics. 2001 October; 47(5): 291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11695729

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Acneiform eruptions after facial beauty treatment. Author(s): Khanna N, Gupta SD. Source: International Journal of Dermatology. 1999 March; 38(3): 196-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10208615

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Argyria following the use of dietary supplements containing colloidal silver protein. Author(s): Gulbranson SH, Hud JA, Hansen RC. Source: Cutis; Cutaneous Medicine for the Practitioner. 2000 November; 66(5): 373-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11107524

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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 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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Assessment of topical hypopigmenting agents on solar lentigines of Asian women. Author(s): Hermanns JF, Petit L, Pierard-Franchimont C, Paquet P, Pierard GE. Source: Dermatology (Basel, Switzerland). 2002; 204(4): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12077522

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Benzylamide derivative compound attenuates the ultraviolet B-induced hyperpigmentation in the brownish guinea pig skin. Author(s): Choi SY, Kim S, Hwang JS, Lee BG, Kim H, Kim SY. Source: Biochemical Pharmacology. 2004 February 15; 67(4): 707-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757170

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Berloque dermatitis induced by “Florida water”. Author(s): Wang L, Sterling B, Don P. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 July; 70(1): 29-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184670

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Bleomycin-induced hyperpigmentation and hypersensitivity reactions to etoposide and vinblastine in a child with endodermal sinus tumor. Author(s): Mutafoglu-Uysal K, Sarialioglu F, Olgun N. Source: Turk J Pediatr. 2001 April-June; 43(2): 172-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11432501

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Blue light inhibits melanin synthesis in B16 melanoma 4A5 cells and skin pigmentation induced by ultraviolet B in guinea-pigs. Author(s): Ohara M, Kobayashi M, Fujiwara H, Kitajima S, Mitsuoka C, Watanabe H. Source: Photodermatology, Photoimmunology & Photomedicine. 2004 April; 20(2): 8692. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030593

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Bullous phytophotodermatitis associated with high natural concentrations of furanocoumarins in limes. Author(s): Wagner AM, Wu JJ, Hansen RC, Nigg HN, Beiere RC. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 2002 March; 13(1): 10-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11887098

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Burkitt's lymphoma. Author(s): Wray EB. Source: W V Med J. 1975 January; 71(1): 8-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1053848

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Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary.

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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 •

Chronic hyperpigmentation from a heated mustard compress burn: a case report. Author(s): Linder SA, Mele JA 3rd, Harries T. Source: The Journal of Burn Care & Rehabilitation. 1996 July-August; 17(4): 351-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8844357

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Contact leukomelanosis induced by the leaves of Piper betle L. (Piperaceae): a clinical and histopathologic survey. Author(s): Liao YL, Chiang YC, Tsai TF, Lee RF, Chan YC, Hsiao CH. Source: Journal of the American Academy of Dermatology. 1999 April; 40(4): 583-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10188678

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Davener's dermatosis: a variant of friction hypermelanosis. Author(s): Naimer SA, Trattner A, Biton A, Avinoach I, Vardy D. Source: Journal of the American Academy of Dermatology. 2000 March; 42(3): 442-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10688714

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Hemorrhagic colitis and pseudomelanosis coli in ipecac ingestion by proxy. Author(s): Johnson JE, Carpenter BL, Benton J, Cross R, Eaton LA Jr, Rhoads JM. Source: Journal of Pediatric Gastroenterology and Nutrition. 1991 May; 12(4): 501-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678009

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Hyperpigmentation and contact dermatitis due to Juglans regia. Author(s): Bonamonte D, Foti C, Angelini G. Source: Contact Dermatitis. 2001 February; 44(2): 101-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11205381

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Hyperpigmentation and secondary hemochromatosis: a novel treatment with extracorporeal chelation. Author(s): Held JL, Yankiver B, Kohn SR. Source: Journal of the American Academy of Dermatology. 1993 February; 28(2 Pt 1): 253-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8432923

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Hyperpigmentation due to calcipotriol (MC 903) plus heliotherapy in psoriatic patients. Three case reports. Author(s): Kokelj F, Lavaroni G, Perkan V, Plozzer C. Source: Acta Dermato-Venereologica. 1995 July; 75(4): 307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8578956

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Ifosfamide-induced hyperpigmentation. Author(s): Yule SM, Pearson AD, Craft AW. Source: Cancer. 1994 January 1; 73(1): 240-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8275433

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Ifosfamide-induced hyperpigmentation. Author(s): Teresi ME, Murry DJ, Cornelius AS. Source: Cancer. 1993 May 1; 71(9): 2873-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8385568

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Images in clinical medicine. Melanosis coli. Author(s): Ahmed S, Gunaratnam NT. Source: The New England Journal of Medicine. 2003 October 2; 349(14): 1349. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523143

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Initial description of gastric melanosis in a laxative-abusing patient. Author(s): Mitty RD, Wolfe GR, Cosman M. Source: The American Journal of Gastroenterology. 1997 April; 92(4): 707-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9128333

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Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin. Author(s): Ando H, Ryu A, Hashimoto A, Oka M, Ichihashi M. Source: Archives of Dermatological Research. 1998 July; 290(7): 375-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9749992

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Melanosis coli associated with ingestion of bamboo leaf extract. Author(s): Iseki K, Ishikawa H, Suzuki T, Murakami T, Otani T, Ishiguro S. Source: Gastrointestinal Endoscopy. 1998 March; 47(3): 305-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9540889

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Melanosis coli involving pericolonic lymph nodes associated with the herbal laxative Swiss Kriss: a rare and incidental finding in a patient with colonic adenocarcinoma. Author(s): Ewing CA, Kalan M, Chucker F, Ozdemirli M.

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Source: Archives of Pathology & Laboratory Medicine. 2004 May; 128(5): 565-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086301 •

Melanosis coli with liver involvement. Author(s): Dubilier LD, Burkhart RC. Source: J Ky Med Assoc. 1975 March; 73(3): 143-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1127310

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Melanosis coli: a consequence of “alternative therapy” for psoriasis. Author(s): Bertram PD. Source: The American Journal of Gastroenterology. 1993 June; 88(6): 971. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8503405

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Oral melanin pigmentation in 467 Thai and Malaysian people with special emphasis on smoker's melanosis. Author(s): Hedin CA, Axell T. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1991 January; 20(1): 8-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2002444

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Regional dermatoses in the African. Part I. Facial hypermelanosis. Author(s): Olumide YM, Odunowo BD, Odiase AO. Source: International Journal of Dermatology. 1991 March; 30(3): 186-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1828060

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Supravenous hyperpigmentation in association with CHOP chemotherapy of a CD30 (Ki-1)-positive anaplastic large-cell lymphoma. Author(s): Schulte-Huermann P, Zumdick M, Ruzicka T. Source: Dermatology (Basel, Switzerland). 1995; 191(1): 65-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8589490

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Supravenous hyperpigmentation induced by vinorelbine. Author(s): Cecchi R, Tuci F, Giomi A, Innocenti F. Source: Dermatology (Basel, Switzerland). 1994; 188(3): 244. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8186521

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The pigment of melanosis coli: a lectin histochemical study. Author(s): Benavides SH, Morgante PE, Monserrat AJ, Zarate J, Porta EA. Source: Gastrointestinal Endoscopy. 1997 August; 46(2): 131-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9283862

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Treatment of Ota's nevus and melanosis by xuejiebiandou (resina draconis, semen dolichoris album) decoction. Author(s): Xu HQ, Liang CR, Feng J, Liu FR. Source: J Tradit Chin Med. 1982 December; 2(4): 289-92. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6765725

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Unraveling the patterns of subclinical pheomelanin-enriched facial hyperpigmentation: effect of depigmenting agents. Author(s): Hermanns JF, Petit L, Martalo O, Pierard-Franchimont C, Cauwenbergh G, Pierard GE. Source: Dermatology (Basel, Switzerland). 2000; 201(2): 118-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11053913

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to hyperpigmentation; 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 Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com

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Sunburn Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements ALA Source: Integrative Medicine Communications; www.drkoop.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the 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. PATENTS ON HYPERPIGMENTATION 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.5 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 “hyperpigmentation” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hyperpigmentation, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Hyperpigmentation By performing a patent search focusing on hyperpigmentation, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 5Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on hyperpigmentation: •

Compositions and systems for the treatment of hyperpigmentation Inventor(s): Gans; Eugene (Phoenix, AZ), Gordon; Benjamin D. (Yarmouth Port, MA) Assignee(s): Medicis Pharmaceutical Corp. (Phoenix, AZ) Patent Number: 5,932,612 Date filed: August 5, 1997 Abstract: A novel skin lightening preparation and its method of use are described. The composition and method are characterized by reduced skin irritation, while providing skin lightening that is at least as effective as known over-the-counter preparations. Excerpt(s): This invention relates to pigmentation disorders, specifically hyperpigmentation. Melanin, a pigment found in human skin, is produced by cells known as melanocytes. Melanocytes produce melanin in granules called melanosomes. Melanosomes are transferred from the melanocytes to keratinocytes, a layer of keratinproducing cells that is closer to the outer surface of the skin. The more melanosomes that are transferred to the keratinocytes, the darker the skin appears. This process can be altered in persons of any skin type or race. Alteration that results in excessive darkening is known as hyperpigmentation. Hyperpigmentation can take a variety of forms. Melasma is a form of hyperpigmentation in pregnant women that is characterized by dark patches on the cheeks and forehead, and is sometimes called "pregnancy mask". With age, many persons develop dark spots sometimes known as "liver spots." Hyperpigmentation is sometimes a side effect of birth control pills, and can be a persistent result of acne, bums, bites and other skin injuries. Web site: http://www.delphion.com/details?pn=US05932612__

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Compositions for treatment of hyperpigmentation and methods for making and using such compositions Inventor(s): Clark; Kathleen L. (Medusa, NY), Popp; Karl F. (Schodack Landing, NY) Assignee(s): Stiefel Laboratories, Inc. (Coral Gables, FL) Patent Number: 6,699,464 Date filed: July 30, 2002 Abstract: A composition for treatment of hyperpigmentation having a SPF value of at least 15 includes hydroquinone, sunscreens, antioxidants and emulsifiers and emollients. The composition can be made into an emulsion having physical and chemical stability for a prolonged period of time over a wide range of temperatures. Excerpt(s): This invention relates to treating hyperpigmentation. In particular, it relates to compositions for treating hyperpigmentation of human skin which can offer protection from UVA and/or UVB radiation and further relates to methods for making and using such compositions. Aging, birth control pills, pregnancy, and certain types of skin injuries can cause dark areas on the skin. This condition is usually referred to as hyperpigmentation. Certain compounds have been found to reduce or eliminate hyperpigmentation when they are introduced into the affected skin areas. One approach to treating hyperpigmentation is by placing a compound which reduces

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hyperpigmentation on the skin. Generally, the compound which reduces hyperpigmentation is incorporated into a cream which is placed on the skin. It is desirable to have a hyperpigmentation-treating compound that is incorporated in a cream which soaks into the skin without leaving a residue. Such creams are often referred to as vanishing creams. The only FDA-approved product for treatment of hyperpigmentation is hydroquinone. Hydroquinone has been found effective in reducing hyperpigmentation when applied to the affected skin areas. Hydroquinone, however, causes skin irritation. Accordingly, hydroquinone must be applied with ingredients which reduce or eliminate skin irritation of hydroquinone. Topical formulations of hydroquinone for treating hyperpigmentation have been marketed in the United States under the names Eldoquin.RTM., Eldopaque-Forte.RTM., Eldoquin.RTM. Forte, and Glyquin.RTM. Hydroquinone products lighten the color of the skin areas to which it is applied by killing off the melanin making cells--the melanocytes. Web site: http://www.delphion.com/details?pn=US06699464__ •

Method of treating post-inflammatory hyperpigmentation in black skin with a retinoid, and method of lightening black skin with a retinoid Inventor(s): Ellis; Charles N. (Ann Arbor, MI), Griffiths; Christopher E. M. (Manchester, GB), Voorhees; John J. (Ann Arbor, MI) Assignee(s): Regents of the University of Michigan (Ann Arbor, MI) Patent Number: 6,017,960 Date filed: May 12, 1998 Abstract: Treatment of post-inflammatory hyperpigmentation (PIH) in black and asian skin is accelerated from natural healing by use of a composition comprising a retinoid and/or an inhibitor of cytochrome P-450 enzyme-mediated degradation of retinoids, the composition does not require a conventional depigmenting or bleaching agent (such as a hydroquinone) as is typically used. Healing of PIH lesions is accelerated about three to five times from normal healing. Additionally, these compositions are useful separately for lightening black or asian skin. Excerpt(s): The present method relates to a method of treating hyperpigmentation in black skin with retinoic acid and a method of lightening black skin with retinoic acid. In recent studies on the use of topically applied retinoic acid (RA) for the treatment of photodamaged skin, lightening of sun-induced dyspigmentation, i.e., actinic lentigines, has been observed (J. S. Weiss et al., JAMA, 259:527-32 (1988); A. M. Kligman et al., J. Am. Acad. Dermatol., 15:836-59 (1986); G. D. Weinstein et al., Arch. Denmatol., 127:65965 (1991); E. S. Rafal et al., New Engl. J. Med., 326:368-374 (1992); C. N. Ellis et al., J. Am. Acad. Dennatol., 23:629-37 (1990); and E. A. Olsen et al., J. Am. A cad. Dermatol., 26:21524 (1992)). Sun-induced dyspigmentation is a heterogeneous entity in whites (E. S. Rafal et al., New Engl. J. Med., 326:368-374 (1992)) which may share features of melanin deposition with PIH. RA has not been used previously for PIH because it was thought to cause, rather than ameliorate, hyperpigmentation, and to be poorly tolerated (C. J. McDonald et al., Prog. in Dermatol., 4:15-20 (1992)). Topical RA treatment has also been reported as effective for the treatment of liver spots associated with photodamage (E. S. Rafal et al., New Engl. J. Med., 326:368-74 (1992)). A need remains in the art for a method of treating post-inflammatory hyperpigmentation. In addition, a method of lightening black skin would also be desirable.

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Web site: http://www.delphion.com/details?pn=US06017960__ •

Method of treatment of hyperpigmentation in black skin with retinoic acid and method of lightening black skin with retinoic acid Inventor(s): Ellis; Charles N. (Ann Harbor, MI), Griffiths; Christopher E. M. (Ann Harbor, MI), Voorhees; John J. (Ann Harbor, MI) Assignee(s): The Regents of the University of Michigan (Ann Arbor, MI) Patent Number: 5,750,570 Date filed: March 31, 1992 Abstract: Hyperpigmentation of black skin may be treated by topical application of retinoic acid to the skin. Topical application of retinoic acid is also effective for lightening normal black skin. Excerpt(s): The present method relates to a method of treating hyperpigmentation in black skin with retinoic acid and a method of lightening black skin with retinoic acid. In recent studies of topical retinoic acid (RA) treatment of photodamage, lightening of suninduced dyspigmentation, i.e., actinic lentigines, has been observed (Weiss J. S. et al, JAMA, 1988, 259:527-32; Kligman A. M. et al, J. Am. Acad. Dermatol., 1986; 15:836-59; Weinstein G. D. et al, Arch. Dermatol., 1991; 127:659-65; Rafal E. S. et al, New Engl. J. Med., 1992; 326:368-374; Ellis C. N. et al, J. Am. Acad. Dermatol., 1990; 23:629-37; and Olsen E. A. et al, J. Am. Acad. Dermatol., 1992; 26:215-24). Sun-induced dyspigmentation is a heterogeneous entity in whites (Rafal E. S. et al, New Engl. J. Med., 1992, 326:368-374) which may share features of melanin deposition with PIH. RA has not been previously used for PIH, because it is thought to cause hyperpigmentation and to be poorly tolerated (McDonald C. J. et al, Progress in Dermatology, 1973; 4:15-20). Topical RA treatment has also been reported as effective for the treatement of liver spots associated with photodamage (Rafal E. S. et al, New Engl. J. Med., 1992; 326:368-74). Thus, there remains a need for a method for treating hyperpigmentation. In addition, a method of lightening black skin would also be desirable. Web site: http://www.delphion.com/details?pn=US05750570__

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Methods of identifying hyperpigmentation

ocular

hypotensive

compounds

having

reduced

Inventor(s): Krauss; Achim H-P (Foothill Ranch, CA), Mac Neil; Sheila (Sheffield, GB), Shi; Licheng (Irvine, CA), Smith-Thomas; Linda C. (Sheffield, GB), Spada; Clayton S. (Fullerton, CA), Woodward; David F. (Lake Forest, CA) Assignee(s): Allergan, Inc. (Irvine, CA) Patent Number: 6,713,268 Date filed: June 26, 2001 Abstract: Methods to identify agents having ocular hypotensive activity which have reduced or absent ability to stimulate iridial hyperpigmentation are disclosed. The methods reside in part in detecting the ability of a test compound to interact with the FP receptor. Excerpt(s): The invention relates primarily to the treatment of ocular hypertension, such as that associated with glaucoma, with agents comprising prostaglandin analogs or

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derivatives wherein treatment with the agent results in minimal or absent ocular hyperpigmentation effects. Additionally, the invention concerns methods to identify and design prostaglandin F analogs which lack the ability to effect hyperpigmentation. Certain prostaglandins and their analogs and derivatives, such as the PGF.sub.2.alpha., derivative latanoprost, sold under the trademark XALATAN.RTM., have been established as compounds useful in treating ocular hypertension and glaucoma. However, latanoprost, the first prostaglandin approved by the United States Food And Drug Administration for this indication, is a prostaglandin derivative possessing the undesirable side effect of producing an increase in brown pigment in the iris of 5-15% of human eyes. The change in color results from an increased number of melanosomes (pigment granules) within iridial melanocytes. See e.g., Watson et al., Ophthalmology 103:126 (1996) (this and all references cited herein are incorporated by reference). While it is still unclear whether this effect has additional and deleterious clinical ramifications, from a cosmetic standpoint alone such side effects are undesirable. It would be desirable to devise methods of treating a patient having glaucoma with a prostaglandin, prostaglandin analog or prostaglandin derivative that either lacks or has a reduced ability to stimulate an increase in iridial pigmentation as compared to a synthetic ocular hypertensive prostaglandin derivative, such as latanoprost. By prostaglandin derivative is meant a compound having structural similarity to a prostaglandin, preferably a PGF prostaglandin, having carboxylic acid groups, and esters thereof. Web site: http://www.delphion.com/details?pn=US06713268__ •

Pharmaceutical and cosmetic depigmentation compositions with a caffeic acid base Inventor(s): Candau; Didier (Melun, FR), Charpin; Isabelle (St Maur Des Fosses, FR), Millecamps; Francois (Paris, FR), Montastier; Christiane (Maisons Laffitte, FR), N'Guyen; Quang L. (Antony, FR) Assignee(s): L'Oreal (Paris, FR) Patent Number: 5,164,185 Date filed: August 13, 1991 Abstract: A pharmaceutical or cosmetic depigmenting composition for application to the skin so as to improve the aesthetic appearance of the skin or to treat pathological or accidental hyperpigmentation contains caffeic acid or an ester or amide thereof in an amount effective to depigment the skin. Excerpt(s): The present invention relates to a pharmaceutical or cosmetic depigmenting composition which contains, as an active ingredient, caffeic acid or one of its derivatives. tyrosinase being the main enzyme involved in this series of reactions. The depigmenting agents currently used in cosmetology are, more specifically, phenolic derivatives, and, most notably, hydroquinone or a hydroquinone ether such as hydroquinone monomethyl ether. Web site: http://www.delphion.com/details?pn=US05164185__

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Process for treatment of hyperpigmentary dermatoses Inventor(s): Nazzaro-Porro; Marcella (Via Viminale 38, Rome, IT) Assignee(s): none reported Patent Number: 4,292,326 Date filed: December 1, 1978 Abstract: There is disclosed a composition for the treatment of acne, hyperpigmentary dermatoses or skin hyperpigmentation which contains dicarboxylic acids containing 7 to 13 carbon atoms or certain derivatives thereof that contain reducing functional group or a salt thereof. There are also disclosed methods for preparing mercapto derivatives of these dicarboxylic acids. Excerpt(s): This invention relates to compositions for the treatment of acne, hyperpigmentary dermatoses and the like. Acne is a widespread skin ailment which comprises an abnormal condition affecting chiefly the skin of the face (but also that of the shoulders and chest), characterized by the development of pimples, blackheads, and pustules, and caused by an infection and inflammation of the wax-producing (sebaceous) glands. The most common form is known as acne vularis and occurs cheifly in young people between the ages of 12 or 13 and 20. It is believed that the initiating cause of acne is a temporary abnormality in the activity of certain glands, especially the sex glands (which in the early teen years become highly functional and sometimes unstable) and the glands concerned with growth. Emotional upheavals, which upset the glandular balance and normal function, also result in an outbreak of acne. Dermatoses, such as skin hyperpigmentations (which frequently produce a disfiguring effect, such as in the case of chloasma of the face), constitute a problem not only of an esthetic but also of a therapeutic nature, for which as yet no basic solution has been found. Only hydroquinone and its derivatives have up to now shown some effectiveness, in vivo, for the treatment of skin hyperpigmentations. However, they cause as a side effect, the development of long-lasting hypopigmented zones, which are at times irreducible. An object of the present invention is to provide compositions which are useful for normalizing the color of skin effected by non-cancerous or non-precancerous hyperpigmentation. Web site: http://www.delphion.com/details?pn=US04292326__

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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

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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 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__ •

Topical use of 3-phenylacetylamino-2,6-piperidinedione for treatment of skin wrinkles and hyperpigmentation Inventor(s): Burzynski; Stanislaw R. (#5 Concord Cir., Houston, TX 77024) Assignee(s): none reported Patent Number: 4,593,038 Date filed: April 3, 1985 Abstract: A cosmetic composition is provided which comprises 3-phenylacetylamino2,6-piperidinedione dispersed in a cosmetically suitable vehicle. This cosmetic composition is useful in the topical cosmetic treatment of skin areas affected with wrinkles or hyperpigmentation. Excerpt(s): The present invention relates generally to cosmetic compositions and their use in reducing wrinkles and spots of hyperpigmentation of the skin. More particularly, the compositions comprise an amino acid derivative, 3-phenylacetylamino-2,6piperidinedione, in a cosmetically acceptable vehicle. Wrinkles are usually a natural consequence of aging. By age twenty-five, a person usually observes some facial wrinkles which accompany cutaneous age-related changes. These changes include loss of subdermal fat, a diminution of muscle tone, and a loss of elasticity. These changes parallel a decrease in collagen and elastin fiber content. Hormonal changes also occur and are linked to a decrease in the water-binding capacity of the skin tissue. In addition to aging, wind, sunlight and disease are among other contributing causes of skin wrinkles. Either singly, on in combination, these forces promote inelasticity and drying of skin tissues. Hyperpigmentation is generally related to dense melanin concentrations in skin tissues. The color of skin is determined by the amount and size of melanin accumulation. Hyperpigmentation of the skin occurs when there is an increased production of melanin. Spots of hyperpigmentation may result from natural phenomena or they may be caused by external stress, drugs, or other dysfunctions. Most common types of localized hyperpigmentation includes: lentigo, ephelis (freckles), nevus and melasma. The last type corresponds to hyperpigmentation in pregnant

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women or women taking oral contraceptives and is due to increased level of melanocyte-stimulating hormone and adrenocorticotrophic hormone produced by the pituitary gland. Web site: http://www.delphion.com/details?pn=US04593038__ •

Treatment of skin diseases and tumors with esters and amides of monocarboxylic acids Inventor(s): Thornfeldt; Carl R. (Ontario, OR) Assignee(s): Cellegy Pharmaceuticals, Inc. (Novato, CA) Patent Number: 5,231,087 Date filed: January 22, 1992 Abstract: Noninfectious inflammatory and hyperpigmentation skin diseases, thermal injuries and premalignant skin tumors induced by radiation or virus, in both humans and animals, are treated with topical formulations of an ester or amide of a monocarboxylic acid, the acid moiety of which is 9 to 18 carbon atoms. Excerpt(s): Certain classes of noninfections inflammatory and hyperpigmentation diseases of the skin, thermal injuries of the skin, and premalignant skin tumors induced by ultraviolet or x-ray radiation or viruses, particularly those diseases which are multifactorial with a genetic predisposition, have yet to find a therapy which is fully satisfying. The standard therapies generally consist of the administration of antimicrobial agents which, depending on the disease, result in varying degrees of clearing of the disease condition. None of them however completely clear the disease. Prominent among these diseases are the ichthyoses, rosacea, acne vulgaris, psoriasis, various types of dermatitis, melasma and actinic lentigos, actinic keratoses, Bowenoid papulosus, condylomatous dysplasia, cervical carcinoma, Bowen's disease and lentigo maligna. Rosacea is an inflammatory disease due to abnormal sensitivity of the vasculature. Rosacea often results in secondary sebaceous gland hyperplasia and inflammation producing characteristic skin lesions. Treatments for rosacea generally involve the administration of antiinflammatory antibiotics such as Metronidizole. Web site: http://www.delphion.com/details?pn=US05231087__

Patent Applications on Hyperpigmentation As of December 2000, U.S. patent applications are open to public viewing.6 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 hyperpigmentation:

6

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

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•

Compositions and methods for treating hyperpigmentation Inventor(s): Kyrou, Christos D.; (Suffern, NY), Mahalingam, Harish; (Westwood, NJ), Ptchelintsev, Dmitri; (Jersey City, NJ) Correspondence: Charles N.J. Ruggiero; Ohlandt, Greeley, Ruggiero & Perle, L.L.P.; 9th Floor; One Landmark Square,; Stamford; CT; 06901-2682; US Patent Application Number: 20020141953 Date filed: December 20, 2000 Abstract: There is provided a topical composition for treating, preventing or ameliorating hyperpigmentation in human skin. The composition has a de-pigmenting agent in an amount effect to reduce or diminish pigmentation at an area of skin to which it is applied, and a cosmetically or pharmaceutically acceptable vehicle. Suitable depigmenting agents include 3,3'-thiodipropionic acid, thiazolidine-2-carboxylic acid, kaempferol-7-glucoside, perilla oil, and clofibrate and clofibrate analogs and derivatives. There is also provided methods for treating, preventing or ameliorating hyperpigmentation in human skin. Excerpt(s): The present invention relates to compositions useful in treating hyperpigmentation of human skin. Further, the present invention relates to methods of applying the compositions to the skin to effect treatment. Human skin color is determined primarily by the content of the pigment melanin in the basal epidermis layer. Melanin is synthesized by the process of melanogenesis within melanocytes (pigment-producing cells). Melanin is deposited onto melanosomes, which are transferred to keratinocytes in the basal epidermal layer. Melanosomes present in these basal keratinocytes are the key determinants of skin color. The keratinocytes leave the basal layer and undergo differentiation forming the cornified top layer of the skin. Once the keratinocytes leave the basal layer, the melanosomes lose their characteristic electron dense structure, and the load of melanin is carried to the surface of the skin by the differentiating keratinocytes. The skin can become hyperpigmented when too much melanin concentrates at one area or portion of the skin due to the retention time of the melanosomes in the basal layer. Hyperpigmentation can also occur as a result of overexposure to the sun or other inflammatory stimuli. Hyperpigmentation can take the form of solar lentigines (age spots), ephilides (freckles), melasma, chloasma, and pigmented keratoses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Compositions that prevent post-traumatic hyperpigmentation and methods related thereto Inventor(s): Mann, Morris; (Glendale, AZ) Correspondence: The Halvorson Law Firm; 405 W. Southern AVE., Ste 1; Tempe; AZ; 85282; US Patent Application Number: 20030207932 Date filed: May 1, 2003 Abstract: The ingestion or topical administration of substances that inhibit leukotrienes prior to a trauma to the skin and for a period of time thereafter effectively inhibits the development of hyperpigmentation in people so predisposed.

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Excerpt(s): This application is a continuation of pending provisional application serial No. 60/377,857 filed on May 3, 2002. The present invention generally relates to substances that inhibit the effects of leukotrienes and more specifically prevent the development of hyperpigmentation after a traumatic event to affected skin. It is well known that people with certain skin types, i.e., people of Hispanic descent, African descent, Asian descent, and the like, are predisposed to hyperpigementation after a traumatic event to their skin. Such trauma can take the form of bums, abrasions, cuts, surgery, and the like. If the event is predetermined, it can be an additional trauma to the so predisposed individuals. This is particularly true for surgical procedures, laser phototherapy, dermabrasion, and other cosmetic procedures that may traumatize the skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cosmetic compositions and methods for using same to improve the aesthetic appearance of skin Inventor(s): Kyrou, Christos D.; (Goshen, NY), Mahalingam, Harish; (Ledgewood, NJ), Ptchelintsev, Dmitri; (Jersey City, NJ), Traudt, Michael; (Brookfield, CT) Correspondence: Rupa Sen; Avon Products, INC.; Avon Place; Suffern; NY; 10901; US Patent Application Number: 20040067245 Date filed: May 12, 2003 Abstract: The present invention relates to compositions useful in treating hyperpigmentation and the various signs of dermatological aging in human skin. The present invention also relates to cosmetic compositions and methods of using such compositions that improve the aesthetic appearance of skin. Further, the present invention relates to methods of applying the compositions to the skin to effect treatment and to improve the aesthetic appearance of skin, particularly, by providing anti-aging benefits to the skin.These and other objects of the present invention are achieved by a method and composition that comprises (a) a de-pigmenting agent or anti-aging agent in an amount effective to prevent, treat and/or ameliorate pigmentation or the various signs of aging at an area of skin to which it is applied, and (b) a cosmetically or pharmaceutically acceptable vehicle. Suitable de-pigmenting agents include 3,3'thiodipropionic acid, thiazolidine-2-carboxylic acid, Kaempferol-7-glucoside, perilla oil, and clofibrate and clofibrate analogs and/or derivatives, as well as those set forth below. Suitable anti-aging agents include 3,3'-thiodipropionic acid and/or its derivatives. Excerpt(s): This is a continuation-in-part application that claims priority to, and the benefit of, co-pending U.S. Ser. No. 09/741,383, filed Dec. 20, 2000, currently allowed and incorporated herein by reference. Human skin color is determined primarily by the content of the pigment melanin in the basal epidermis layer. Melanin is synthesized by the process of melanogenesis within melanocytes (pigment-producing cells). Melanin is deposited onto melanosomes, which are transferred to keratinocytes in the basal epidermal layer. Melanosomes present in these basal keratinocytes are the key determinants of skin color. The keratinocytes leave the basal layer and undergo differentiation forming the cornified top layer of the skin. Once the keratinocytes leave the basal layer, the melanosomes lose their characteristic electron dense structure, and the load of melanin is carried to the surface of the skin by the differentiating keratinocytes.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Glaucoma treatments with reduced hyperpigmentation Inventor(s): Krauss, Achim H-P; (Foothill Ranch, CA), Mac Neil, Sheila; (Sheffield, GB), Shi, Licheng; (Irvine, CA), Smith-Thomas, Linda C.; (Sheffield, GB), Spada, Clayton S.; (Fullerton, CA), Woodward, David F.; (Lake Forest, CA) Correspondence: Carlos A. Fisher; Allergan, INC.; T2-7h; 2525 Dupont Drive; Irvine; CA; 92612; US Patent Application Number: 20030018078 Date filed: June 26, 2001 Abstract: Methods to identify agents having ocular hypotensive activity which have reduced or absent ability to stimulate iridial hyperpigmentation are disclosed. The methods reside in part in detecting the ability of a test compound to interact with the FP receptor. Excerpt(s): The invention relates primarily to the treatment of ocular hypertension, such as that associated with glaucoma, with agents comprising prostaglandin analogs or derivatives wherein treatment with the agent results in minimal or absent ocular hyperpigmentation effects. Additionally, the invention concerns methods to identify and design prostaglandin F analogs which lack the ability to effect hyperpigmentation. Certain prostaglandins and their analogs and derivatives, such as the PGF.sub.2.alpha., derivative latanoprost, sold under the trademark Xalatan.RTM., have been established as compounds useful in treating ocular hypertension and glaucoma. However, latanoprost, the first prostaglandin approved by the United States Food And Drug Administration for this indication, is a prostaglandin derivative possessing the undesirable side effect of producing an increase in brown pigment in the iris of 5-15% of human eyes. The change in color results from an increased number of melanosomes (pigment granules) within iridial melanocytes. See e.g., Watson et al., Ophthalmology 103:126 (1996) (this and all references cited herein are incorporated by reference). While it is still unclear whether this effect has additional and deleterious clinical ramifications, from a cosmetic standpoint alone such side effects are undesirable. It would be desirable to devise methods of treating a patient having glaucoma with a prostaglandin, prostaglandin analog or prostaglandin derivative that either lacks or has a reduced ability to stimulate an increase in iridial pigmentation as compared to a synthetic ocular hypertensive prostaglandin derivative, such as latanoprost. By prostaglandin derivative is meant a compound having structural similarity to a prostaglandin, preferably a PGF prostaglandin, having carboxylic acid groups, and esters thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for regulating the condition of mammalian keratinous tissue via topical application of phytosterol compositions Inventor(s): Bissett, Donald Lynn; (Hamilton, OH), Oblong, John Erich; (Loveland, OH), Zhuang, John Chengfeng; (Cincinnati, OH) Correspondence: The Procter & Gamble Company; Patent Division; Sharon Woods Techinical Center; 11511 Reed Hartman Highway; Cincinnati; OH; 45241; US Patent Application Number: 20020098218 Date filed: November 26, 2001 Abstract: The present invention relates to methods for regulating the condition of mammalian keratinous tissue wherein the methods comprise the step of topically applying to the keratinous tissue of a mammal needing such treatment, a safe and effective amount of a composition comprising:a) a safe and effective amount of one or more phytosterols selected from the group consisting of.beta.-sitosterol, campesterol, brassicasterol,.DELTA.5-avennasterol, lupenol,.alpha.-spinasterol, stigmasterol, their derivatives, and combinations thereof; andb) a dermatologically acceptable carrier for the phytosterol.In additional embodiments, the above composition is suitable for thickening skin and preventing, retarding, and/or treating atrophy of mammalian skin, preventing, retarding, and/or treating the appearance of dark, under-eye circles and/or puffy eyes, preventing, retarding, and/or treating sallowness of mammalian skin, preventing and/or retarding tanning of mammalian skin, regulating and/or reducing the size of pores in mammalian skin, desquamating, exfoliating, and/or increasing turnover of mammalian skin, regulating oily/shiny appearance, preventing/retarding post-inflammatory hyperpigmentation in mammalian skin, and preventing and/or treating the appearance of cellulite in mammalian skin. Excerpt(s): This application is a divisional of U.S. application Ser. No. 09/439,438, filed Nov. 15, 1999, which claims priority under Title 35, United States Code 119(e) from Provisional Application No. 60/134,397, filed May 17, 1999. The present invention relates to methods of regulating the condition of mammalian keratinous tissue using defined phytosterols wherein the methods include: a) thickening skin and preventing, retarding, and/or treating atrophy in mammalian skin, b) preventing, retarding, and/or treating the appearance of dark, under-eye circles and puffy eyes, c) preventing, retarding, and/or treating sallowness of mammalian skin, d) preventing and/or retarding tanning of mammalian skin, e) desquamating, exfoliating, and/or increasing turnover of mammalian skin, f) regulating and/or reducing the size of pores in mammalian skin, g) regulating the oily and/or shiny appearance of mammalian skin, h) preventing, retarding, and/or treating post-inflammatory hyperpigmentation, and i) preventing and/or treating the appearance of cellulite in mammalian skin. These methods are accomplished via the topical application of compositions containing specific phytosterols to the skin of a mammal needing such treatments. Currently, there are a number of personal care products that are available to consumers, which are directed toward improving the health and physical appearance of keratinous tissues such as the skin, hair, and nails. The majority of these products are directed to delaying, minimizing or even eliminating skin wrinkling and other histological changes typically associated with the aging of skin or environmental damage to human skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for the treatment of hyperpigmentation of skin Inventor(s): Carmichael, Robin; (Redmond, WA), Patt, Leonard M.; (Seattle, WA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20030134781 Date filed: October 4, 2002 Abstract: Methods for treating hyperpigmentation of skin employ topical application of compositions to skin in need thereof, where the compositions comprise at least one peptide copper complex, or at least one peptide copper complex in combination with retinol, at least one retinol derivative, or a mixture thereof. Also disclosed are methods that use such compositions further comprising active agents selected from active drug substances, emollients, sunscreen agents, skin-lightening agents, skin protectants, skin conditioning agents, and humectants. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/364,657 filed Mar. 14, 2002 and U.S. Provisional Patent Application No. 60/327,640 filed Oct. 5, 2001, where the two provisional applications are incorporated herein by reference in their entireties. The present invention generally relates to the treatment of dermatological conditions, more specifically, of those conditions related to hyperpigmentation, by means of the topical application of compositions, effective therefor. Melanin is a dark pigment found in the skin of humans that is responsible for the darkening of the skin. Melanin is produced by specialized cells in the skin called malanocytes through a complicated series of chemical and enzymatic reactions, mainly involving the copper containing enzyme tyrosinase. The melanin pigments are packaged in granules called melanosomes. Melanosomes are transferred to the outer layer of the skin where they are responsible for the darkening of the skin, the degree of darkening being associated with skin type, sun exposure, and/or certain dermatological conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Peptide and its use in the treatment of hyperpigmentation conditions Inventor(s): Schallreuter, Karin U.; (Bradford, GB), Thody, Anthony J.; (Shipley, GB), Wood, John M.; (Bradford, GB) Correspondence: Eric S. Spector; Jones, Tullar & Cooper, P.C.; P.O. Box 2266; Eads Station; Arlington; VA; 22202; US Patent Application Number: 20030166570 Date filed: February 7, 2001 Abstract: A peptide having the formula:X--N(H)-A.sup.1-B.sup.2-C.sup.3-D.sup.4Lys.sup.5-Lys.sup.6-Arg.sup.7-C(O)- --YwhereinA, B, C and D are amino acid residues;X is selected from the group consisting of H, a pharmaceutically acceptable amine blocking group and, together with Y, a covalent bond connecting the carbonyl group of Arg.sup.7 to the amine group of A.sup.1; andY is selected from the group consisting of OH, a pharmaceutically acceptable carboxyl blocking group and, together with X, a covalent bond connecting the carbonyl group of Arg.sup.7 to the amine group of A.sup.1. Such peptides may be used topically to treat hyperpigmentation conditions such as melanism and melasma.

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Excerpt(s): The present invention relates to a peptide, a composition comprising a peptide and a method of treatment or prophylaxis of hyperpigmentation conditions using a composition comprising a peptide. Hyperpigmentation is a generic term for conditions in which an abnormal build up of pigment such as melanin results in darkening of body tissue, particularly the skin. Both melanosis and melasma are examples of hyperpigmentation conditions. Hyperpigmentation, particularly in regions of the skin that are usually exposed, for example around the face and hands, can be distressing for the sufferer and may result in a lack of self-confidence and even depression. Melanin is a black or dark brown pigment formed from the amino acid tyrosine in body cells known as melanocytes found in the epidermis. The production of melanin ("melanogenesis") is regulated by the interaction of.alpha.-melanocyte stimulating hormone (".alpha.-MSH"), derived from the precursor protein proopiomelanocortin ("POMC"), with the cAMP-coupled melanocortin-1 ("MC-1") receptors found on melanocytes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Topical pharmaceutical composition to treat hyperpigmentation of the skin Inventor(s): Hsu, Tsung-Min; (San Diego, CA), Luo, Eric C.; (Plano, TX), Maibach, Howard I.; (San Francisco, CA) Correspondence: Reed & Eberle Llp; 800 Menlo Avenue, Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20030072724 Date filed: June 21, 2002 Abstract: Provided is a topical pharmaceutical composition for skin lightening, which is particularly useful in treating skin hyperpigmentation, together with methods for its use. The composition and methods involve the topical use of an active agent effective in the treatment of skin hyperpigmentation plus a permeation-enhancing base that, in one embodiment, gives the composition a pH of about 8.0 to about 13.0, preferably about 8.0 to 11.5, and most preferably about 8.5 to 10.5. Excerpt(s): This application is a continuation in part of U.S. Ser. No. 09/972,008 filed on Oct. 4, 2001, which is a continuation in part of U.S. Ser. No. 09/738,410 filed on Dec. 14, 2000, which is a continuation in part of U.S. Ser. No. 09/569,889 filed on May 11, 2000, which is a continuation in part of U.S. Ser. No. 09/465,098 filed on Dec. 16, 1999; and is a continuation in part of U.S. Ser. No. 09/738,395 filed on Dec. 14, 2000, which is a continuation in part of U.S. Ser. No. 09/607,892 filed Jun. 30, 2000, now abandoned. This invention relates generally to methods and pharmaceutical formulations for skin lightening to treat skin hyperpigmentation and other skin pigmentation disorders. More specifically, this invention relates to compositions that comprise (a) an active agent useful in the treatment of skin hyperpigmentation when applied topically, and (b) an agent that enhances the permeability of skin or mucosal tissue to the active agent. Cosmetically disfiguring skin pigmentation irregularities and disorders are common and widespread, leading to a large demand for skin lightening products. These products are applied topically to the affected areas of skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with hyperpigmentation, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “hyperpigmentation” (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 hyperpigmentation. You can also use this procedure to view pending patent applications concerning hyperpigmentation. 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 5. BOOKS ON HYPERPIGMENTATION Overview This chapter provides bibliographic book references relating to hyperpigmentation. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hyperpigmentation 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 “hyperpigmentation” (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 hyperpigmentation: •

Atlas of Diseases of the Oral Cavity in HIV Infection Source: Copenhagen, Denmark: Munksgaard. 1995. 152 p. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail: [email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 400,000 plus postage; contact directly for current price in US dollars. ISBN: 8716115090. Summary: This atlas of oral diseases in HIV infection depicts and describes the oral manifestations of HIV in three sections. The authors stress that oral manifestations are often the key to an initial clinical diagnosis of HIV infection. The introductory material discusses epidemiology, the global aspects of HIV seropositivity, predictions for the future, and the classification of oral lesions associated with HIV infection. The first

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section covers lesions strongly associated with HIV infection including candidiasis, hyperplasia, angular cheilitis, hairy leukoplakia, periodontal diseases, linear gingival erythema, necrotizing gingivitis, stomatitis and periodontitis, Kaposi's sarcoma, and non-Hodgkin's lymphoma. The second section covers lesions less commonly associated with HIV infection including tuberculosis, hyperpigmentation, pigmentation of the nails, enlargement of major salivary glands, lymphoepithelial lesion, thrombocytopenia, atypical ulceration, herpes labialis, herpetic stomatitis, herpes zoster, varicella, condyloma acuminatum, focal epithelial hyperplasis, and verruca vulgaris. The third section outlines lesions seen in HIV infection, notably Klebsiella pneumonia infection, bacillar epithelioid angiomatosis, toxic epidermal necrolysis, drug-induced ulcerations, cryptococcoses, mucormycosis, penicilliosis, facial nerve paralysis, aphthous ulceration, cytomegalovirus-induced oral ulceration, and molluscum contagiosum. A final section describes other lesions, including exfoliative cheilitis, impetigo contagiosa, secondary syphilis, lichenoid lesions of buccal mucosa, and oral cancer. The atlas depicts each manifestation with a full-color photograph and provides brief descriptions. The book concludes with a list of references, coding according to the international classification of diseases, and a subject index. 111 figures. 193 references. •

Oral Symptoms and Signs Source: in Scully, C. Handbook of Oral Disease: Diagnosis and Management. New York, NY: Thieme New York. 2001. p.1-38. 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 oral symptoms and signs 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 normal facial sensation, anesthesia (complete loss of facial sensation), hypoaesthesia (partial loss of facial sensation), dry mouth (xerostomia), halitosis (bad breath), hyperpigmentation (discoloration of the oral mucosa), loss of elasticity of oral tissues, lumps and swellings, orofacial pain, paralysis, purpura (bleeding into the skin and mucosa), red and bluish lesions, salivary gland swelling, sialorrhea (excessive saliva or drooling), staining (tooth discoloration), taste disturbances, ulcers and erosions, and white lesions. 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 format for ease of reference. Full color photographs illustrate the more common conditions. 31 figures. 14 tables. 7 references.

Chapters on Hyperpigmentation In order to find chapters that specifically relate to hyperpigmentation, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hyperpigmentation 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

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“hyperpigmentation” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hyperpigmentation: •

Gastrointestinal Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 173-196. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: This chapter on gastrointestinal disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include disorders affecting the teeth, including teething, discoloration of teeth, odontogenic infections, fascial space infections, and necrotizing fasciitis; disorders affecting the oral mucosa, including oral ulcers, recurrent aphthae (recurrent aphthous stomatitis, or RAS), white and red lesions, desquamative gingivitis, and oral hyperpigmentation; dry mouth (xerostomia), including that due to Sjogren's syndrome; HIV infection; sialorrhea (excessive salivation); salivary gland swellings; Frey's syndrome; lumps in the neck; cervical lymph node enlargement; halitosis (bad breath); disturbed taste sensation; congenital disorders; esophageal disease, including dysphagia (difficulty in swallowing), and reflux esophagitis; problems of the stomach, including peptic ulcer and cancer of the stomach; disorders of the small intestine, including celiac disease (gluten sensitive enteropathy), dermatitis herpetiformis, linear IgA disease, and Crohn's disease (regional enteritis or ileitis); disorders of the pancreas, including acute pancreatitis, chronic pancreatitis, pancreatic tumors, and pancreatic transplantation; and disorders of the large intestine, including ulcerative colitis, diverticular disease, irritable bowel syndrome (IBS or spastic colon), familial polyposis, carcinoma of the colon, and antibiotic-associated (pseudomembranous) colitis. For each disease, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 figure. 12 tables. 96 references.

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Intraoral Coloured or Pigmented Lesions Source: in Scully, C. and Cawson, R.A. Oral Disease: Colour Guide. 2nd ed. Edinburgh, Scotland: Churchill Livingstone. 1999. p. 73-88. Contact: Available from W.B. Saunders Company, A Harcourt Health Sciences Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St Louis, MO 63146-9988. (800) 545-2522. Fax (800) 568-5136. E-mail: [email protected]. Website: www.wbsaunders.com. PRICE: $19.95 plus shipping and handling. ISBN: 044306170X. Summary: This chapter on intraoral colored or pigmented lesions is from a book that is intended as an aid to oral medicine and the diagnosis and treatment of oral disease. The chapter includes 16 full color photographs of intraoral colored or pigmented lesions, with textual information accompanying them. Conditions covered are: hereditary hemorrhagic telangiectasia (HHT), scleroderma (systemic sclerosis), hemangioma, Sturge-Weber syndrome, radiation induced lesions, denture induced stomatitis, erythematous candidosis, erythroplasia (erythroplakia), Kaposi's sarcoma, purpura, racial pigmentation, Peutz-Jeghers syndrome, drug induced hyperpigmentation, amalgam tattoo, pigmented nevi, and malignant melanoma. For each condition, the text

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briefly covers incidence and etiology, clinical features, diagnosis and diagnostic tests, and treatment options. •

Oral Manifestations: Classification Source: in Greenspan, D., et al. AIDS and the Mouth. Copenhagen, Denmark: Munksgaard. 1992. p. 85-90. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail: [email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 516 plus postage; contact directly for current price in US dollars. ISBN: 8716103211. Summary: This chapter on the classification of oral manifestations of HIV infection is from a medical textbook on the diagnosis and management of oral lesions related to AIDS. The authors define and classify fungal infections including candidiasis, histoplasmosis, cryptococcoses, and geotrichosis; bacterial infections including necrotizing gingivitis and progressive periodontitis, mycobacterium avium intracellular, actinomycosis, cat-scratch disease, Klebsiella pneumoniae infection, Enterobacter cloacae, Escherichia coli, exacerbation of apical periodontitis, sinusitis, and submandibular cellulitis; viral infections including herpetic stomatitis, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, and papillomavirus lesions; neoplasms including Kaposi's sarcoma, non-Hodgkin's lymphoma, and squamous cell carcinoma; neurologic disturbances including trigeminal neuropathy and facial palsy; and oral manifestations of unknown cause, including recurrent aphthous ulceration (RAU), progressive necrotizing ulceration, toxic epidermolysis (Lyell's syndrome), delayed wound healing, idiopathic thrombocytopenia, salivary gland enlargement, xerostomia, and oral mucosal hyperpigmentation. The authors note that this classification system is designed to be used in epidemiologic studies. 2 tables. 6 references.

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Intraoral Manifestations Associated with HIV Disease Source: in Glick, M., ed. Dental Management of Patients with HIV. Carol Stream, IL: Quintessence Publishing Company, Inc. 1994. p. 153-182. Contact: Available from Quintessence Publishing Company, Inc. 551 North Kimberly Drive, Carol Stream, IL 60188-1881. (800) 621-0387 or (630) 682-3223; Fax (630) 682-3288; E-mail: [email protected]; http://www.quintpub.com. PRICE: $68.00 plus shipping and handling. ISBN: 0867152885. Summary: This chapter on the intraoral manifestations associated with HIV disease is from a comprehensive textbook on the dental management of patients with HIV. The author surveys the intraoral manifestations common to persons with HIV disease, emphasizing the clinical appearance of the lesions, the significance of the lesions as markers for immune deterioration and disease progression, and treatment modalities for these lesions. Intraoral manifestations can be recognized by clinical appearance, histologic characteristics, and causative pathogens. For lesions to be considered specific to HIV disease, they need to appear more frequently, manifest more severely, or respond differently to therapy compared to other patient populations. The author discusses superficial fungal infections, deep-seated fungal infections, viral infections, bacterial infections, neoplasms, and miscellaneous lesions, including hyperpigmentation, aphthous ulcers, and necrotizing stomatitis. 22 figures. 5 tables. 117 references. (AA-M).

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Oral Manifestations of Unknown Etiology Source: in Greenspan, D., et al. AIDS and the Mouth. Copenhagen, Denmark: Munksgaard. 1992. p. 148-155. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail: [email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 516 plus postage; contact directly for current price in US dollars. ISBN: 8716103211. Summary: This chapter, from a medical textbook on the diagnosis and management of oral lesions related to AIDS, discusses oral manifestations of unknown etiology that are associated with AIDS. Oral manifestations discussed include recurrent aphthous ulceration (RAU), progressive necrotizing ulceration, toxic epidermolysis (Lyell's syndrome), delayed wound healing, idiopathic thrombocytopenia, salivary gland enlargement, xerostomia, and oral mucosal hyperpigmentation. Full-color photographs illustrate most of the manifestations described. 9 figures. 19 references.

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Whipple's Disease Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1854-1863. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Whipple's disease is a chronic systemic infection by a gram-positive bacterium, Tropheryma whippelii. The small intestine is most often affected, but a variety of other organs may also be involved, including the joints, the cardiovascular system, and the central nervous system (CNS). The clinical symptoms and findings include weight loss, diarrhea, malabsorption, fever, arthralgias, skin hyperpigmentation, and dementia. Treatment with antibiotics usually leads to clinical remission. This chapter on Whipple's disease is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include history, epidemiology, microbiology, immunology, and pathogenesis, clinical manifestations, pathology, diagnosis, differential diagnosis, treatment, and prognosis. The chapter includes a mini-outline with page citations, illustrations, and extensive references. 6 figures. 1 table. 113 references.

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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 Institute7: •

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

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

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

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

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

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

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

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

7

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.8 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:9 •

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

8

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). 9 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 Gateway10 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.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hyperpigmentation” (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 6625 7 24 24 233 6913

HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 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.14 Simply search by “hyperpigmentation” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

10

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

11

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). 12 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 13 14

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 Biologists15 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.16 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.17 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/.

15 Adapted 16

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. 17 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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

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

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Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Facial Injuries and Disorders http://www.nlm.nih.gov/medlineplus/facialinjuriesanddisorders.html Infant and Toddler Health http://www.nlm.nih.gov/medlineplus/infantandtoddlerhealth.html Mouth Disorders http://www.nlm.nih.gov/medlineplus/mouthdisorders.html Skin Aging http://www.nlm.nih.gov/medlineplus/skinaging.html Skin Diseases http://www.nlm.nih.gov/medlineplus/skindiseases.html Skin Pigmentation Disorders http://www.nlm.nih.gov/medlineplus/skinpigmentationdisorders.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 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 hyperpigmentation. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

Patient Resources

•

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

•

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

•

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

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

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option “Organization Resource Sheet.” Type “hyperpigmentation” (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 “hyperpigmentation” (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.18

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

18

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)19: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

19

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

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

•

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

•

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

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HYPERPIGMENTATION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] 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] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] 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] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH]

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Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Albinism: General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaptonuria: An inborn error of amino acid metabolism resulting from a defect in the enzyme homogentisate 1,2-dioxygenase and causing an accumulation of homogentisic acid in the urine. The condition is characterized by ochronosis in various tissues and arthritis. [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] 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] Alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] 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 organic matter fossilized in amber. [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 Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] 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] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH]

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Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal 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 hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] 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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticonvulsive: An agent that prevents or relieves convulsions. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are

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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] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aphthous Stomatitis: Inflammation of the mucous membrane of the mouth. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH]

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Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic Eczema: Generic term for acute or chronic inflammatory conditions of the skin, typically erythematous, edematous, papular, vesicular, and crusting; often accompanied by sensations of itching and burning. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [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] Auscultation: Act of listening for sounds within the body. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Avian: A plasmodial infection in birds. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus

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and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzoyl Peroxide: A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy. It is used also as a bleach in the food industry. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] 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] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH]

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Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body 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] 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] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [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] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush,

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def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

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] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]

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

Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Abnormalities: Congenital structural abnormalities of the cardiovascular system. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [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] 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] Cat-Scratch Disease: A self-limiting bacterial infection of the regional lymph nodes caused by Afipia felis, a gram-negative bacterium recently identified by the Centers for Disease Control and Prevention and by Bartonella henselae. It usually arises one or more weeks following a feline scratch, with raised inflammatory nodules at the site of the scratch being the primary symptom. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as

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metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [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] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] 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

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the passage of blood vessels and a nerve. [NIH] Chloasma: Melasma c. hepaticum a term formerly used to refer to circumscribed facial hyperpigmentation resembling melasma that may occur as a cutaneous manifestation of chronic liver disease. [EU] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] 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] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in

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mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [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

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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] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments,

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etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]

Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]

Cutaneous: Having to do with the skin. [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] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [NIH]

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Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depth Perception: Perception of three-dimensionality. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatologic Agents: Drugs used to treat or prevent skin disorders or for the routine care of skin. [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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnosis, Differential: Determination of which one of two or more diseases or conditions a patient is suffering from by systematically comparing and contrasting results of diagnostic measures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] 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]

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Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [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] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Eruptions: Adverse cutaneous reactions caused by ingestion, parenteral use, or local application of a drug. These may assume various morphologic patterns and produce various types of lesions. [NIH] Drusen: Tiny yellow or white deposits in the retina or optic nerve head. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphagia: Difficulty in swallowing. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH]

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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emetic: An agent that causes vomiting. [EU] Emetine: The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein syntheis in eucaryotic but not prokaryotic cells. [NIH] Emollients: Oleagenous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. [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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting

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the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Enhancer: Transcriptional element in the virus genome. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erbium: Erbium. An element of the rare earth family of metals. It has the atomic symbol Er, atomic number 68, and atomic weight 167.26. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH]

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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] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [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] Exfoliation: A falling off in scales or layers. [EU] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracorporeal: Situated or occurring outside the body. [EU] Extreme obesity: A body mass index [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU]

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Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] 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] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]

Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flexor: Muscles which flex a joint. [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] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH]

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Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungicide: An agent that destroys fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

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

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal stromal tumor: GIST. A type of tumor that usually begins in cells in the wall of the gastrointestinal tract. It can be benign or malignant. [NIH] Gastrointestinal tract: The stomach and intestines. [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]

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]

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Genitals: Sex organs, including the penis and testicles in men and the vagina and vulva in women. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Geotrichosis: Infection due to the fungus Geotrichum. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Gluten Sensitive Enteropathy: A general term that refers to celiac disease and dermatitis herpetiformis. [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] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of

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peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heliotherapy: Sunbathing as a therapeutic measure. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] 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] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatomegaly: Enlargement of the liver. [NIH]

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Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] 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] 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] Hypertelorism: Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH]

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Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [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] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [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] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] 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] Idiopathic: Describes a disease of unknown cause. [NIH] Ileitis: Inflammation of the ileum. [EU] Ileum: The lower end of the small intestine. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH]

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Immunoglobulin: A protein that acts as an antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] 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] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [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]

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]

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Ingestion: Taking into the body by mouth [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interorbital: Between the orbits. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ipecac: A syrup made from the dried rhizomes of two different species, Cephaelis ipecacuanha and C. acuminata, belonging to the Rubiaciae family. They contain emetine, cephaeline, psychotrine and other isoquinolines. Ipecac syrup is used widely as an emetic acting both locally on the gastric mucosa and centrally on the chemoreceptor trigger zone. [NIH]

Ipsilateral: Having to do with the same side of the body. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH]

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Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] 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] Lacrimal: Pertaining to the tears. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH]

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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] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] 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]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH]

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Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] 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] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [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] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanophores: Chromatophores (large pigment cells of fish, amphibia, reptiles and many invertebrates) which contain melanin. Short term color changes are brought about by an active redistribution of the melanophores pigment containing organelles (melanosomes).

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Mammals do not have melanophores; however they have retained smaller pigment cells known as melanocytes. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]

Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

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] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microscopy, Electron: Visual and photographic microscopy in which electron beams with wavelengths thousands of times shorter than visible light are used in place of light, thereby allowing much greater magnification. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH]

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Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] 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] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Mycobacterium avium: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans. [NIH] 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] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of

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some cancer treatments. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neodymium: Neodymium. An element of the rare earth family of metals. It has the atomic symbol Nd, atomic number 60, and atomic weight 144.24, and is used in industrial applications. [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] 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] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] 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] 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] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in

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the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ochronosis: Deposition of polymerized homogentisic acid as a brown-black pigment in the connective tissue. It occurs in alkaptonuria, but has also been observed in connection with exposure to certain chemicals (e.g., phenol, trinitrophenol, benzene derivatives). [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Onchocerciasis: Infection with nematodes of the genus Onchocerca. Characteristics include the presence of firm subcutaneous nodules filled with adult worms, pruritus, and ocular lesions. [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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [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 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] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [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] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]

Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum;

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lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of

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oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [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] Paralysis: Loss of ability to move all or part of the body. [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] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptic Ulcer Hemorrhage: Bleeding from a peptic ulcer. [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] Perianal: Located around the anus. [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.

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[NIH]

Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH]

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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] Photochemotherapy: Therapy using oral or topical photosensitizing agents with subsequent exposure to light. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [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]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the

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surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [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] Polycythemia Vera: A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [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] 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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by

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thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] 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] 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] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU]

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Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional enteritis: Inflammation of the intestines, but usually only of the small intestine. Also called Crohn's disease. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [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

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remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [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] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] 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] 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]

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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] Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [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] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] 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] Sclerotherapy: Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels. [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] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [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] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] 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] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] 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 Pigmentation: Coloration of the skin. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] 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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall

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in contrast to the viscera. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated 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

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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 Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stereoscopic: Accurate depth perception in the presence of binocular single vision, due to the slight disparity in the two retinal images of the same object. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [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]

Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH]

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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] 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] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] 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] Thermal: Pertaining to or characterized by heat. [EU] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [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] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either

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side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is

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motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] 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] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] 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

Dictionary 159

which a fetus develops. Also called the womb. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Varicella: Chicken pox. [EU] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [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] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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]

160

Hyperpigmentation

Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [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] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] 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] 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] 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] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH]

161

INDEX A Abdominal, 109, 135, 143, 145, 158 Abdominal Pain, 109, 135, 158 Abortion, 109, 132 Acantholysis, 109, 144 Acanthosis Nigricans, 5, 18, 48, 109 Acidosis, 35, 109 Acne, 68, 72, 73, 74, 109, 115 Acne Vulgaris, 73, 74, 109 Acquired Immunodeficiency Syndrome, 20, 39, 49, 109 Actinomycosis, 86, 109 Adaptability, 109, 118 Adaptation, 109, 119 Adenocarcinoma, 63, 109 Adenosine, 110, 111, 146 Adolescence, 5, 110 Adrenal Glands, 110, 111 Adrenal insufficiency, 14, 15, 110 Adrenergic, 110, 111, 113, 124, 126 Adverse Effect, 110, 153 Aerobic, 110, 140 Afferent, 110, 128 Agoraphobia, 110, 133, 144 Agranulocytosis, 7, 110 Albinism, 8, 110 Algorithms, 110, 115 Alkaline, 109, 110, 111, 116, 145 Alkaptonuria, 110, 142 Allylamine, 110, 111 Alpha Particles, 110, 150 Alpha-1, 110, 111 Alpha-helix, 110, 136 Alpha-Linolenic Acid, 56, 63, 66, 110 Alternative medicine, 110 Alveolitis, 29, 111 Amber, 111, 134 Ameliorating, 75, 111 Amine, 79, 111 Amino Acid Substitution, 8, 111 Amiodarone, 16, 19, 29, 41, 111 Amitriptyline, 48, 111 Ammonia, 111 Amyloidosis, 34, 40, 46, 111 Anaemia, 15, 111, 138 Anal, 111, 126 Analog, 71, 77, 111, 128 Anaplasia, 111

Anaplastic, 64, 112 Anatomical, 7, 112, 114, 118, 125, 134, 152 Anemia, 16, 23, 27, 31, 60, 112, 128 Anesthesia, 34, 84, 112 Animal model, 14, 112 Anomalies, 9, 43, 112, 156 Anthracycline, 112, 122 Antianginal, 111, 112 Antiarrhythmic, 111, 112 Antibacterial, 112, 154 Antibiotic, 85, 112, 116, 122, 124, 127, 139, 152, 154, 156 Antibodies, 112, 114, 138, 146 Antibody, 48, 112, 120, 134, 140 Anticholinergic, 111, 112 Anticonvulsive, 7, 112 Antiemetic, 112, 113, 119 Antigen, 31, 112, 120, 132, 134 Antimetabolite, 112, 128 Antimicrobial, 74, 112, 124 Antineoplastic, 112, 115, 124, 128, 132, 147, 156, 158, 159 Antioxidant, 112, 143 Antipsychotic, 113, 119 Antiviral, 113, 135 Anus, 111, 113, 120, 144 Aphthous Stomatitis, 4, 85, 113 Apoptosis, 33, 113 Aqueous, 113, 122, 125, 136 Arachidonic Acid, 113, 148 Archaea, 113, 139 Arterial, 110, 113, 121, 132, 149, 156 Arteries, 113, 116, 122, 139, 149 Arthralgia, 3, 113 Articular, 113, 143 Ascites, 113, 142 Asymptomatic, 6, 15, 114, 143 Ataxia, 23, 114, 156 Atopic, 46, 114 Atopic Eczema, 46, 114 Atrial, 111, 114, 121, 157 Atrioventricular, 114, 121 Atrium, 114, 121, 157, 159 Atrophy, 10, 11, 32, 78, 109, 114, 127 Atypical, 84, 114 Auditory, 9, 114 Auscultation, 11, 114 Autoantibodies, 114, 123

162

Hyperpigmentation

Autodigestion, 114, 143 Autosuggestion, 114, 133 Avian, 11, 114 B Bacteria, 109, 112, 113, 114, 127, 129, 130, 131, 139, 140, 154, 155, 156, 159 Bacterial Infections, 4, 86, 114 Bacteriostatic, 114, 127 Bacterium, 87, 114, 117, 131, 140 Basal Ganglia, 113, 114, 129 Basal Ganglia Diseases, 114 Basophils, 110, 114, 131, 137 Benign, 115, 117, 129, 141, 144 Benzene, 115, 142 Benzoyl Peroxide, 45, 115 Bilateral, 10, 20, 115, 127 Bile, 115, 129, 137 Bile duct, 115 Biliary, 87, 115, 143 Biliary Tract, 115, 143 Binding Sites, 11, 115 Biochemical, 61, 112, 115, 136, 143, 149, 153 Biopsy, 4, 115, 144 Biopsy specimen, 4, 115 Biosynthesis, 8, 113, 115, 158 Biotechnology, 12, 93, 115 Bladder, 8, 115, 120, 129, 158 Bleomycin, 19, 23, 27, 61, 115 Blister, 115, 144 Bloating, 115, 135 Blood Coagulation, 115, 116 Blood Glucose, 115, 131, 133, 135 Blood Platelets, 115, 153, 156 Blood pressure, 11, 116, 118, 132, 133, 140, 149 Blood vessel, 116, 117, 118, 119, 121, 131, 136, 138, 153, 156, 159 Blood Volume, 116, 147 Blood-Brain Barrier, 116, 137 Body Mass Index, 116, 127 Bone Marrow, 115, 116, 122, 138, 140, 147, 153, 155, 156 Bowel, 111, 116, 123, 135, 136, 145, 155, 158 Broad-spectrum, 116, 152 Buccal, 84, 116, 132, 137, 155 Buccal mucosa, 84, 116 Bullous, 61, 116, 123 Burns, 24, 115, 116 C Calcium, 7, 116, 120

Calcium channel blocker, 7, 116 Calcium Channel Blockers, 7, 116 Callus, 116, 125, 136 Candidiasis, 84, 86, 116 Candidosis, 85, 117 Carbon Dioxide, 30, 117, 146, 151 Carcinogen, 117, 140, 156, 158 Carcinogenic, 115, 117, 148 Carcinoid, 20, 50, 117 Carcinoma, 74, 85, 117 Cardiac, 6, 11, 60, 110, 112, 117, 121, 125, 126, 129, 141 Cardiomyopathy, 6, 9, 117 Cardiovascular, 9, 11, 87, 117, 153 Cardiovascular Abnormalities, 9, 117 Cardiovascular System, 87, 117 Carotene, 117, 151 Case report, 14, 33, 43, 52, 62, 63, 117 Cat-Scratch Disease, 86, 117 Causal, 6, 117, 126 Cecum, 117, 136 Celiac Disease, 85, 117, 130 Cell Cycle, 117, 119, 127, 131 Cell Death, 10, 113, 117, 127, 141 Cell Differentiation, 118, 155 Cell Division, 114, 117, 118, 127, 139, 146 Cell membrane, 116, 118, 145 Cell motility, 118, 131 Cell proliferation, 8, 118 Cellulitis, 86, 118 Central Nervous System, 87, 115, 118, 125, 129, 137, 142, 153 Cerebellar, 114, 118, 150 Cerebral, 114, 116, 118, 121, 126, 154 Cerebral Cortex, 114, 118 Cerebral Palsy, 118, 154 Cerebrovascular, 114, 116, 118, 156 Ceroid, 118, 137 Cervical, 74, 85, 118 Cervix, 109, 118 Character, 10, 118, 123, 130 Cheilitis, 84, 118 Chelation, 62, 118 Chemoreceptor, 113, 118, 135 Chemotherapy, 17, 24, 31, 40, 44, 48, 64, 118 Chin, 65, 118, 139 Chloasma, 72, 75, 119 Chlorpromazine, 14, 35, 53, 119 Cholinergic, 111, 113, 119 Choroid, 119, 151 Chromatin, 113, 119, 126, 141, 154

163

Chromosomal, 119, 140 Chromosome, 13, 25, 119 Chronic, 17, 26, 61, 62, 85, 87, 109, 114, 119, 123, 127, 134, 136, 140, 143, 144, 149, 150, 152, 153, 155, 158, 160 Cirrhosis, 3, 5, 6, 119, 131 CIS, 119, 151 Cisplatin, 33, 41, 119 C-kit receptor, 119, 155 Clinical Medicine, 63, 119, 148 Clinical trial, 7, 93, 119, 122, 150 Cloning, 115, 119 Cohort Studies, 119, 126 Colitis, 62, 85, 119, 135 Collagen, 33, 73, 111, 119, 128, 148 Colloidal, 60, 120, 145 Colon, 85, 119, 120, 128, 135, 136, 158 Combination chemotherapy, 22, 120 Complement, 120 Complementary and alternative medicine, 59, 66, 120 Complementary medicine, 59, 120 Compliance, 10, 120 Compress, 62, 120 Computational Biology, 93, 120 Condyloma, 84, 121 Cones, 121, 151 Congenita, 40, 121 Congestion, 113, 121, 126 Conjugated, 121, 122 Conjunctiva, 121, 157 Connective Tissue, 116, 118, 120, 121, 123, 128, 137, 142, 145, 151, 152 Consciousness, 121, 123 Constipation, 113, 121, 135 Contact dermatitis, 16, 62, 121 Contraindications, ii, 121 Convulsions, 32, 112, 121 Cor, 14, 121 Cornea, 121, 155, 160 Corneum, 121, 126, 133 Coronary, 121, 122, 139 Coronary Thrombosis, 122, 139 Cortex, 122, 127, 150 Cranial, 122, 128, 142, 145, 154, 157 Cribriform, 43, 122 Cross-Sectional Studies, 122, 126 Cryosurgery, 44, 122 Cyclosporine, 7, 122 Cytochrome, 69, 122 Cytomegalovirus, 84, 86, 122

Cytoplasm, 113, 115, 118, 122, 126, 131, 140, 141 Cytotoxic, 46, 122, 134 Cytotoxicity, 110, 119, 122 D Daunorubicin, 24, 122, 124 Deferoxamine, 19, 122 Degenerative, 123, 131, 138, 143 Deletion, 13, 113, 123 Dementia, 87, 109, 113, 123 Dendritic, 123, 138 Depigmentation, 11, 71, 123, 160 Depth Perception, 123, 155 Dermal, 17, 36, 49, 123, 137 Dermatitis, 16, 17, 26, 34, 61, 62, 74, 85, 123, 130 Dermatitis Herpetiformis, 85, 123, 130 Dermatologic Agents, 123, 125 Dermatosis, 62, 123 Dermis, 123, 151 Desensitization, 123, 134 Diabetes Mellitus, 5, 6, 123, 130, 131 Diagnosis, Differential, 87, 123 Diagnostic procedure, 67, 123, 145 Diarrhea, 87, 123, 125, 135 Diarrhoea, 123, 132 Diastolic, 123, 132 Diffusion, 123, 134, 151 Digestion, 115, 116, 123, 135, 137, 144, 155 Digestive system, 123, 140 Digestive tract, 124, 153, 154 Digitalis, 124, 143 Dilated cardiomyopathy, 11, 124 Direct, iii, 7, 119, 124, 150 Discrete, 10, 124, 137, 149, 160 Disparity, 124, 155 Distal, 28, 124 Dopa, 124, 137 Dopamine, 113, 119, 124, 137, 141, 145 Dorsal, 124, 127, 147 Doxorubicin, 21, 32, 39, 124 Doxycycline, 19, 124 Drive, ii, vi, 4, 5, 55, 85, 86, 87, 124, 137 Drug Eruptions, 7, 124 Drusen, 10, 46, 124 Duct, 124, 127, 138, 152, 155 Duodenum, 115, 124, 144, 155 Dyskinesia, 43, 113, 124 Dysphagia, 85, 124 Dysplasia, 47, 74, 124 E Edema, 41, 121, 125, 140, 142, 158

164

Hyperpigmentation

Efferent, 125, 128 Efficacy, 10, 125 Ejaculation, 125, 152 Elastic, 125, 130 Elasticity, 73, 84, 125 Elastin, 73, 120, 125 Electrocardiogram, 47, 125 Electrons, 113, 125, 143, 150 Emaciation, 109, 125 Embryo, 11, 109, 118, 125 Embryogenesis, 125, 155 Emetic, 125, 135 Emetine, 125, 135 Emollients, 68, 79, 125 Emulsion, 68, 125 Enamel, 125, 136 Endocarditis, 117, 125 Enhancer, 11, 126, 151 Enteritis, 126 Environmental Health, 92, 94, 126 Environmental Pollutants, 11, 126 Enzymatic, 79, 111, 116, 117, 120, 126, 151 Enzyme, 6, 8, 11, 49, 69, 71, 79, 110, 111, 126, 130, 144, 152, 160 Eosinophilia, 126, 128 Eosinophils, 110, 126, 131, 137 Epidemic, 60, 126, 154 Epidemiologic Studies, 86, 126 Epidemiological, 60, 126 Epidermal, 8, 33, 49, 50, 75, 76, 84, 126, 136, 137, 138, 159 Epidermis, 8, 75, 76, 80, 109, 115, 121, 123, 126, 133, 136, 137, 144, 148, 149 Epidermoid carcinoma, 126, 154 Epigastric, 126, 143 Epinephrine, 110, 124, 126, 141, 158 Epithelial, 8, 10, 11, 84, 109, 126, 131, 144 Epithelial Cells, 10, 126, 131 Epithelium, 121, 126, 129, 135, 136, 144, 160 Erbium, 30, 126 Erythema, 7, 15, 29, 40, 84, 121, 126, 127, 158 Erythema Multiforme, 7, 127 Erythema Nodosum, 29, 127 Erythrocytes, 111, 112, 116, 127, 143, 150 Erythromycin, 7, 127 Esophageal, 85, 127, 152 Esophageal Varices, 127, 152 Esophagitis, 85, 127 Esophagus, 123, 124, 127, 144, 150, 155 Estradiol, 27, 127

Ether, 71, 113, 127 Etoposide, 61, 127 Eukaryotic Cells, 127, 142, 158 Evacuation, 121, 127, 136, 149 Exfoliation, 52, 127, 141 Exocrine, 127, 143 Exogenous, 26, 127 Extensor, 127, 149, 160 Extracorporeal, 62, 127 Extreme obesity, 13, 127 Extremity, 52, 127 F Facial, 15, 24, 34, 60, 64, 65, 73, 84, 86, 98, 119, 128 Facial Expression, 128 Facial Nerve, 84, 128 Familial polyposis, 85, 128 Family Planning, 93, 128 Fasciitis, 85, 128 Fat, 73, 113, 116, 117, 121, 128, 137, 151, 152, 153 Fatigue, 3, 6, 128, 131 Ferritin, 4, 6, 42, 128 Fibroblasts, 128 Fibrosarcoma, 128 Fibrosis, 11, 110, 128, 152 Flexor, 127, 128, 137 Fluorouracil, 32, 47, 52, 128 Folate, 28, 31, 128 Folic Acid, 128 Forearm, 116, 128 Friction, 28, 62, 128 Fundus, 10, 129 Fungi, 129, 136, 139, 156, 159, 160 Fungicide, 32, 129 Fungus, 116, 129, 130, 140 G Gallbladder, 109, 115, 123, 129 Ganglion, 129, 142, 160 Gas, 111, 117, 123, 129, 132, 135, 140, 141 Gastric, 63, 114, 129, 135, 144, 152 Gastric Juices, 129, 144 Gastric Mucosa, 129, 135 Gastrin, 129, 132 Gastrointestinal, 3, 5, 22, 63, 64, 85, 87, 117, 126, 129, 153, 155, 156 Gastrointestinal stromal tumor, 22, 129 Gastrointestinal tract, 3, 87, 129, 153 Gels, 72, 129 Gene, 5, 11, 21, 22, 115, 129, 142, 150, 151 Genetic testing, 4, 129 Genetics, 9, 13, 21, 25, 32, 51, 59, 129

165

Genitals, 121, 130 Genomics, 9, 130 Geotrichosis, 86, 130 Gingivitis, 84, 85, 86, 130 Gland, 5, 84, 85, 86, 87, 130, 137, 143, 146, 152, 155, 156 Glucose, 115, 123, 130, 131, 135 Glucose Intolerance, 123, 130 Glutathione Peroxidase, 130, 152 Gluten, 85, 117, 130 Gluten Sensitive Enteropathy, 85, 130 Glycine, 111, 130, 141 Glycoprotein, 8, 130 Glycoside, 130, 143 Gonads, 39, 130, 133 Governing Board, 130, 148 Grade, 11, 130 Grading, 10, 130 Graft, 130 Gram-negative, 117, 130, 151 Gram-positive, 87, 131, 140, 154, 155 Granulocytes, 110, 131, 160 H Habitat, 131, 140 Habitual, 118, 131 Hair follicles, 123, 131, 155, 160 Halitosis, 84, 85, 131 Heart failure, 3, 131, 142 Heliotherapy, 63, 131 Helix-loop-helix, 11, 131 Heme, 122, 131, 147, 158 Hemochromatosis, 3, 4, 5, 6, 62, 131 Hemoglobin, 112, 127, 131, 147 Hemolytic, 128, 131, 134 Hemorrhage, 131, 149 Hemorrhoids, 131, 152 Hepatic, 6, 125, 131, 147 Hepatitis, 26, 131 Hepatocyte, 49, 131 Hepatocyte Growth Factor, 49, 131 Hepatomegaly, 12, 131 Hereditary, 3, 4, 5, 43, 85, 132 Heredity, 109, 129, 132 Herpes, 50, 84, 132 Herpes Zoster, 84, 132 Hiccup, 119, 132 Hirsutism, 132, 133 Hormonal, 73, 114, 132 Hormone, 11, 14, 16, 74, 80, 126, 127, 129, 132, 135, 151, 156 Hydrogen, 109, 111, 130, 132, 137, 139, 141, 143, 149

Hydrolysis, 119, 132, 147 Hydroxylysine, 120, 132 Hydroxyproline, 111, 120, 132 Hydroxyurea, 33, 35, 39, 45, 132 Hyperglycemia, 6, 132 Hyperkeratosis, 7, 25, 132 Hyperplasia, 25, 74, 84, 132, 137 Hypersensitivity, 61, 123, 132, 151 Hypertelorism, 9, 132 Hypertension, 11, 71, 77, 116, 132, 158 Hyperthyroidism, 25, 133 Hypertrichosis, 41, 132, 133 Hypertrophic cardiomyopathy, 11, 133 Hypertrophy, 121, 132, 133, 157 Hypoglycemic, 6, 133 Hypoglycemic Agents, 6, 133 Hypogonadism, 6, 133 Hypopigmentation, 14, 17, 33, 34, 42, 133 Hypoplasia, 18, 133 Hypotension, 113, 121, 133 Hypotensive, 70, 77, 133 Hypothalamic, 13, 14, 133 Hypothalamus, 133, 146 I Iatrogenic, 5, 133 Ichthyosis, 52, 133 Idiopathic, 30, 86, 87, 133, 150 Ileitis, 85, 133 Ileum, 117, 133 Imipramine, 30, 31, 133 Immune response, 112, 133, 134, 155, 159 Immune system, 133, 134, 138, 160 Immunodeficiency, 4, 5, 109, 133 Immunoglobulin, 112, 134, 140 Immunology, 87, 134 Immunosuppressant, 128, 134 Immunosuppression, 5, 134, 138, 142 Immunosuppressive, 134 Immunosuppressive Agents, 134 Impairment, 114, 124, 134, 139 Impetigo, 84, 134 In situ, 8, 36, 134 In vitro, 8, 11, 24, 134 In vivo, 72, 134, 138 Incidental, 63, 134 Incision, 134, 135 Infarction, 122, 134, 139 Infiltration, 134, 160 Infusion, 134, 152 Ingestion, 62, 63, 75, 124, 131, 132, 135 Innervation, 128, 135 Inorganic, 119, 135, 140

166

Hyperpigmentation

Insulin, 5, 48, 135 Insulin-dependent diabetes mellitus, 135 Interferon, 26, 135 Interferon-alpha, 26, 135 Interorbital, 132, 135 Intestinal, 5, 28, 117, 135, 138 Intestinal Mucosa, 117, 135 Intestine, 116, 126, 135, 136, 155 Intracellular, 86, 116, 134, 135, 152 Intraocular, 135, 142 Intraocular pressure, 135, 142 Invasive, 7, 135 Ipecac, 62, 125, 135 Ipsilateral, 51, 135, 150 Iris, 71, 77, 121, 135 Irritable Bowel Syndrome, 85, 135 Irritants, 7, 136 Ischemia, 114, 136 K Kb, 92, 136 Keratin, 68, 136, 152 Keratinocytes, 8, 23, 68, 75, 76, 136 Keratolytic, 73, 136, 147 Keratolytic Agents, 73, 136 Keratosis, 46, 49, 60, 73, 109, 136 L Lacrimal, 128, 136 Large Intestine, 85, 117, 123, 124, 135, 136, 150, 153 Latent, 7, 136, 148 Laxative, 63, 136 Lectin, 64, 136 Leiomyosarcoma, 28, 136 Lens, 121, 136, 160 Lentigo, 44, 49, 50, 73, 74, 136 Leprosy, 36, 136 Lesion, 84, 136, 158 Leukemia, 124, 137 Leukocytes, 114, 116, 126, 131, 135, 137, 140, 141, 143 Leukocytosis, 137, 147 Leukoplakia, 84, 137 Levodopa, 28, 124, 137 Libido, 4, 137 Lichen Planus, 30, 33, 137 Lipid, 118, 135, 137, 143 Lipid Peroxidation, 137, 143 Lipofuscin, 10, 118, 137 Liver cancer, 6, 137 Localized, 8, 12, 26, 33, 36, 41, 73, 111, 132, 133, 134, 137, 140, 142, 146, 152, 158 Longitudinal Studies, 10, 122, 137

Loop, 137 Lumbar, 29, 137 Lupus, 48, 137 Lymph, 5, 63, 85, 118, 137, 138, 140, 150, 155 Lymph node, 63, 85, 118, 137, 138, 140, 150 Lymphadenopathy, 5, 137 Lymphatic, 134, 137, 138, 142, 153, 154 Lymphatic system, 137, 138, 153, 154 Lymphocyte, 109, 112, 134, 138 Lymphocyte Count, 109, 138 Lymphocyte Depletion, 134, 138 Lymphoid, 112, 138 Lymphoma, 61, 64, 84, 86, 138, 140 M Macula, 138 Macula Lutea, 138 Macular Degeneration, 10, 46, 138 Malabsorption, 31, 87, 117, 138 Malignancy, 40, 109, 138, 144 Malignant, 9, 14, 56, 85, 109, 112, 128, 129, 137, 138, 140, 141, 152 Malnutrition, 114, 138 Manifest, 9, 86, 138 Mastication, 138, 158 MEDLINE, 93, 138 Megaloblastic, 16, 27, 31, 60, 128, 138 Melanin, 8, 35, 59, 61, 64, 68, 69, 70, 73, 75, 76, 79, 80, 123, 133, 135, 138, 139, 145, 158 Melanocytes, 8, 9, 24, 68, 69, 71, 75, 76, 77, 80, 133, 138, 139, 141 Melanoma, 8, 18, 56, 61, 85, 138, 158 Melanophores, 138, 139 Melanosis, 7, 28, 56, 63, 64, 65, 80, 109, 139 Melanosomes, 68, 71, 75, 76, 77, 79, 138, 139 Membrane, 8, 10, 113, 118, 119, 120, 121, 127, 131, 139, 140, 142, 144, 145, 147, 151, 157, 160 Memory, 59, 123, 139 Meninges, 118, 139 Mental, iv, 7, 47, 92, 94, 118, 123, 128, 139, 149, 158 Mental Retardation, 47, 139 Metastasis, 139 Metastatic, 7, 56, 139 MI, 69, 70, 107, 139 Microbe, 139, 157 Microbiology, 87, 109, 114, 139 Microscopy, Electron, 29, 38, 139

167

Minocycline, 13, 17, 22, 29, 33, 36, 37, 38, 41, 44, 47, 48, 51, 139 Mitochondrial Swelling, 139, 141 Mitosis, 113, 139 Mitotic, 127, 139, 159 Modification, 8, 10, 111, 139, 150 Molecular, 8, 9, 25, 72, 93, 95, 111, 115, 121, 139, 157 Molecule, 112, 115, 120, 130, 132, 136, 139, 143, 150 Monitor, 10, 140, 142 Monoclonal, 46, 140 Monocytes, 31, 137, 140 Mononuclear, 128, 140 Morphological, 125, 129, 138, 140 Morphology, 11, 113, 140 Mosaicism, 25, 33, 140 Motor Activity, 121, 140 Mucins, 140, 152 Mucociliary, 140, 153 Mucocutaneous, 17, 35, 38, 39, 140 Mucosa, 4, 84, 85, 129, 137, 140, 155 Mucositis, 6, 140 Mucus, 140, 158 Mustard Gas, 136, 140 Mycobacterium, 26, 86, 136, 140, 152, 158 Mycobacterium avium, 86, 140, 152 Mycosis, 20, 38, 140 Mycosis Fungoides, 20, 140 Myeloma, 41, 140 Myelosuppression, 7, 140 Myocardium, 139, 141 N Necrolysis, 84, 141 Necrosis, 19, 113, 128, 134, 139, 141 Neodymium, 37, 141 Neoplasm, 141, 144, 152 Neoplastic, 111, 138, 141 Nerve, 110, 111, 112, 114, 119, 125, 128, 129, 135, 141, 142, 151, 152, 155, 157, 160 Nervous System, 110, 118, 141, 145 Neurologic, 5, 60, 86, 141 Neurons, 137, 141 Neuropathy, 86, 141 Neurotransmitter, 110, 111, 124, 130, 141, 155 Neutrons, 110, 141, 150 Neutrophils, 110, 131, 137, 141 Nevus, 39, 65, 73, 136, 141 Nitrogen, 111, 141, 158 Norepinephrine, 110, 111, 124, 141 Nuclear, 114, 125, 127, 129, 141, 142

Nucleus, 113, 114, 119, 122, 126, 127, 140, 141, 142, 149, 156 O Occult, 40, 142 Ochronosis, 26, 52, 110, 142 Ocular, 9, 70, 77, 142 Ocular Hypertension, 70, 77, 142 Oedema, 48, 142 Onchocerciasis, 52, 142 Oncogene, 131, 142, 155 Opportunistic Infections, 5, 109, 142 Opsin, 142, 151 Optic Nerve, 124, 142, 151 Optic nerve head, 124, 142 Oral Health, 85, 142 Oral Hygiene, 131, 142 Oral Manifestations, 4, 83, 86, 87, 142 Organelles, 122, 138, 139, 140, 142 Orofacial, 7, 84, 143 Osteoarthritis, 4, 143 Ouabain, 11, 143 Ovary, 127, 130, 143 Oxidation, 113, 122, 130, 137, 143 Oxidative Stress, 8, 59, 143 P Palate, 143, 155 Palsy, 86, 143 Pancreas, 85, 87, 109, 123, 131, 135, 143 Pancreatic, 85, 143 Pancreatitis, 85, 143 Pancytopenia, 28, 143 Panic, 133, 143 Panic Disorder, 133, 143 Papillary, 132, 144 Papilloma, 121, 144 Papillomavirus, 86, 144 Paralysis, 84, 144, 154 Parenteral, 124, 144 Parkinsonism, 113, 137, 144 Partial remission, 144, 150 Patch, 137, 144 Pathogenesis, 5, 87, 144 Pathologic, 5, 109, 113, 115, 117, 122, 132, 144, 149 Pathologic Processes, 113, 144 Pathophysiology, 5, 6, 87, 144 Pelvis, 136, 137, 144, 158 Pemphigus, 37, 109, 144 Pepsin, 144 Peptic, 85, 144, 152 Peptic Ulcer, 85, 144, 152 Peptic Ulcer Hemorrhage, 144, 152

168

Hyperpigmentation

Peptide, 79, 80, 111, 136, 144, 147, 149, 150 Percutaneous, 72, 144 Perianal, 121, 144 Periodontal disease, 7, 84, 144 Periodontitis, 84, 86, 130, 144 Perioral, 30, 145 Peripheral blood, 135, 145 Peripheral Nerves, 136, 145 Peripheral Nervous System, 141, 143, 145, 155 Peritoneal, 87, 113, 142, 145 Peritoneal Cavity, 113, 142, 145 Peritoneum, 145 Peroxide, 115, 130, 137, 145 Petrolatum, 17, 125, 145 Petroleum, 145 Phagocytosis, 10, 145 Pharmacologic, 17, 112, 145, 157 Phenolphthalein, 125, 145 Phenylalanine, 145, 158 Phlebotomy, 5, 6, 145 Phospholipids, 128, 145 Phosphorus, 116, 146 Photochemotherapy, 26, 146 Photoreceptors, 10, 121, 146 Photosensitivity, 41, 146, 147 Photosensitizing Agents, 146 Phototherapy, 76, 146 Physical Examination, 6, 146 Physiologic, 115, 124, 146, 150 Pigment, 10, 11, 17, 49, 64, 68, 71, 75, 76, 77, 79, 80, 110, 118, 123, 137, 138, 142, 146 Pigmentation, 7, 9, 25, 34, 41, 43, 60, 64, 68, 71, 75, 76, 77, 80, 84, 85, 139, 146 Pituitary Gland, 74, 146, 152 Placenta, 127, 146 Plants, 110, 117, 124, 130, 136, 140, 142, 143, 146, 157 Plasma, 112, 116, 118, 130, 131, 140, 146, 152 Plasma cells, 112, 140, 146 Platelets, 140, 143, 146 Platinum, 119, 137, 146 Pleated, 136, 146 Pleural, 142, 146, 147 Pleural cavity, 142, 147 Pneumonia, 84, 121, 147 Podophyllotoxin, 127, 147 Polycythemia Vera, 39, 145, 147 Polypeptide, 111, 119, 147 Polyposis, 147

Polysaccharide, 112, 147 Porphyria, 28, 145, 147 Porphyria Cutanea Tarda, 28, 145, 147 Porphyria, Hepatic, 147 Porphyrins, 147 Posterior, 111, 114, 119, 124, 135, 143, 147, 154 Post-translational, 8, 147 Post-traumatic, 75, 147 Potentiating, 111, 147 Practice Guidelines, 94, 148 Precancerous, 72, 148 Precursor, 80, 113, 124, 126, 137, 141, 145, 148, 158 Predisposition, 74, 148 Premalignant, 74, 148 Prenatal, 125, 148 Prevalence, 5, 148 Prickle, 109, 136, 148 Progression, 4, 6, 10, 86, 112, 148 Progressive, 15, 20, 23, 25, 29, 43, 86, 87, 118, 119, 123, 141, 143, 148 Proline, 120, 132, 148 Promoter, 11, 25, 148 Promotor, 148, 151 Prophylaxis, 80, 148, 152 Prostaglandins, 71, 77, 110, 113, 148 Prostaglandins A, 71, 77, 148 Prostaglandins D, 148 Protective Agents, 116, 148 Protein C, 128, 136, 148 Protein Folding, 8, 149 Protein S, 115, 125, 127, 149, 156 Proteins, 9, 111, 112, 118, 119, 120, 127, 136, 139, 141, 144, 146, 149, 152, 153, 157, 159 Protons, 110, 132, 149, 150 Proxy, 62, 149 Pruritic, 123, 137, 149 Pruritus, 142, 149, 158 Psoriasis, 60, 64, 73, 74, 140, 146, 149 Psychiatric, 35, 149 Psychiatry, 23, 48, 149 Psychic, 137, 139, 149 Public Policy, 93, 149 Pulmonary, 9, 116, 121, 149, 159 Pulmonary Artery, 116, 149, 159 Pulmonary hypertension, 121, 149 Pulse, 140, 149 Purgative, 136, 149 Purpura, 84, 85, 149 Purulent, 149, 150, 159

169

Pustular, 109, 134, 149 Pyoderma, 36, 150 Pyoderma Gangrenosum, 36, 150 Q Quality of Life, 6, 150 Quaternary, 149, 150 Quiescent, 150, 160 R Race, 68, 124, 150 Radiation, 14, 68, 74, 85, 134, 150, 158, 160 Radiological, 144, 150 Randomized, 125, 150 Ras gene, 25, 150 Receptor, 11, 48, 70, 77, 109, 112, 118, 119, 124, 131, 150, 153 Rectum, 113, 120, 123, 124, 128, 129, 136, 150 Red blood cells, 127, 131, 140, 147, 150 Red Nucleus, 114, 150 Refer, 1, 116, 119, 120, 129, 132, 138, 141, 150 Reflux, 85, 150 Refraction, 150, 154 Refractory, 30, 150 Regimen, 125, 150, 151 Regional enteritis, 85, 150 Regional lymph node, 117, 150 Remission, 87, 150 Renal Dialysis, 29, 151 Respiration, 117, 118, 140, 151 Response Elements, 11, 151 Reticular, 52, 151 Retina, 10, 51, 119, 121, 124, 136, 138, 142, 151, 152, 160 Retinal, 10, 11, 124, 142, 151, 155 Retinoid, 69, 151 Retinol, 79, 151 Retreatment, 10, 151 Rhamnose, 143, 151 Rheumatism, 17, 151 Rheumatoid, 35, 151 Rheumatoid arthritis, 35, 151 Rhodopsin, 142, 151 Ribonucleoside Diphosphate Reductase, 132, 152 Rifabutin, 26, 152 Risk factor, 5, 10, 84, 126, 152 Rod, 114, 152 S Saliva, 84, 152 Salivary, 5, 84, 85, 86, 87, 122, 123, 128, 152, 153, 155, 160

Salivary glands, 84, 122, 123, 128, 152 Salivation, 85, 152 Sarcoma, 46, 84, 85, 86, 128, 152 Scatter, 152, 158 Scleroderma, 85, 128, 152 Scleroproteins, 136, 152 Sclerosis, 25, 29, 33, 38, 85, 152 Sclerotherapy, 19, 152 Screening, 4, 5, 6, 11, 119, 152 Sebaceous, 72, 74, 123, 136, 152, 160 Sebaceous gland, 74, 123, 136, 152, 160 Sebum, 109, 152 Secretion, 49, 109, 110, 135, 140, 152 Sedative, 111, 133, 152 Selenium, 25, 152 Sella Turcica, 146, 152 Semen, 65, 125, 152 Semisynthetic, 127, 139, 153 Senile, 73, 136, 153 Serotonin, 111, 113, 141, 153, 158 Serum, 4, 5, 6, 42, 120, 138, 153 Sex Characteristics, 110, 153 Shock, 153, 157 Sialorrhea, 84, 85, 153 Side effect, 68, 71, 72, 77, 110, 113, 140, 153, 157 Signs and Symptoms, 150, 153, 158 Sinusitis, 86, 153 Skeletal, 43, 47, 153 Skeleton, 153 Skin graft, 28, 153 Skin Pigmentation, 61, 80, 98, 153 Small intestine, 85, 87, 117, 124, 126, 132, 133, 135, 150, 153 Smooth muscle, 110, 116, 153, 155 Social Environment, 150, 153 Soft tissue, 84, 116, 128, 153 Solid tumor, 115, 124, 153 Somatic, 110, 125, 139, 145, 153 Spastic, 85, 135, 154 Specialist, 99, 154 Species, 11, 111, 124, 126, 135, 139, 140, 150, 154, 155, 156, 157, 158, 159, 160 Spectroscopic, 29, 154 Spectrum, 4, 5, 154 Sperm, 119, 154 Spermatozoa, 152, 154 Sphenoid, 132, 152, 154 Spinal cord, 118, 129, 139, 141, 145, 154 Spinous, 126, 136, 154 Spirochete, 154, 156 Spleen, 111, 122, 138, 147, 154

170

Hyperpigmentation

Splenomegaly, 147, 154 Sporadic, 147, 154 Squamous, 7, 86, 126, 154 Squamous cell carcinoma, 7, 86, 126, 154 Squamous cells, 154 Staphylococcus, 134, 139, 154, 155 Staphylococcus aureus, 134, 155 Stem Cell Factor, 13, 33, 49, 119, 155 Stenosis, 9, 155 Stereoscopic, 10, 155 Stimulus, 124, 135, 155, 156 Stomach, 85, 109, 114, 123, 124, 127, 129, 132, 144, 145, 150, 153, 154, 155 Stomatitis, 84, 85, 86, 155 Stool, 120, 135, 136, 155 Streptococci, 134, 155 Stress, 8, 73, 83, 135, 143, 148, 151, 155, 158 Stricture, 155 Stroma, 135, 155 Stromal, 155 Subacute, 134, 153, 155 Subclinical, 65, 134, 155 Subcutaneous, 118, 125, 142, 144, 155 Submandibular, 86, 155 Subspecies, 154, 155 Substance P, 127, 152, 155 Suppression, 8, 155 Suppurative, 118, 155 Symptomatic, 5, 143, 156 Syphilis, 84, 156 Systemic disease, 133, 156 Systolic, 132, 156 T Tear Gases, 136, 156 Teichoic Acids, 131, 156 Telangiectasia, 85, 156 Teratogenic, 11, 156 Teratogenicity, 11, 156 Testis, 127, 130, 156 Tetracycline, 124, 139, 156 Thalamic, 114, 156 Thalamic Diseases, 114, 156 Thermal, 74, 141, 156 Thiotepa, 39, 156 Thoracic, 29, 138, 156, 160 Thorax, 137, 156 Threshold, 132, 156 Thrombocytopenia, 5, 84, 86, 87, 156 Thrombosis, 149, 152, 156 Thrush, 116, 156 Thyroid, 11, 133, 156, 158 Thyroid Gland, 133, 156

Tone, 73, 142, 157 Tonus, 157 Topical, 26, 27, 35, 45, 61, 69, 70, 72, 73, 74, 75, 78, 79, 80, 145, 146, 157 Toxic, iv, 5, 7, 84, 86, 87, 115, 122, 124, 141, 147, 152, 156, 157 Toxicity, 7, 11, 60, 61, 157 Toxicology, 59, 60, 62, 94, 157 Toxins, 112, 134, 157 Trachea, 156, 157 Transcription Factors, 151, 157 Transfection, 115, 157 Translation, 111, 127, 157 Translational, 157 Translocation, 127, 157 Transplantation, 25, 85, 138, 157 Trauma, 75, 76, 114, 127, 133, 141, 143, 156, 157 Triad, 47, 157 Tricuspid Atresia, 121, 157 Tricyclic, 111, 133, 157 Trigeminal, 86, 157 Trigger zone, 113, 135, 158 Trophic, 15, 158 Tryptophan, 120, 153, 158 Tuberculosis, 84, 137, 140, 158 Tunica, 140, 158 Tyrosine, 8, 80, 124, 158 U Ubiquitin, 8, 158 Ulcer, 118, 144, 158, 159 Ulceration, 84, 86, 87, 144, 158 Ulcerative colitis, 85, 150, 158 Ultraviolet radiation, 8, 41, 146, 158 Uraemia, 143, 158 Urethane, 72, 158 Urethra, 158 Urine, 12, 110, 115, 158 Uroporphyrinogen Decarboxylase, 147, 158 Urticaria, 24, 34, 158 Uterus, 109, 118, 129, 136, 158, 159 V Vaccines, 159 Vagina, 117, 118, 130, 159 Vaginitis, 117, 159 Varicella, 84, 86, 159 Varicose, 152, 159 Varicose vein, 152, 159 Vascular, 13, 33, 38, 110, 111, 116, 119, 123, 134, 142, 146, 156, 158, 159 Vascular Resistance, 111, 159

171

Vasculitis, 143, 159 Vein, 142, 145, 159 Venereal, 156, 159 Venous, 19, 36, 131, 142, 149, 157, 159 Ventricle, 114, 121, 133, 149, 156, 157, 159 Ventricular, 22, 111, 121, 157, 159 Verruca, 23, 84, 159 Vesicular, 114, 123, 132, 159 Veterinary Medicine, 93, 159 Villous, 117, 159 Vinblastine, 61, 159 Vinca Alkaloids, 159 Vinorelbine, 64, 159 Viral, 4, 86, 159 Virulence, 157, 159 Virus, 4, 5, 26, 74, 86, 109, 126, 135, 159, 160 Viscera, 140, 154, 160 Vitiligo, 29, 45, 160 Vitreous, 136, 151, 160

Vitreous Body, 151, 160 Vitro, 160 Vivo, 138, 160 Vulgaris, 73, 84, 109, 160 W Wart, 136, 160 White blood cell, 112, 137, 138, 140, 146, 160 Windpipe, 156, 160 Wound Healing, 5, 86, 87, 160 X Xenograft, 112, 160 Xerostomia, 4, 5, 7, 84, 85, 86, 87, 160 X-ray, 29, 38, 51, 74, 142, 160 Y Yeasts, 117, 129, 160 Z Zoster, 86, 160 Zygote, 140, 160

172

Hyperpigmentation

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