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

PHENYTOIN 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., 1960Phenytoin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84544-1 1. Phenytoin-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 phenytoin. 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 PHENYTOIN............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Phenytoin .................................................................................... 10 The National Library of Medicine: PubMed ................................................................................ 30 CHAPTER 2. NUTRITION AND PHENYTOIN ..................................................................................... 75 Overview...................................................................................................................................... 75 Finding Nutrition Studies on Phenytoin..................................................................................... 75 Federal Resources on Nutrition ................................................................................................... 79 Additional Web Resources ........................................................................................................... 79 CHAPTER 3. CLINICAL TRIALS AND PHENYTOIN ........................................................................... 83 Overview...................................................................................................................................... 83 Recent Trials on Phenytoin.......................................................................................................... 83 Keeping Current on Clinical Trials ............................................................................................. 84 CHAPTER 4. PATENTS ON PHENYTOIN ........................................................................................... 87 Overview...................................................................................................................................... 87 Patents on Phenytoin................................................................................................................... 87 Patent Applications on Phenytoin ............................................................................................... 97 Keeping Current ........................................................................................................................ 101 CHAPTER 5. BOOKS ON PHENYTOIN ............................................................................................. 103 Overview.................................................................................................................................... 103 Book Summaries: Federal Agencies............................................................................................ 103 Book Summaries: Online Booksellers......................................................................................... 104 The National Library of Medicine Book Index ........................................................................... 104 Chapters on Phenytoin............................................................................................................... 105 CHAPTER 6. PERIODICALS AND NEWS ON PHENYTOIN ............................................................... 109 Overview.................................................................................................................................... 109 News Services and Press Releases.............................................................................................. 109 Newsletter Articles .................................................................................................................... 111 Academic Periodicals covering Phenytoin ................................................................................. 112 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 113 Overview.................................................................................................................................... 113 U.S. Pharmacopeia..................................................................................................................... 113 Commercial Databases ............................................................................................................... 114 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 117 Overview.................................................................................................................................... 117 NIH Guidelines.......................................................................................................................... 117 NIH Databases........................................................................................................................... 119 Other Commercial Databases..................................................................................................... 121 APPENDIX B. PATIENT RESOURCES ............................................................................................... 123 Overview.................................................................................................................................... 123 Patient Guideline Sources.......................................................................................................... 123 Finding Associations.................................................................................................................. 125 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 127 Overview.................................................................................................................................... 127 Preparation................................................................................................................................. 127 Finding a Local Medical Library................................................................................................ 127 Medical Libraries in the U.S. and Canada ................................................................................. 127 ONLINE GLOSSARIES................................................................................................................ 133

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Online Dictionary Directories ................................................................................................... 135 PHENYTOIN DICTIONARY ...................................................................................................... 137 INDEX .............................................................................................................................................. 209

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

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

Medically Induced Gingival Hyperplasia: Causes, Treatment, and Prevention Source: Consultant. 39(2): 359-360, 362. February 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. (203) 661-0600. Summary: Anticonvulsants (notably phenytoin), cyclosporine, and calcium channel blockers have diverse pharmacologic actions, but they all share the ability to induce overgrowth of the gingiva (gums). In this article, the authors summarize key details from their recent review article about the medications associated with gingival hyperplasia (overgrowth). The authors note that some degree of gingival hyperplasia occurs in up to 50 percent of patients who take one or more of these agents. When the condition is severe, speech, mastication, tooth eruption, and esthetic appearance may be

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affected adversely. The treatment of choice for medically induced gingival hyperplasia is discontinuation of the culprit medication. Even when this is not possible, sometimes substitution of another drug of the same class of medication may achieve the desired efficacy without inducing overgrowth. Referral to a dentist or periodontist is appropriate for patients who have gingival hyperplasia, and for those in whom the condition is anticipated. The patient's dentist or dental hygienist can provide specific and individualized instructions about daily maintenance care and can recommend individualized recall intervals for care in the dental office. 3 figures. 6 references. •

Medications as Risk Factors for Periodontal Disease Source: Journal of Periodontology. 67(10 Supplement): 1055-1059. October 1996. Summary: As the U.S. population ages, many people will take more medications that may benefit their general health but not necessarily their periodontal health. This article discusses medications as risk factors for periodontal diseases. The author groups the effects of medications into six categories: behavioral alteration of oral hygiene methods, alteration of plaque composition, effect on gingival tissues, effect on alveolar bone, effect on gingival crevicular fluid, and effect on salivary flow. Although most medications discussed in the article increase the risk for periodontal disease, a few may actually decrease the risk. These include the effect of phenytoin on alveolar bone, the antibacterial effect of antibiotics, the anticollagenolytic effects of tetracyclines, and the effect of nonsteroidal anti-inflammatory drugs on decreasing alveolar bone resorption. 66 references. (AA).

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Treatment of the Epileptic Patient in the Dental Office Source: New York State Dental Journal. 64(2): 26-31. February 1998. Contact: Available from Dental Society of the State of New York. 7 Elk Street, Albany, NY 12207. (518) 465-0044; Fax (518) 427-0461. Summary: Epilepsy is a relatively common problem in children, adults, and older adults. Dentists need to be familiar with the various manifestations of the disease, the anticonvulsant medications (AEDs) that patients are taking, and the complications and side effects of these drugs. In this article, the types of seizures and AEDs in common use are described, and the authors offer guidelines for treatment planning. Drugs covered include phenobarbital, Dilantin (phenytoin), Tegretol (carbamazepine), Depakene and Depakote (volproic acid and divalproex), Mysoline (primidone), Zarontine (ethosuximide), Lamictal (lamotrigine), Neurontin (gabapentin), Tranxene (clorazepate dipotassium), and Topamax (topiramate); the use of a ketosis diet to control seizures is also discussed. Recommendations are also provided for managing the patient who has a seizure in the dental office, with emergency protocols and referral guidelines noted. The authors emphasize that the well-controlled patient with epilepsy can be treated safely and comfortably in the average dental office. 1 table. 12 references.

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Trigeminal Neuralgia: A Dental Diagnosis Challenge Source: Northwest Dentistry. 78(3): 19-24. May-June 2000. Contact: Available from Minnesota Dental Association. 2236 Marshall Avenue, St. Paul, MN 55104. (800) 950-3368 or (651) 646-7454. Fax (651) 646-8246. E-mail: [email protected]. Website: mndental.org/nwdentistry.html. Summary: Perhaps one of the most perplexing diagnostic and treatment challenges facing the dental practitioner today is the situation presented by a patient complaining

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of toothache or sinusitis without any dental abnormality as its origin. This article reviews trigeminal neuralgia, focusing on its sometimes difficult diagnosis. The author notes that misdiagnosis and incorrect management of the trigeminal neuralgia (TN) patient can result in invasive dental therapies such as extensive endodontic (root canal) procedures, multiple extractions, TMJ (temporomandibular joint) surgery, etc., quite often resulting in no resolution of the patient's pain and, in many cases, making the problem worse. Topics include the onset and early development of TN, management options, dental management of the TN patient, a TN overview for patients and their families, defining TN, diagnostic methods, the causes of TN, epidemiology, and the medical and surgical treatments for TN. Drug that may be used to treat TN include carbamazepine (Tegretol), phenytoin (Dilantin), gabapentin (Neurotonin), and baclofen (Lioresal). Surgical options include radiofrequency rhizotomy (percutaneous needle used to heat the nerve and destroy the pain fibers), glycerol rhizotomy (glycerol injected to damage the pain fibers), balloon compression (used to compress the nerve and damage the pain fibers), microvascular decompression (a surgical procedure done under general anesthesia), and stereotactic radiosurgery. The article concludes with a list of the major goals and purposes of the Trigeminal Neuralgia Association (TNA). 1 figure. 23 references. •

Reduction of Severe Gingival Overgrowth in a Kidney Transplant Patient by Replacing Cyclosporin A with Tacrolimus Source: Journal of Periodontology. 71(10): 1630-1636. October 2000. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Side effects of certain drugs such as cyclosporin A (CsA) and phenytoin may induce gingival (gum) overgrowth, which in some instances becomes unacceptable to the patient because of esthetic, functional, and other effects. Use of these drugs is related to important medical situations, such as organ transplantation and control, and therefore withdrawal of the drugs is contraindicated. Tacrolimus is an immunosuppressant used to prevent graft rejection in organ transplant patients and has been shown to cause fewer oral side effects than CsA. This article describes a case of an intense gingival overgrowth in a kidney transplant patient probably because of synergism between the use of CsA and phenytoin. The treatment protocol included thorough oral hygiene, scaling and root planing, clorhexidine digluconate rinses (0.12 percent), and substituting CsA with tacrolimus. The patient's response to treatment after 6 months of tacrolimus use was excellent with almost complete reversion of the gingival enlargement. One year follow up demonstrated a stable gingival situation. The successful substitution of CsA with tacrolimus provides great expectations for the management of CsA related gingival enlargement. 2 figures. 65 references.

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Clinical Implications of Drug Interactions with the Cytochrome P-450 Enzyme System Associated with Omeprazole Source: Digestive Diseases and Sciences. 36(12): 1665-1669. December 1991. Summary: This article considers the clinical implications of drug interactions with the cytochrome P-450 enzyme system associated with omeprazole. The author reviews the in vitro, in vivo, and clinical studies designed to assess the potential of omeprazole, and presents a perspective on potential drug interactions and their clinical uses. The author concludes that, although caution should be exercised when initiating omeprazole

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therapy in patients taking concomitant diazepam, warfarin, and phenytoin, clinically significant drug interactions appear unlikely. 2 tables. 16 references. (AA-M). •

Diagnosis and Management of Sensory Neuropathies in HIV Infection Source: AIDS Clinical Care; Vol. 6, No. 2, Feb. 1994. Contact: Johns Hopkins University, Department of Neurology, Baltimore, MD, 21205. Summary: This article focuses on the two most common HIV-associated neuropathies: predominantly sensory neuropathy (PSN) or distal symmetric polyneuropathy (DSPN) and medication-induced toxic neuropathies (TN). The epidemiology, clinical features, history, physical findings, diagnosis and treatment are discussed. No large-scale, controlled-treatment trials have been conducted thus far, and therefore symptomatic treatment with pharmacologic agents is largely empiric. Choice of medication is based on the severity of the patient's symptoms and side-effect profile. When pain or other dysesthetic symptoms begin to limit functional ability, tricyclic antidepressants may be useful. Where tricyclics are not effective, second-line choices include mexiletine, carbamazepine, phenytoin, baclofen, and clonazepam. For patients with more severe neuropathic pain which inhibits walking, narcotic analgesics may be necessary. The authors present an algorithm for the management of sensory neuropathy as well as guidelines for narcotics use in patients with a history of substance abuse.

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Anaesthesia for Dental Conservation in a Patient with Tuberous Sclerosis Source: European Journal of Anaesthesiology. 13(4): 413-415. July 1996. Summary: This article presents a case report of anesthesia for dental conservation in a patient with tuberous sclerosis, complicated by epilepsy. Tuberous sclerosis is an inherited condition characterized by seizures, learning difficulties, and behavioral problems in which adenomatous lesions may occur in the skin, heart, and kidneys. The clinical onset is usually in early childhood. Phenytoin and epanutin required to control seizures can cause gingival hypertrophy, tenderness and bleeding. Routine dental examination and care is often impossible without sedation or general anesthesia. The choice of drugs was related to the patient's seizures and intercurrent therapy. Thiopentone, vecuronium, and nitrous oxide with isoflurane were satisfactory. The procedure lasted 90 minutes and included full examination, dental x-rays, scaling, filling, and extraction of teeth. The authors discuss this case and how their findings can be extrapolated to similar patients.

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Gingival Enlargements Induced By Drugs Source: Drug Safety. 15(3): 219-231. September 1996. Summary: This article reviews gingival enlargement induced by drugs. Gingival enlargement, an abnormal growth of the periodontal tissue, is mainly associated with dental plaque-related inflammation and drug therapy. Its true incidence in the general population is unknown. Gingival enlargement produces aesthetic changes, pain, gingival bleeding, and periodontal disorders. Although gingival overgrowth has been traditionally recognized as an adverse effect of phenytoin therapy, it has recently been reported in association with the use of cyclosporin and calcium antagonists. These three classes of drugs produce important changes in fibroblast function, which induce an increase in the extracellular matrix of the gingival connective tissue. In the majority of those patients for whom dosage reduction, or drug discontinuation or substitution is not possible, and for whom prophylactic measures have failed, surgical excision of gingival

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tissue remains the only treatment of choice. However, oral hygiene, periodontal prophylaxis, and careful control of dental plaque could reduce the incidence of druginduced gingival enlargement, especially when instituted at or near the beginning of drug treatment. 5 figures. 152 references. (AA-M). •

Taking the Cure Source: Digestive Health and Nutrition. p. 18-20, 32. September-October 2000. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: This article reviews the symptoms of common digestive disorders and the medications used to treat them. The author first considers heartburn, indigestion, and sour stomach, noting that both antacids and acid reducers (also known as H2 blockers or H2 antagonists) relieve these conditions by reducing the acidity level in the stomach. However, antacids only work on the gastric acid already released into the stomach. Acid reducers, on the other hand, reduce the amount of stomach acid produced. Over the counter (OTC) antacids neutralize the acid in the stomach, but can also cause problems for some people, including those with poorly functioning kidneys or those on antibiotics. People taking theophylline (an oral asthma drug), warfarin (for blood thinning), or phenytoin (anti-seizure medication) should avoid Tagamet HB, which contains cimetidine. The section concludes with a list of common antacids and acid reducers and their generic drug names. For excessive gas, products that contain simethicone, a defoaming agent, are said to break up gas bubbles and make them easier to eliminate from the body. Other productions, such as Beano, contain an enzyme that reduces gas production in some people; activated charcoal tablets also absorb gas. For people who lack the enzyme lactase (needed to digest milk sugar, or lactose), lactase drops and tables are available. Few OTC medications are available to help nausea. Constipation can be a very real problem, but is also over perceived in many people; the author stresses that daily bowel movements are not necessarily required. Laxatives should be used only occasionally; if overused, they can make the intestine become insensitive and the patient may lose the natural urge to have a bowel movement. For diarrhea, it is important to guard against dehydration (the loss of water and electrolytes). And, finally, a number of OTC medications, in forms ranging from suppositories and creams to pads and foams, are available to help with the symptoms of hemorrhoids.

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Prescription and Over-the-Counter Drugs: The Ins and Outs Source: Diabetes Forecast. 45(2): 36-39. February 1992. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article summarizes drug reactions and interactions, focusing on problems commonly encountered by people with diabetes. The authors focus on the major drugs known to affect diabetes control. Three sections discuss over-the-counter and recreational drugs, including alcohol, aspirin, caffeine, cold remedies and diet pills, marijuana, sugary medicines, and tobacco; drugs that increase blood glucose levels, including corticosteroids, diazoxide, diuretics, epinephrine and adrenaline, estrogens, lithium carbonate, nicotinic acid and niacin, phenobarbitol, phenytoin, propanolol, rifampin, and thyroid preparations; and drugs that decrease blood glucose levels, including anabolic steroids, chloramphenicol, coumarin anticoagulants, fenfluramine,

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methyldopa, monoamine oxidase inhibitors, phenylbutazone, propanolol, and sulfa drugs. The authors conclude by encouraging readers to educate themselves about all drugs and medicines they are taking. •

Suspected Kidney Disease: Putting Urinalysis Clues into Context, Part 2 Source: Consultant. 41(12): 1829-1830, 1833-1834, 1836. December 2001. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article, the second in a series on diagnosing suspected kidney disease, explains how urinalysis clues may be used to help the diagnosis. In evaluating a patient with acute oliguria (lack of urination), the physician must first determine whether the cause is postrenal, prerenal, or renal (kidney). Ultrasonography can rule out obstruction; minimal or no proteinuria (protein present in the urine) excludes glomerular (the filtering units of the kidney) involvement. Acute interstitial nephritis (AIN) may be present in a patient who has the classic triad of acute renal failure, fever, and rash. Drugs that can cause AIN include penicillins, cephalosporins, NSAIDs (nonsteroidal antiinflammatory drugs), diuretics, H2 blocking agents, phenytoin, phenobarbital, and allopurinol; NSAIDs are the most common culprits. In patients with AIN, urinalysis may show microscopic hematuria (blood in the urine), white blood cell casts (sterile pyuria), non nephrotic range proteinuria, or eosinophils. However, eosinophiluria can occur in other inflammatory processes, including prostatitis, cystitis, pyelonephritis, cholesterol emboli, and, on occasion, rapidly progressive glomerulonephritis. In patients with nephrolithiasis (kidney stones), crystals in the urine suggest the predominant stone composition, which can be confirmed by stone opacity (assessed by x ray), urine pH, family history, and stone anatomy. The authors use three case studies to illustrate these concepts. 7 figures. 1 table. 6 references.

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Pyogenic Granuloma in a Renal Transplant Patient: Case Report Source: SCD. Special Care in Dentistry. 21(5): 187-190. September-October 2001. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Summary: This case report describes a 14 year old female referred to Pediatric Dentistry for evaluation and treatment of cyclosporine-induced gingival hyperplasia (overgrowth of the gum tissue due to the drug cyclosporine, an immunosuppressant). Examination of the anterior maxillary (upper jaw) area showed a red, vascular, exophytic, soft tissue mass which had been excised a few months earlier without a histopathological examination being done. The mass did not appear consistent with gingival overgrowth induced by long term use of medication, and thus an excisional biopsy was performed. The results of the biopsy allowed diagnosis of the lesion as a pyogenic granuloma. The authors review the literature and discuss management recommendations for this type of patient. The authors conclude by reminding dental practitioners that in patients who take medications which can induce gingival overgrowth (e.g., cyclosporine, phenytoin, nifedipine), a biopsy is indicated for all gingival lesions. 4 figures. 20 references.

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Management of Localized Scleroderma Source: Seminars in Cutaneous Medicine and Surgery. 17(1): 34-40. March 1998. Summary: This journal article provides health professionals with information on the pathogenesis and treatment of localized scleroderma, which denotes a spectrum of

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conditions characterized by circumscribed fibrotic areas involving different levels of the dermis, subcutis, and sometimes underlying soft tissue and bone. Different clinical manifestations of localized scleroderma exist. From a therapeutic viewpoint, a subdivision that includes the extent and level of fibrosis in the skin, resulting in plaque, generalized, linear, and deep type, is helpful in choosing the appropriate therapy and determining its effectiveness. Although the pathogenesis of the different types of localized scleroderma is unknown, the pathological conditions observed in patients who have it affect mainly the connective tissue; however, this is associated with alterations of the immunologic system and the vessel walls. Although the clinical course of the disease is often benign, widespread lesions and disabling joint contractures may lead to significant complications. Numerous therapeutic agents have been reported to be effective in this disease spectrum; they include topical steroid creams; oral medications such as vitamins E and D3, phenytoin, retinoids, antibiotics, griseofulvin, interferon gamma, and oral steroids; ultraviolet A (UVA) irradiation and psoralen UVA therapy; physical therapy; and surgery. 2 figures, 2 tables, and 54 references. (AA-M). •

Porphyria Cutanea Tarda: Don't Forget To Look at the Urine Source: Postgraduate Medicine. 105(4): 208-210,213-214. April 1999. Summary: This journal article uses a case report to provide health professionals with information on porphyria cutanea tarda. A 40 year old man presented to his primary care physician with painful blisters on the backs of his hands. The man, who was a landscaper, reported that the blisters had erupted shortly after the landscaping season began. His only significant medical history was a partial complex seizure disorder that had begun about 3 years earlier after a head injury. He had been taking phenytoin since then. His weekly alcohol consumption was about eighteen 12-ounce cans of beer. The presumptive diagnosis was porphyria cutanea tarda. Although cultures obtained from intact bulla failed to grow organisms, a 24-hour urine collection showed significantly elevated carboxyporphyrin levels. The patient was advised to apply sunscreen with a high sun protection factor, cover exposed skin with clothing, find an indoor occupation, and abstain from drinking alcohol. Porphyrias result from inherited or acquired deficiencies in any one of several enzymes that synthesize heme. When a given enzyme is absent or in short supply, porphyrins are shunted away from heme synthesis into pathways that produce porphyrin by-products, that build up in tissues and cause the clinical manifestations of porphyria. Diagnosis of porphyria cutanea tarda is usually fairly straightforward because of the characteristic clinical findings such as urine that is red to brown in natural light and pink to red in fluorescent light. Once the diagnosis is confirmed, it appears reasonable to screen all patients with porphyria cutanea tarda for hepatitis C and possibly B. Therapeutic measures include avoiding exacerbating factors, undergoing phlebotomy, or using chloroquine therapy. 3 figures, 1 table, and 9 references. (AA-M).

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Treatment of Common GI Disorders in the Elderly Source: Drug Therapy. 21(1): 23-24, 31-34, 39. January 1991. Summary: This review article focuses on the pharmacologic treatment of selected gastrointestinal (GI) diseases common in the aged. Diseases discussed include gastroesophageal reflux, including symptoms, nonpharmacologic treatment, and the use of prokinetic agents; gastric ulcer, notably the use of antacids and H2-receptor antagonists and their side effects; and inflammatory bowel disease, both Crohn's disease and ulcerative colitis. Drugs covered include 4-aminosalicylic acid and 5-aminosalicylic acid, azathioprine, bethanechol, cimetidine, cisapride, cyclosporine A, domperidone,

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Phenytoin

famotidine, lidocaine, magaldrate, 6-mercaptopurine, methotrexate, metoclopramide, misoprostol, nizatidine, olsalazine, omeprazole, phenytoin, procainamide, ranitidine, sucralfate, sulfasalazine, theophylline, and warfarin. 4 tables. 53 references.

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

Project Title: CHEMOPREVENTIVE AGENTS AND HUMAN CYTOCHROME P450 IN VIVO Principal Investigator & Institution: Wilkinson, Grant R.; Professor of Pharmacology; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: The development of cancer frequently involves an environmental component(s) and for this reason a prevention strategy is a particularly attractive approach for reducing cancer risk. To this end, various putative chemopreventive agents are either under preclinical investigation, development as drugs, or clinical evaluation. The rationale of certain of these agents is based on the notion that most environmental (pro)carcinogens are inactive per se and require metabolic activation, and that the balance between this process and subsequent elimination is important in an individual's susceptibility to the cancer process. Accordingly, decreasing an appropriate Phase I activating enzyme and/or increasing an important Phase II detoxifying enzyme could reduce cancer risk. However, because such modulation is not likely to be limited to a single enzyme or system, the selectivity of the interaction may be less than previously thought or desired. The cytochrome P450 (CYP) system is particularly important in this regard because it is often critical in procarcinogen activation, and these enzymes are also very important in the metabolism of drugs. Accordingly, the administration of a chemopreventive agent may not only alter cancer risk but also drug efficacy. The goal of the proposed research, therefore, is to determine the effects of selected chemopreventive agents on the in vivo activity of specific CYP enzymes in healthy human subjects. The agents to be studied are oltipraz, phenethylisothiocyanate and S-allylcysteine, which have either just become, or are about to be available for clinical investigation. The

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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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proposed experimental approach will be based on a conventional drug interaction study design using selected in vivo probes, reflective of the activity of individual CYP isoforms, in order to determine the inhibitory and/or inductive effects of single and repeated doses of the chemopreventive agent on the probes metabolism. The CYP isoforms of interest and the associated in vivo probes will be CYP1A2 (caffeine), CYP2A6 (coumarin), CYP2C9 (tolbutamide), CYP2C19 (mephenytoin), CYP2D6 (debrisoquine), CYP2E1(chlorzoxazone) and CYP3A(midazolam). The resulting data will provide, for the first time, information about such interactions in vivo in humans the ultimate model -rather than in animals and/or in in vitro preparations. Moreover, the information will be of value in the further development and evaluation of the efficacy/ toxicity of these new chemopreventive agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORTICAL PLASTICITY: MECHANISMS AND MODULATION Principal Investigator & Institution: Hodge, Charles J.; Neurosurgery; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Stroke and traumatic brain injury afflict more than 600,000 Americans annually, resulting in some level of functional impairment. While stroke afflicts primarily an adult population, traumatic brain injury affects mostly children and young adults. Variable recovery of function and some dysfunction will occur in most patients due to the innate ability of the nervous system to reorganize. This process is known as plasticity. Recent studies demonstrate a dramatic improvement in the speed and extent of behavioral recovery after brain injury by the use of the neurostimulant amphetamine. In contrast, phenytoin, a commonly administered antiseizure medication, retards recovery. Although the effects of these drugs have been demonstrated on behavioral recovery in both animal models and humans, their influence on mechanisms of plasticity remains largely unknown. The purpose of this project is to determine mechanisms that govern plasticity in a well-characterized rat model of cortical injury that results in a well-defined plastic response observed through functional optical imaging techniques. We propose to: * Evaluate the modulation by damphetamine (stimulant) and phenytoin (depressant) on functional cortical reorganization in the rat whisker/barrel cortex following a focal excitotoxic injury, utilizing intrinsic optical imaging. * Examine changes in gene expression that are associated with plasticity using "gene chip" techniques in individual affected and spared cortical barrels to decipher the genetic response underlying observed functional outcomes and to gain insight into mechanisms by which d-amphetamine alters recovery following injury. * Determine whether structural alterations in the intra-cortical or thalamocortical connectivity correspond to observed functional changes using neural pathway tracing techniques. Functional imaging techniques allow us to determine the extent and time course of plastic changes in a longitudinal fashion. Our studies will elaborate critical aspects of cortical plasticity in terms of underlying gene expression, structural and functional reorganization following focal cortical injury. The determined responses will be modulated by pharmacologic agents in common clinical usage. The insight gained from these studies will help determine most effective management of patients to maximize recovery from brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYP2C9--ACTIVE SITE STRUCTURE--MOLECULAR MODELING ASPECTS Principal Investigator & Institution: Trager, William F.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term aim of the research described in this proposal is to understand the structural basis underlying the unique substrate specificities of the human CYP2C proteins. This is important for the avoidance of inhibitory drug-drug interactions involving this important P450 sub-family, and in particular CYP2C9, during the development of new therapeutic agents. Our preliminary data derived from CoMFA modeling, homology modeling and site-directed mutagenesis studies, suggest that the binding of coumarin anticoagulants and anticonvulsant hydantoins to CYP2C9 is governed by an aromatic binding interaction within the B'-helix, and two electrostatic interactions (E1 and E2) within elements of the F, G and I-helices of the enzyme. The primary goal of this research is to test this hypothesis in order to refine our active-site model for CYP2C9. CYP2C19, which share greater than 90% sequence homology with CYP2C9, also metabolizes the coumarins and hydantoins but generates metabolite profiles quite distinct from CYP2C9. Therefore, the active-sites of CYP2C9 and CYP2C19 likely share some common binding determinants which should facilitate the related goal of developing a three-dimensional active-site model for CYP2C19. The Specific Aims of this proposal are; 1. Construction of new CoMFA models for CYP2C9 and CYP2C19 based on Ki values for the inhibition of both isoforms by Type I and Type II ligands. 2. Identification of active-sites residues in CYP2C9 and CYP2C19 through photo-affinity labeling and analysis of adducted residues by electrospray and MALDI mass spectrometry. 3. Identification of electrophilic binding site determinants in CYP2C9 through the construction of hybrid CYP2C9/CYP2C19 proteins and point mutants, and analysis of their interaction with valproic acid, phenytoin and phenprocoumon. This three-tiered approach involves the use of complementary techniques which will permit the iterative refinement of three-dimensional structural representations of CYP2C9 and CYP2C19. This approach provides a powerful internal control for the procedures which we are using, by ensuring that discrete CYP2C9 and CYP2C19 structural representations are created rather than a low resolution "global" CYP2C model. Finally, if we can develop discrete models for the closely related CYP2C9 and CYP2C19 isoforms, there should be little impediment to the future generation of active-site models for the other human CYP2C isoforms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EARLY RANDOMIZED SURGICAL EPILEPSY TRIAL Principal Investigator & Institution: Engel, Jerome J.; Professor; Neurology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2008 Summary: (provided by applicant): This grant application for an early randomized surgical epilepsy trial (ERSET) was originally prepared with the help of planning grant R21 NS37897, awarded in recognition of the fact that mesial temporal lobe epilepsy (MTLE) is a surgically remediable syndrome, that surgical treatment for this disorder is underutilized, and that true equipoise exists concerning the relative benefits of surgery vs. continued treatment with new antiepileptic drugs, early in the course of the disorder. We now submit a revised proposal for a multicenter randomized controlled trial (RCT) to compare the efficacy of early surgical intervention for MTLE with continued optimal

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pharmacotherapy. The primary outcome measure will be freedom from disabling epileptic seizures (complex partial and secondarily generalized seizures, and simple partial seizures that are apparent to an observer). Patients aged 12 years and older with suspected MTLE will be candidates for recruitment if disabling seizures: 1) have not responded to two or more antiepileptic drugs, one of which must be either Dilantin, Tegretol, or Carbatrol, and 2) have not persisted, according to defined criteria, for more than two years. Fifteen epilepsy surgery centers spaced evenly across the country will actively recruit patients meeting these criteria. These patients will undergo a rigid presurgical evaluation protocol, standardized across centers, and 200 surgical candidates will then be randomized to either anteromesial temporal resection or two years of additional pharmacotherapy. Studies will test five hypotheses: 1) Surgical treatment will be more effective than medical treatment in reducingthe frequency and severity of epileptic seizures; 2) Surgical treatment will be more effective than medical treatment in improving quality of life; 3) Surgical treatment will be more effective than medical treatment in improving psychological and social function; 4) Morbidity and mortality associated with surgical treatment will be no greater than that associated with medical treatment; and 5) Progressive hippocampal atrophy and mesial temporal hypometabolism will occur only in patients who continue to have frequent complex partial and generalized tonic-clonic seizures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF AGE ON GLUCURONIDATION OF ANTIEPILEPTIC DRUGS Principal Investigator & Institution: Remmel, Rory P.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: The pharmacokinetics and metabolism of antiepileptic drugs (AEDs) in the eldedy population is poorly studied, particularly in the old and old-old (patients >-75), that comprise the fastest growing population group in the U.S. Glucuronidation is a major metabolic pathway for several AEDs including lamotrigine, oxcarbazepine, and valproic acid. In this project, the pharmacokinetics of lamotrigine and valproic acid will be studied in younger adults (ages 18-50) and elderly patients (ages 65-74 and >-75) by a novel stableisotope technique. An innovative formulation of stable-labeled isotope of lamotrigine will be prepared in solutions of 2-hydroxypropyl-beta-cyclodextrin in water. Studies on the glucuronidation of this drug as well as valproic acid, the major oxidative metabolite of phenytoin, p-HPPH and the active form of oxcarbazepine, 10hydroxy carbamazepine, will be conducted with a pre-existing human liver microsomal tissue bank that has been obtained from elderly donors. The individual glucuronosyltransferase enzymes responsible for the glucuronidation of these AEDs and metabolites will be identified by kinetic studies in microsomes and screening with cloned, expressed enzymes. These studies will be done to help predict drug interactions that may occur between AEDs and between AEDs and other drugs that are glucuronidated. Individual drug interactions will be studied in vitro in microsomes prepared from elderly donors. The goal of this project is to determine if AED glucuronidation is affected by age and to develop dosing guidelines for the major elderly age groups: the young-old, the old, and the old-old. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPILEPSY CLINICAL RESEARCH PROGRAM Principal Investigator & Institution: Leppik, Ilo E.; Professor; Neurology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUL-1980; Project End 31-AUG-2007 Summary: (provided by applicant): The incidence of epilepsy rises rapidly after age 60 with a reported prevalence of 1.48% for persons over 75. Pharmacoepidemiologic studies performed during the current P50 show that the prevalence of anti epileptic drug (AED) use is approximately 2% among the community-dwelling elderly (Health Care Finance Administration data set (n = ~12,000/yr) and approximately 9% among nursing home residents (Beverly data set). Clearly, the absolute number of elderly using AEDs will increase greatly in the near future, but very little is known about the safe and effective use of these powerful modulators of neurological functioning in this population. The goal of this 5-year program project is to increase our knowledge of the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacoepidemiology (PE) of AEDs in the elderly. This information is critical for the design of appropriate controlled trials and the development of evidence-based guidelines for this population. We will investigate these issues using a variety of approaches including hepatic microsomes in vitro liver, stable labeled isotopes in volunteers, non-linear mixed effect modeling (NOME) and application of estimated AED concentrations to outcomes in a large nursing home population. Extensive genotyping of CYP3A4/5 and initial investigation of genetic and racial factors in AED metabolism will be carried out. The PK characteristics of carbamazepine (CBZ), valproic acid (VPA), lamotrigine (LTG), and topiramate (TPM) in elderly patients will be determined using stable labeled intravenous preparations developed by our group. NONMEM analysis will be performed using clinical data from Minnesota, Atlanta, Miami, and the national Veterans Administration Cooperative Study. These 3 sites will provide the largest group of elderly persons with epilepsy ever studied and have enough power to test the hypotheses. Findings regarding phenytoin (PHT), CBZ and VPA PK from the current and proposed P50 will be applied to dose, weight, and to outcome measures in the extant Beverly Nursing Home database. This will allow us to estimate AED concentrations in this population and determine prevalence and type of adverse events associated with high, middle, or low concentrations. The information obtained from this multi-pronged effort will have profound impact on the use of AEDs in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FOLATE AND OTHER COFACTORS IN THE METABOLISM OF PHENYTOIN IN PREGNANT WOMEN Principal Investigator & Institution: Van Dyke, Don C.; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: The goal of this study is to evaluate the effect of phenytoin and carbamazepine on folate, zinc, vitamin B12 and urinary biotin during pregnancy and at various intervals postpartum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GROWTH FACTORS AND GINGIVAL FIBROSIS Principal Investigator & Institution: Trackman, Philip C.; Periodontology & Oral Biology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118

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Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 30-JUN-2007 Summary: (provided by applicant): The clinical condition of gingival overgrowth consists of excess gingival tissues that creates disturbances in the oral environment and creates related systemic complications. For example, impaired mastication and impaired oral hygiene can result, respectively, in poor nutrition and increased microbial load in the oral cavity. There are two principal classifications of gingival overgrowth. Druginduced gingival overgrowth is a side effect resulting from therapy with certain pharmacologic agents. Hereditary gingival fibromatosis is unrelated to pharmacological therapies. Recent studies from our laboratory show that phenytoin-induced gingival overgrowth lesions are fibrotic and contain elevated levels of connective tissue growth factor (CTGF), whereas nifedipine- and cyclosporin A-induced lesions are less fibrotic and have low levels of CTGF, and non-overgrowth tissues have no detectable CTGF. Our in vitro studies show that CTGF stimulates insoluble collagen accumulation in cultured human gingival fibroblasts. Fibrosis and CTGF levels have been associated in other pathologies. The molecular and cellular activities stimulated by CTGF that promote fibrosis are not well understood. The goals of the current proposal are (1) to identify functional domain(s) of CTGF that stimulate insoluble collagen accumulation, proliferation and apoptosis by cultured human gingival fibroblasts utilizing a series of domain-specific monoclonal CTGF antibodies; (2) determine mechanisms by which phenytoin increases CTGF itself in cultured human gingival fibroblasts focusing on prostaglandin and CAMP metabolism, and on phenytoin modulation of signal transduction pathways related to TGF-beta stimulated CTGF transcription (3) assay human drug-induced gingival overgrowth tissues and hereditary human gingival overgrowth tissues for the presence of markers related to the novel molecular mechanisms explored in vitro: prostaglandin receptors, proliferation markers, and markers for apoptosis. This experimental approach that utilizes bioassays of human gingival fibroblasts in vitro, and human gingival overgrowth tissues samples is expected to identify biologically active domains of CTGF, and mechanisms by which CTGF promotes gingival fibrosis. In addition, these findings will likely have relevance to fibrotic pathologies that occur in other tissues that also contain elevated levels of CTGF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN CYP2C MODELS Principal Investigator & Institution: Rettie, Allan E.; Professor and Chair; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The long-term aim of this research is to understand the structural basis underlying the unique substrate specificities of the human CYP2C enzymes. Enzyme inhibition during polytherapy, particularly for CYP2C9, is a general mechanism underlying severe drug-drug interactions with agents such as warfarin and phenytoin. Adverse drug reactions of this type are a major, but potentially avoidable, drain on health care costs in the US. However, our ability to predict inhibitory drug-drug interactions from data obtained in vitro is limited by the lack of high resolution structures and robust pharmacophore models for these P450 enzymes, as well by complications imposed by the observation of atypical Michaelis-Menten kinetics and Type II inhibitor complex formation. This project addresses these limitations with the following specific aims: Specific Aim 1: Construct new CYP2C CoMFA models by determining the inhibition constants for a series of benzbromarone analogs to determine which features confer strong binding interactions with CYP2C9, CYP2C19 and CYP2C8. Specific Aim 2: Determine the effect of pKa and steric factors on strength of type II

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interactions by measuring binding affinities to CYP2C9 for a series of coumarin-based ligand molecules with and without nitrogen-bearing substituents and with different steric features adjacent to the nitrogen. Specific Aim 3: (a) Determine the structural basis for homotropic cooperative behavior of phenacetin (and pyrene) with human CYP2C9 and CYP2C19 through site-directed mutagenesis, (b) develop complementary NMR approaches to the study of human CYP2C cooperativity. Specific Aim 4: (a) Delineate the role of Arg108 in CYP2C9 substrate selectivity; (b) engineer a soluble, monomeric form of the ultra-stable, iron-nitrogen coordinated Arg108His mutant, and (c) develop histidine scanning mutagenesis and formation of the iron-nitrogen complex as a tool for examining the role of CYP2C9 B-C and F-G loop region mobility in substrate specificity. In this manner, we will bring together organic synthesis, QSAR analysis of Type I and Type II ligands, site-directed mutagenesis, conformational analysis of protein flexibility and, ultimately, crystallography of human CYP2C mutants, to develop an integrated picture of ligand interactions with these important human enzymes that will enable us to assess, in a prospective manner, the potential for inhibitory drug-drug interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING PATIENT SAFETY BY REDUCING MEDICATION ERRORS Principal Investigator & Institution: Strom, Brian L.; Professor of Medicine and Pharmacology; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 07-SEP-2001; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT) Medication errors are among the most common and potentially preventable types of medical errors, accounting for more deaths than motor vehicle accidents, breast cancer, or HIV, and an annual cost of $17 to 29 billion. The elderly are particularly at risk for such complications. The highest risk drugs include anticoagulants, anticonvulsants, antimicrobials, and digoxin. The most frequent serious adverse outcomes include bleeding and acute renal failure. Medication errors can occur anywhere in the medication use process, including diagnosis, prescribing, dispensing, administering, ingesting, and monitoring. Sources of medication errors are quite varied. Among health care professionals, factors such as work stress, distractions, interruptions, inadequate training, fragmented information, or information overload may increase the risk of committing errors, such as prescribing the wrong drug or dose, or omitting needed action in the course of delivery of care, such as failing to properly monitor the use of nephrotoxic drugs or anticoagulants. Among patients, factors such as advanced age, frailty, cultural or literacy barriers, mental illness or incapacity, or lack of adequate social support may contribute to poor adherence with a specified therapeutic regimen. Poor adherence accounts for almost a quarter of all hospital admissions attributed to drugs, and can take the form of overuse, underuse, or erratic use of the drug. Building on its 20 years of experience studying adverse drug reactions and other medication safety problems, the University of Pennsylvania proposes a Center of Excellence for Patient Safety Research and Practice. The proposed Center will re-focus this large past experience on the expansion of this patient safety knowledge base through multidisciplinary research and education programs that are designed to identify and implement systems approaches to reducing error in the use of medications. In particular, we propose a program that will combine investigators in pharmacoepidemiology, health services research, biostatistics, occupational medicine, sociology, psychology, and economics to address a theme of "Improving Patient Safety Through Reduction of Errors in the Medication Use Process." The program will be

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composed of four projects and four cores, based at the University of Pennsylvania and linked to the government of the State of Pennsylvania and to the network of Centers for Education and Research in Therapeutics. Each of the four cores will serve the four projects, in such a way as to maximize quality and efficiency simultaneously. Project 1 will study patient and system factors that are predictive of hospitalizations due to doserelated medication errors among elderly individuals taking specific high-risk drugs (warfarin, phenytoin, and digoxin), using a State-run population-based pharmaceutical benefit program. Project 2 will study human and medical practice factors as predictors of poor adherence to warfarin therapy in an anticoagulation clinic setting created as a systems approach to prevent medication errors. Project 3 will study medication errors as causes of preventable acute renal failure in the inpatient setting, despite the existence of a pharmacokinetic monitoring service created to prevent such problems. Project 4 will study conditions that lead to medication errors among physicians, with emphasis on work conditions that increase stress, such as workload, schedules, work organization, shifts, and patient/staff ratios. Core A will be an administrative core, responsible for coordination. Core B will be a data collection core, responsible for all field activities. Core C will be a biostatistics and data management core, responsible for data entry, management, and analysis. Core D will be a dissemination core, responsible for an extensive dissemination program, as the results of the program emerge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITORY AND INDUCING EFFECTS OF HERBAL MEDICINES ON CYP ENZYMES Principal Investigator & Institution: Edeki, Timi I.; Associate Professor; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-JUL-2006 Summary: (provided by applicant): In recent years there has been an increased consumption of herbal medicines. Most of those that take these medicines also consume other conventional medicines, and do not inform their physicians about the use of herbal medicines and other alternate medical practice. In addition, most of these herbal medicines have not been rigorously studied and have not been subjected to the same standards as conventional medicines. As a result of this, there is a dearth of information on possible interactions between herbal products and drugs. Contrary to the opinion of most consumers that these herbal products are benign, a number of interactions have recently been reported between herbal medicines and conventional drugs. This increased use of herbal medicines exposes a significant percentage of the population to unknown herb drug interactions. Our hypotheses are that the metabolism of drugs mediated by cytochrome P450 (CYP) enzymes, can be modulated by ingestion of herbal medicines such as ginseng, ginkgo biloba and St. John's wart, and that ethnicity is a factor in this modulation. The resulting induction or inhibition will therefore affect the metabolism of the drugs that are substrates of these enzymes. Since many clinically important drugs are CYP substrates, there are implications for herb-drug interactions. In light of the above, the specific aims of this grant proposal are the realization of the following objectives: 1) To determine if the active pharmaceutical ingredients of American ginseng, Korean ginseng, gingko biloba and St. John's wart inhibit CYP2C9, CYP2C19, CYP2D6, and CYP3A4 activities, with tolbutamide, mephenytoin, bufuralol and testosterone as an in vitro probes, using microsomes prepared from human liver. 2) To determine if genotype is a factor on these inhibitory effects. 3) To determine the inducing or inhibiting effects of the important components of St. John's wart, American ginseng, Korean ginseng and gingko biloba on CYP2C9, CYP2C 19, CYP2D6, CYP3A

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activities in human hepatocytes obtained from Caucasians and African Americans. 4) To determine if there are interethnic differences between African Americans and Caucasians in the possible CYP enzymes modulating effects of herbal medicines in human hepatocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LAMOTRIGINE IN TREATMENT OF PAINFUL HIV ASSOCIATED SENSORY NEUROPATHY Principal Investigator & Institution: Mcarthur, Justin C.; Professor of Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: This is a phase II, multicenter, randomized, double-blind, placebo- controlled trial of the safety, tolerability and efficacy of pain relief of lamotrigine for HIVassociated sensory neuropathy. Peripheral neuropathy is a common complication of HIV infection. HIV-associated sensory neuropathy is a common form of neuropathy in advanced HIV infection. Approximately 30% of patients with AIDS develop HIVassociated sensory neuropathy. Symptoms can be painful and can greatly impact on the activities of daily living as well as the quality of life. A direct viral etiology has been postulated as a causative agent. Certain antiretrovirals (ddI, ddC, d4T) are also known to cause neuropathy in this patient population. Therapeutic treatment of painful sensory neuropathy has been difficult. Current management involves the use of sympomatic or pain-modifying agents. Symptomatic relief with tricyclic antidepressants, non-steroidal anti-inflammatory agents, topical capsaicin or opiates has been limited. A trial is currently underway with a potentially restorative agent, nerve growth factor. Lamotrigine is a newly approved anti-convulsant which blocks voltage sensitive sodium channels, resulting in inhibition of glutamate and aspartate release. Lamotrigine has similar efficacy in maximal electro- shock models to carbamazepine and phenytoin, both of which have proven efficacious for the treatment of painful diabetic neuropathy. To date, there have only been anectodal reports of the efficacy of lamotrigine for treatment of HIV-associated sensory neuropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS INTERACTIONS

OF

ATYPICAL

DRUG

KINETICS

AND

Principal Investigator & Institution: Tracy, Timothy S.; Basic Pharmaceutical Sciences; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2003 Summary: (Adapted from the Applicant's Abstract): Toxicological consequences may occur when drug interactions involve drugs with narrow therapeutic indices such as the cytocbrome P450 2C9 (CYP2C9) substrates warfarin and phenytoin. To minimize risk to humans, accurate predictions of in vivo drug metabolism, pharmacokinetics and drug interactions from in vitro data are needed. Recently, careful examination of drug metabolism kinetic data has demonstrated that atypical kinetics of cytochrome P450 mediated reactions may occur with greater frequency than previously believed. Atypical kinetic profiles such as autoactivation, activation and substrate inhibition have been observed for several P450 isoforms including CYP2C9. These atypical kinetic processes may be either homotropic (involving only one substrate) or heterotropic (involving a substrate and another effector/substrate). Since these kinetic patterns are observed in vitro and investigators use these in vitro data to predict in vivo pharmacokinetics, it is

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imperative that the mechanisms for these interactions be studied to form a better foundation for in vitro-in vivo predictions of human drug metabolism and drug interactions. We hypothesize that critical amino acid changes in the CYP2C9 enzyme can alter the degree of cooperativity observed, that key molecule structural characteristics are required for heterotropic cooperativity, that these cooperativity interactions can be modeled and cooperativity can be observed in vivo. Using expressed CYP2C9 allelic variants and site-directed mutagenesis, metabolism of CYP2C9 substrates, which exhibit various kinetic profiles, and their interactions with a known effector (and a series of structural analogs) will be studied and modeled. Additionally, in vivo studies of a CYP2C9 substrate and a known (in vitro) effector will be conducted. Taken together, these results will improve CYP2C9 in vitro-in vivo predictive capabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDICATION ERRORS LEADING TO HOSPITALIZATION OF THE AGED Principal Investigator & Institution: Metlay, Joshua P.; Assistant Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: (PROVIDED BY APPLICANT) Medication errors leading to adverse events are a major cause of preventable hospitalizations, particularly among the elderly. Medication errors that result in dose-related adverse events can occur anywhere along the medication use process. The specific causes of and solutions for medication errors are likely to differ across drugs with different properties. Thus, investigations of errors must focus on specific drugs, particularly those with a narrow therapeutic index, such as warfarin, phenytoin, and digoxin. Error prevention strategies might include programs that improve therapeutic drug dosing and monitoring (phenytoin), improve patient drug adherence (warfarin), or reduce physician gaps in knowledge about the risks and benefits of drugs (digoxin). However, the precise design of interventions requires information on the underlying causes of these errors for both new and chronic users of these specific agents. Moreover, such interventions will only be feasible if they can be targeted to high-risk groups of patients for whom the absolute risk of adverse events due to medication errors is sufficiently high to justify these interventions. The primary aim of this project is to identify predisposing factors for hospitalizations due to errors in medication use among a large, representative cohort of community-dwelling elderly patients initiated or maintained on warfarin, phenytoin, and digoxin. The primary study hypothesis is that uncoordinated medical and pharmaceutical care, inadequate delivery of new medication instructions, visual and cognitive impairment, and psychosocial barriers (depression, coping, and support) are predisposing factors for medication errors resulting in hospitalization. The secondary aims of this study are (1) to develop a prediction rule to identify elderly outpatients at high risk for hospitalization due to errors in use of these drugs, and (2) to estimate the costs associated with hospitalization due to these errors. The hypotheses for these aims are: (1) patient factors can be used to accurately predict groups at high risk for these hospitalizations, and (2) the costs of these errors outweigh the costs of potential targeted interventions. The proposed study is a prospective cohort study enrolling members of the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE). Subjects will be sampled across the State to ensure geographic diversity in the study sample. At the time of enrollment in the cohort, subjects will undergo a detailed baseline interview to identify key psychosocial, behavioral, and clinical predictors. Outcomes will be identified over a two-year follow-up period by regular phone contact with cohort

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members using a screening instrument to identify hospitalizations. Medical records will be reviewed, and clinical findings, along with admission drug or anticoagulation levels, will be used to identify hospitalizations that are likely due to medication errors. Analyses will focus on the identification of risk factors and development of a prediction rule to identify subjects at high risk of hospitalization due to medication errors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORING CLINICAL INVESTIGATORS IN SCHIZOPHRENIA Principal Investigator & Institution: Malaspina, Dolores; Professor; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 18-AUG-2000; Project End 31-JUL-2005 Summary: This is an application for a Mid-Career Investigator in Patient-Oriented Research at Columbia University Department of Psychiatry. The candidate is an Associate Professor who completed residency training in 1987 followed by a Clinical Research Fellowship in 1989. Since then, she has had independent and continuous research support from both federal and private sources, which are expected to continue throughout the award period. The objective of Columbia University is to secure the candidate's time for mentoring beginning clinical investigators, including psychiatric residents, post-doctoral fellows, medical students, and nursing and for using her exceptional skills as a translator of science across disciplines and the clinical interface. Based upon this application, the candidate would become: training director for the Columbia NIMH Post-doctoral Schizophrenia Research Fellowship, coordinator of the PSY-1 psychiatric residency's research program, and the co-director of the Columbia Stanley Research Scholarship program for medical students. She would also provide research training for clinical psychology students and psychiatric nurses. The setting for her research and planned activities for this award is in the Columbia NIMH developing schizophrenia research center. The candidate's research proposals examine genetic and environmental etiologies of the schizophrenia syndrome, psychobiology of schizophrenia, and treatment response and determining prognostic variables of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MULTIPLE TRANSMISSION

CLASSES

OF

CA2+

CHANNELS

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SENSORY

Principal Investigator & Institution: Todorovic, Slobodan M.; Anesthesiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 16-AUG-2000; Project End 31-JUL-2005 Summary: This is an application for a K award (Research Career Development Award) from NIDA. The applicant is an anesthesiologist who is interested in studying the role of Ca2+ channels in sensory transmission including nociception with the long term goal being to determine the potential of Ca2+ channel blockers for better management of chronic pain. The applicant has chosen for his primary sponsor Charles F. Zorumski, M.D., a psychiatrist and neuroscientist who is a leader in the fields of glutamate research and CNS synaptic physiology. He will be co-sponsored by Christopher J. Lingle, Ph.D., an established neuroscientist and biophysicist who is pursuing research studies of Ca2+ channels that are relevant to the applicant's career goals. Additionally, one consultant will offer help in applicant's training and guidance. Min Zhuo, Ph.D., a neuroscientist with expertise in cellular electrophysiology, will provide training in spinal cord slice preparation. The applicant's goal is to acquire expertise to launch an independent career

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in pain research in the future. The applicant's research proposal addresses the role of multiple Ca2+ channels in sensory and nociceptive pathways in DRG and spinal cord. Even though voltage gated Ca2+ channels have long been recognized as targets for analgesic, anesthetic and anticonvulsant agents, progress in understanding the action of these channels on specific targets within sensory pathways has been impeded by the lack of selective tools to study their pharmacology. In the past two years, working on acutely dissociated rat DRG cells, the applicant has identified a novel selective antagonist for T-type Ca2+ channels, a neurosteroid (+)-ECN, which has minimal effects on other voltage- and receptor-gated channels. Another neurosteroid, (+)-ACN, shows remarkable selectivity for Q-, and R-subtypes of HVA Ca2+ channels and is a promising new tool to study HVA channels. Additionally, one of the most effective agents for treatment of neuropathic pain, the anticonvulsant phenytoin, blocks T-type current in DRG neurons in clinically relevant concentrations. The applicant proposes to follow up these findings with additional studies aimed at further clarifying the mechanisms and targets for these agents in acutely dissociated labeled spinothalamic dorsal horn neurons, isolated dendrites of dissociated dorsal horn neurons and their effects on synaptic transmission in DRG-dorsal horn co-cultures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL CORRELATES OF EMOTION Principal Investigator & Institution: Keele, Norman B.; Psychology and Neuroscience; Baylor University Waco, Tx 76798 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The long-term goal of this project is to develop and use a clinically relevant animal model of aggressive behavior. We hypothesize that low serotonin-induced aggression is associated with (1) changes in other emotional behavior and (2) increased membrane excitability in amygdala neurons. Impulsive-aggressive humans reportedly have low anxiety and are less sensitive to fear-conditioning. Similar to humans, it is proposed that anxious behaviors and fear-learning are correlated with aggression and low serotonin levels. In addition, aggression has been suggested to result from epilepsy-like processes in limbic areas. One limbic structure, the amygdala, has well-defined roles in both epilepsy and emotion, and seizure activity that involves the amygdala may be associated with aggression in humans. Thus, cellular mechanisms of neuronal excitability in the amygdala may have a functional role in aggressive behavior. Supporting this idea are clinical studies showing anti-aggressive effects of anticonvulsants in prison inmates and psychiatric patients. In this project rats are chronically treated with PCPA, a competitive inhibitor of serotonin synthesis, to significantly inhibit serotonin synthesis. Low serotonin is widely-implicated in aggression in many species. Aggressive behavior is quantified using a simple test of rodent aggression characterized by easily recognized, stereotypical behaviors. Preliminary data have shown that aggressive behavior in this model is inhibited by the anticonvulsant phenytoin, as others have shown with human aggression. The specific aims of this project are to (1) define the salient independent variables required to model impulsive aggression, and to examine the relationship between aggression, low brain serotonin, and changes in amygdala-dependent emotional behaviors such as anxiety and fear-learning; and (2) compare amygdala neuron membrane properties and neurotransmission in control and aggressive animals using whole cell voltage-clamp.An animal model is developed that shares behavioral, neurochemical, and pharmacological similarities with impulsive-aggression in humans. Also, the neural correlates of aggression are investigated using cellular physiological methods never before used to

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study aggressive behavior. This innovative proposal examines basic biological mechanisms of aberrant emotional behavior that are relevant to human psychopathology. By developing this animal model, future research efforts can yield important insight into the cellular neurobiology of complex emotional behaviors such as aggression, and may have important clinical implications for the treatment of psychiatric disorders involving inappropriate aggression such as bipolar disorder, borderline personality disorder or antisocial personality disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURODEVELOPMENT EFFECTS OF ANTIEPILEPTIC DRUGS Principal Investigator & Institution: Meador, Kimford J.; Professor; Neurology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract): The proposed investigation addresses an important health care issue for women and their children. The use of antiepileptic drugs (AEDs) in women of childbearing age for epilepsy and for other indications (e.g., pain and psychiatric disorders) is common, but physicians need additional data, which are critical to adequately advise and direct treatment in these women. Animal studies have clearly demonstrated that commonly employed AEDs impair behavioral neurodevelopment. The potential consequences of such cognitive and behavioral deficits in humans are severe in terms of both personal and societal costs. However, controversy exists on the following issue to be addressed by this proposal. Do the most commonly used AEDs have differential effects on neurobehavioral outcomes in children exposed in utero? The primary objective of this study is to differentiate the relative risks/benefits of three major AEDs in the treatment of women with epilepsy in terms of their children's neurobehavioral development after in utero exposure. The study objectives will be addressed by a prospective, parallel-group, cohort design, multi-center investigation enrolling three groups of pregnant women on AED monotherapy (carbamazepine, phenobarbital, and phenytoin). The primary outcome variables are IQ scores of the children and other measures of neurobehavioral development. The results of the study will impact the clinical management of women receiving these medications, and improve the health of their children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OUTCOMES ASSOCIATED WITH ANTIEPILEPTIC DRUGS IN ELDERLY Principal Investigator & Institution: Garrard, Judith M.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: Elderly people (age 65 years and older) are the most rapidly growing segment of the US population and the incidence of epilepsy is greatest in this age group. Little information is available about the use or outcomes associated with antiepileptic drugs (AEDs) by these vulnerable persons. We will examine pattems of AED use and associated outcomes among nursing home (NH) and community based elderly. For the proposed research, we have available two large electronic data sets: (1) the Beverly Enterprises Inc. centralized records (the Minimum Data Set and physicians' orders) for two calendar years (1999, 2000) for all residents (N~140,000 for two years) living in 501 NHs in 31 states, and (2) the Health Care Financing Administration's (HCFA) integration of the Medicare Current Beneficiaries Survey with Medicare claims files

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(N~12,000 elderly per year) for 7 calendar years. Both of these data sets have been used in part during the current project (1997-2002) by the same multidisciplinary team that will be working in the proposed project. We have a thorough working knowledge of the complexities of these data sets and the richness of information they contain. In our current research, we found a prevalence of 7.7% for AED use by NH admissions. Significant covadates with AED use at admission were epilepsy/seizure, bipolar depression, age group, and cognitive performance. During the first 3 months following admission, an additional 2.7% people were initiated on AEDs. Epilepsy/seizure indication was present in 5.8% of all admissions and an additional 1.47% of the followup cohort during the first 3 months. Specific aims of the proposed project are: (1) outcomes associated with any AED use by eldedy, (2) pharmacoepidemiology, characteristics, and outcomes associated with CBZ, PHT and VPA, and (3) the pharmacoepidemiology of other specific AEDs. Patient outcomes will be captured through incidence events, while AED use can be tracked continuously over time. Multivariate-modeling techniques will be used, controlling for demographics, comorbidities, and regional effects. Other P50 teams are studying the elimination kinetics of AEDs, and we will use this knowledge to develop age, gender and co-medication specific estimated total and unbound concentrations for NH residents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC PHARMACOLOGY RESEARCH UNIT Principal Investigator & Institution: Blumer, Jeffrey L.; Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2004; Project Start 29-SEP-1994; Project End 31-DEC-2008 Summary: (provided by applicant): This is an application for continuation of funding for the Cleveland Pediatric Pharmacology Research Unit (PPRU). Our unit was first funded in 1994, one year after the establishment of the PPRU and has been funded since then at a level one-half to two thirds that of the other units in the network. Despite this funding bias, Cleveland has been an active member of the Network. During the first four years we participated in 13 network protocols contributing 298 patients. The last five years have seen this trajectory in activity maintained. We have been the lead site on 28 protocols and participated overall in 69 network studies enrolling more than 657 children. We have also completed two major multisite studies designed and coordinated by the Cleveland PPRU that have subsequently been adopted by the drugs' innovators to support SNDA filings. In support of ongoing PPRU activities we have developed two print symposia, one dealing with the evaluation of antihypertensive agents in children and the other dealing with the treatment of sleep disorders in children, designed to set the stage for further clinical trials. Finally we are the lead site on the first PPRUexclusive multisite R01 application submitted to NIH. Our renewal application both details our accomplishments as a member of the PPRU Network and outlines our plans to expand our research base into several new therapeutic areas. To compliment our demonstrated expertise in pharmacokinetic/ pharmacodynamic modeling we propose a study to evaluate new approaches to study design that should add parsimony to our efforts at pediatric drug development. These approaches will be essential in support of the upcoming PPRU initiatives in response to the Best Pharmaceuticals for Children Act. We will also bring to the network a series of trials in the area of pediatric sleep disorders. We will also present approaches to the integration of pharmacogenetic approaches into the elucidation of novel mechanisms of adverse drug reactions in children. Finally, we will discuss our expanded training program in pediatric pharmacology research.

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

Project Title: PHARMACOEPIDEMIOLOGY OF THE ANTIEPILEPTIC DRUGS Principal Investigator & Institution: Birnbaum, Angela K.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: The incidence of epilepsy rises rapidly after age 60, and many elderly are being treated with phenytoin (PHT), carbamazepine (CBZ) and valproic acid (VPA). These older antiepileptic drugs (AEDs) have many shortcomings including complex metabolism by the cytochrome P450 and glucuronidation enzyme systems and have been shown to be inducers and inhibitors in these systems. This makes them prone to many drug interactions involving both clearance and protein binding. This is a multifaceted issue; AED efficacy and toxicity may be altered by co-medications, and AEDs can affect the efficacy and toxicity of co-medications. Because an elderly patient uses an average of 6 medications, the risk of medication interactions in this age group with these older AEDs is very high. Three newer AEDs, lamotrigine (LTG), topiramate (TPM) and levetiracetam (LEV) appear to have more favorable drug-drug interaction profiles; all have low protein binding and fewer or no metabolic interactions. However, these newer drugs have not been studied sufficiently in the eldedy and more detailed information regarding the pharmacokinetio and pharmacodynamic properties of these is needed. The difficulty in obtaining blood samples from this population makes inclusion in standard pharrnacokinetic studies difficult. This project will use nonlinear mixed effects model (NONMEM) that employs both pharmacokinetics and statistics will be used to determine pharrnacokinetic parameters of these three new drugs. This powerful method allows the use of routinely collected data to be used and avoids the risks and expense encountered in intensive pharmacokinetic studies. With this method, not only can the drug clearance be determined for a population, but it can also be determined for an individual. Factors (age, race, gender, smoking, etc.) that affect drug clearance can also be determined. In addition, the relationship between serum drug concentration and seizure type will be determined for LTG, TPM, and LEV. We will have access to approximately 450 persons >65 years of age receiving LTG, 420 receiving TPM and 337 receiving LEV from several active epilepsy practices in 3 cities (Minneapolis, Miami, Atlanta) and data from more than 1500 younger adults on each of these AEDs. In addition we will use our tools to analyze data from the ongoing perspective VA cooperative study of LTG projected to enroll 240 subjects receiving LTG as initial treatment. The VA data will determine the relationship between drug concentrations and adverse events and seizure frequency for LTG providing both pharmacokinetic and pharmacodynamic information in the elderly. This project along with Projects 1 and 2 will provide pharmacokinetic data and identify and quantitate the factors that influence the pharmacokinetics of LTG, LEV, and TPM. This information can be used to guide dosing requirements needed to obtain target serum concentrations in the elderly to achieve seizure control and avoid drug toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOGENOMIC STUDY OF ANTICONVULSANT THERAPY Principal Investigator & Institution: Ferraro, Thomas N.; Associate Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 29-JAN-2001; Project End 31-DEC-2003

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Summary: (adapted from applicant's abstract): Many patients with epilepsy are resistant to standard anticonvulsant drug (ACD) treatments. This proposal seeks to elucidate the origin of the genetic factors that affect individual response to ACDs by mapping the location of genes that influence these responses in mice. There are 2 phases to this proposal. Phase 1 involves identifying mouse strains best suited for dissecting the genetic influences which control response to specific ACDs. Phase 2 involves mapping these genetic influences to defined regions of the genome. In phase 1, strain-specific maximal electroshock seizure threshold (MEST) will be characterized. Strains with similar mean MESTs will be considered equivalently seizure-sensitive and such pairs of strains will be used for subesequent anticonvulsant drug (ACD) testing. ACD testing will involve dose-reponse studies with a panel of clinically relevant ACDs: phenytoin, carbamazepine, vaiproic acid and gamma-vinyl GABA. The quantitatve endpoint will be the absolute MEST determined in the presence of drug. Strains will be selected for quantitative trait loci (QTL) analyses based on their strain-specific response such that pairs of strains exhibiting the largest differential effects on MEST for a given drug (the strains showing the largest and smallest anticonvulsant effects) will be used for QTL studies. Brain levels of ACDs will be determined in parental strains in order to address one possible major co-phenotype in correlation with the anticonvulsant MEST response. In phase 2, QTL mapping studies will be conducted using mouse strains suggested by phase 1 phenotype studies. Mapping will utilize segregating F2 (intercross) populations for each strain pair. Quantitative phenotype for mapping will be MEST in individual F2 mice pretreated with a specific ACD. Brain ACD levels will be determined in F2 animals and used as a second quantitative phenotype for mapping. In order to distinguish ACD response QTLs from seizure sensitivity QTLs which may segregate in the cross, a parallel QTL study will be conducted for each ACD using an independent F2 population tested for MEST following saline rather than ACD pretreatement. QTL genotype and mapping experiments will combine a 15-20 cM genome scan with comprehensive statistical analyses including both parametric and non-parametric single and multilocus models. Results will lead to the direct localization of genes that influence anticonvulsant responses in mice with future directions involving the identification of these genes. The described studies build directly from the foundation of work in the investigator's lab on mapping mouse loci involved in differential sensitivity to chemically- and electricallyinduced seizures and ultimately will lead to a focused strategy for investigating genetic influences on response to anticonvulsant drugs in humans with epilepsy. The association of human anticonvulsant response with specific genomic variants will lead to more rational decisions regarding the choice of drug for individual patients and will lead to greater success in treating seizures disorders in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOKINETICS AND METABOLISM OF ANTIEPILEPTICS IN ELDERLY PATIENTS Principal Investigator & Institution: Cloyd, James C.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: Our goal is to investigate the effect of advanced age on antiepileptic drug pharmacokinetics and metabolism. Selected elderly and adult male and female ambulant patients taking phenytoin (PHT or CBZ) as monotherapy for epilepsy will be evaluated. The patients will receive a portion of their oral dose of PHT as stable-labeled PHT given intravenously as 100 mg over 5 minutes (one time only). Stable-labeled PHT

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is NOT radioactive and exhibits the same kinetics and metabolism as unlabeled PHT. Blood samples and urine collections will be analyzed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL LOSARTAN PHENYTOIN DRUG INTERACTIONS IN VOLUNTEERS Principal Investigator & Institution: Allen, Tracy J.; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGRESSION OF TEMPORAL LOBE EPILEPSY Principal Investigator & Institution: Dudek, Francis Edward.; Professor; Anatomy and Neurobiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Although epidemiological studies have provided valuable perspectives on temporal lobe epilepsy, the ethical limitations of human research prevent a definitive answer to the important question: is antiepileptic drug (AED) therapy purely symptomatic, or does it affect the natural history of the epilepsy? The proposed experiments use an animal model of temporal lobe epilepsy to determine whether spontaneous epileptic seizures damage the brain and increase the likelihood of more seizures (i.e., promote epileptogenesis), and conversely, whether decreasing the number of seizures with AEDs significantly reduces brain damage and epileptogenesis. The central hypothesis is that prolonged treatment with an AED, which significantly reduces spontaneous epileptic seizures, causes long-term reductions in the frequency and severity of subsequent epileptic seizures after AED withdrawal. The kainate-treated rat, a well-characterized animal model of temporal lobe epilepsy, will be used to determine whether the progressive increase in the frequency ofspontaneous seizures during the months after status epilepticus continues to damage the hippocampus and contributes to epileptogenesis. AEDs (i.e., phenytoin, phenobarbital, and valproate) will be used to block spontaneous epileptic seizures for prolonged periods to determine whether AED therapy reduces epileptogenesis and results in a long-term decrease in spontaneous seizure frequency (i.e., a decrease in frequency that persists after the AED therapy has been withdrawn). A related hypothesis is that prolonged AED treatment reduces neuronal death and other potential markers of hippocampal epileptogenesis. Chronic recording of electrographic seizures, quantitative histopathological studies, and in vitro electrophysiological recording of synaptic and epileptiform events in hippocampal slices will be used to determine if prolonged AED treatment decreases neuronal damage, reorganization of neural circuits, and epileptogenesis. These experiments will provide precise and valuable information regarding the influence of seizure frequency on brain damage and on the propensity for future seizures, which will be important for understanding the mechanisms of epileptogenesis and for making clinical decisions regarding AED therapy and epilepsy surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF CYP2B6 IN HUMAN LIVER Principal Investigator & Institution: Lecluyse, Edward L.; Drug Delivery & Disposition; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 13-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): The long-term goals of this project are to determine the molecular factors that govern the drug-induced regulation of cytochrome P450 2B6 (CYP2B6) in human liver. Historically overlooked as an enzyme of consequence, recent evidence suggests that CYP2B6 plays a larger role in the elimination of drugs than previously believed and its specific content within the livers of some individuals can rival that of CYP3A4 when induced by potent agents, such as rifampicin or phenytoin. In the past several years, the nuclear receptor CAR (constitutive androstane receptor) has been implicated as a key mediator of xenobiotic regulation of CYP2B genes in many species. More recently, cross-talk between PXR and CAR for binding promoter sequences of both CYP3A and CYP2B genes suggests that both receptors can play a role in the regulation of either P450 gene. Notably, we have observed a very high correlation between the drug-induced expression of CYP2B6 in human hepatocytes and the activation of hPXR. By contrast, none of the potent inducers of CYP2B6 that we have identified to date show significant activation of hCAR. These results strongly suggest that there are significant and important species-specific differences in nuclear receptor regulation of CYP2B genes. The exact nature and dynamics of the relationship between these nuclear receptors in the regulation of CYP2B6 remains unclear, but we hypothesize that it is predominantly determined by hPXR activation, not hCAR. Accordingly, the SPECIFIC AIMS of this proposal are to test the following hypotheses: 1) induction of CYP2B6 in primary cultures of human hepatocytes correlates with activation of hPXR, and not hCAR, 2) hPXR transactivates CYP2B6 gene expression through the PBREM response element, 3) a distal XREM-Iike enhancer module is involved in the transactivation of CYP2B6 expression by hPXR, and 4) there are fundamental differences in the cellular disposition and biochemical activation steps of hCAR and mCAR. The data derived from the proposed studies should provide substantial insight into the molecular mechanisms of CYP2B6 expression in humans, and thus allow for better predictions of drug-drug interactions with CYP2B6 substrates and inducers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK FACTORS FOR PHENYTOIN TOXICITY Principal Investigator & Institution: Hennessy, Sean P.; Assistant Professor; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 30-JUN-2006 Summary: This career development award is being sought by a doctoral-level clinical pharmacist nearing the completion of his PhD in Epidemiology who is fully committed to a career as an independent, federally-funded academic investigator in the pharmacoepidemiology of aging. The Candidate will use the proven "80% research / 20% clinical" career model, which will provide a source of clinical research questions as well as the infrastructure to conduct patient-oriented research. A three-phase career development plan has been formulated specifically to address gaps in the Candidate's background. In addition to the research project that will serve as the "core curriculum," the career development plan will further develop his focus on aging, and provide

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classroom and laboratory training in molecular and genetic epidemiology with the objective of enabling him to collaborative knowledgeably and effectively with laboratory scientists. In the latter phase of the award, the Candidate will develop additional research ideas, perform pilot studies, and apply for federal research (e.g., R01) funding. A formal career advisory process is an integral component of the career development plan. The research component of this proposal is a study of risk factors for severe neurologic phenytoin toxicity, which has been shown in multiple data sources to be one of the leading causes of serious adverse drug reactions, particularly in the elderly. The study will examine therapy- and patient-specific factors, including age and polymorphisms in the genes that express cytochrome P450 enzyme isoforms CYP2C19 and CYP2C9, which are responsible for phenytoin metabolism. The study design is a case-control study that is nested within the population of patients seen for seizure disorders within our health system. Concurrent surveillance in the three major hospitals in our health system will be used to identify potential cases, with controls being randomly selected from patients prescribed phenytoin for seizure disorders within our health system. This career development award will enable the Candidate to complete the development of the skills and experience that he will need to evolve into an independent academic investigator in the pharmacoepidemiology of aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAFETY AND EFFICACY OF TIAGABINE HCL AS ADJUNCTIVE TREATMENT Principal Investigator & Institution: Chang, Gregory Y.; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE BASED DRUG DESIGN Principal Investigator & Institution: Stroud, Robert M.; Professor; Biochemistry and Biophysics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 30-JUN-2005 Summary: The goal of this continuing application is to develop species selectivity in compounds that inhibit a single, essential function, so to develop a new paradigm that will leverage drug development across many species. The essential enzyme function is the well recognized anti-cancer target, human thymidylate synthase (TS), the ratelimiting enzyme that provides the sole de novo pathway for synthesis of the DNA-base dTMP from the RNA base dUMP. The structures of TSs from human and from four, often lethal human pathogenic organisms are being determined as the basis of antiproliferative drug development: these include Pneumocystis carinii, Cryptococcus neoformans, Cryptosporidoum parvum, and Toxoplasma gondii. These are each the source of major opportunistic infections that cause early death, especially in patients with AIDS. Five additional species may be included in assays for selectivity of inhibition, as the program progresses. These include TS's from protozoa that are responsible for major worldwide diseases: Plasmodium falciparum, malaria; Trypanosoma cruz,i Trypanosoma burcei (Chagas' disease); Mycobacterisum tuberculosis (Tuberculosis) and Leishmania major. Inhibitors of TS are to be developed based on 1. Derivatives of leads based on phenolpthalein, originally discovered at UCSF;

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so far these have lead to 100 fold specificity for Cryptococus versus human TS, and 1000 fold inhibition of bacterial versus human TS. 2. Structures of known anti-cancer lead compounds bound to TS. New leads indicate new chemical entities that can encode high selectivity. 3. Fragment assembly, in which small molecules that have inhibitory activity are linked together, thus enhancing the potency. Here Dr. Stroud seeks to develop a new paradigm in drug development that relies on screening for (weak) inhibitors first, followed by combination, versus and normal reverse of synthesis followed by screening. 4. De novo drug discovery deriving from phage-discovered peptidic lead inhibitors of TS. Crystal structures of compounds bound to TS will direct how well they can be conjugated to enhance potency for human TS, or for pathogen versus human TS. New drug leads are to be developed using iterative cycles of structure-based development, followed by assays for affinity and selectivity. Public domain access to the structures of therapeutic targets and technology will encourage their use by major pharmaceutical companies for the better design of therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRAUMATIC BRAIN INJURY CLINICAL TRIALS NETWORK Principal Investigator & Institution: Diaz-Arrastia, Ramon R.; Associate Professor; Neurological Surgery; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This is a revised proposal for a Clinical Site in the "Cooperative multicenter traumatic brain injury clinical trials network." The proposal aims to establish a Traumatic Brain Injury (TBI) Research Center in Dallas, Texas, to be based at Parkland Memorial Hospital (PMH), with the collaboration of the Baylor Institute for Rehabilitation (BIR). Both institutions are nationally recognized for neurosurgical, neurological, and rehabilitation care. Parkland is the major Level I Trauma Center in the North Texas area, serving a population of approximately 5 million. PMH averages approximately 350 admissions for TBI each year, and 140 of these are for moderately severe to severe brain injury. All TBI patients are evaluated by the Physical Medicine and Rehabilitation service, and appropriate rehabilitation followup is obtained. The great majority of patients are referred to one of two rehabilitation units, the rehabilitation unit at PMH and BIR. Both the Parkland rehabilitation unit and the TBI unit at BIR are collaborators on this project. The PI, Dr. Eugene George, is Chief of the Neurosurgical Service at PMH. He has experience in multicenter collaborative trials in TBI, subarachnoid hemorrhage, and spinal cord injury. The other collaborators in the project all have an academic and clinical commitment to the care of patients with TBI. Dr. Lisa-Ann Wuermser is director of the Physical Medicine and Rehabilitation service at PMH, and an active investigator on trials on SCI and TBI. Dr. Mary Carlile is director of the TBI Program at BIR, and is widely recognized for excellence in management of these patients. Dr. Ramon Diaz-Arrastia is a neurologist and clinical neurophysiologist who is interested in the mechanisms of brain injury. Dr. Munro Cullum is Director of Neuropsychology at UT Southwestern, and has an extensive record of successful collaborative research in TBI and other neurodegenerative diseases. The concept proposal incorporated into this submission aims to determine the efficacy and value of continuous video-EEG (CVEEG) monitoring in patients with moderatelysevere to severe TBI. Recent technical advances have made this possible, and small uncontrolled studies indicate that a significant fraction of patients with TBI have subtle nonconvulsive seizures (NCS), that would not be recognized unless CVEEG is performed. The concept proposal aims to determine whether aggressive treatment of NCS results in improved functional outcome.

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Phenytoin

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

Project Title: TREATMENT OF STATUS EPILEPTICUS Principal Investigator & Institution: Kapur, Jaideep; Associate Professor; Neurology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2003 Summary: (Verbatim from the Applicant's Abstract) Convulsive status epilepticus is a prolonged self sustaining seizure which results in high morbidity and mortality. Current treatment of status epilepticus rests primarily on drugs that activate GABM receptors. GABAergic drugs are only effective in initiation phase of status epilepticus and lose effectiveness in sustained status epilepticus. When these drugs and phenytoin fail status epilepticus is treated with prolonged general anesthesia which is associated with high morbidity and mortality. A new class of drugs is necessary for the treatment of sustained status epilepticus. Preliminary studies find that NMDA receptor antagonists are effective in terminating sustained status epilepticus. Further, there is a potential mechanism of NMDA receptor activation during status epilepticus. NMDA receptors are only partially activated during normal low frequency excitatory synaptic activity in the hippocampus due to magnesium block of the receptor. This block can however be relieved by membrane depolarization. Compared to CA1 pyramidal neurons acutely isolated from control animals, the CA1 pyramidal neurons from animals in sustained status epilepticus have a markedly depolarized membrane potential. This depolarization is likely to remove Mg2+ block of NMDA receptors allow their activation. The proposal seeks to extend studies on NMDA receptor mechanisms in sustaining status epilepticus by testing two hypotheses. First, NMDA receptor antagonists are superior to conventional GABAergi c agents in terminating sustained (>60 minutes) status epilepticus and second there is increased activation of NMDA receptors on CA1 pyramidal neurons during sustained status epilepticus. The overall design of experiments seeks to combine insights from NMDA receptor antagonist treatment of experimental status epilepticus with patch clamp analysis of NMDA receptor currents in hippocampal CA1 pyramidal neurons acutely isolated from rats undergoing status epilepticus. This proposal tests hypotheses by fulfilling specific aims: 1) Comparing the efficacy of four classes of NMDA receptor antagonists with two GABAergic agents in controlling sustained status epilepticus and 2) Characterizing the resting membrane potential, NMDA and sensitivity, pH and redox sensitivity of NMDA receptors on CA1 neurons acutely isolated from hippocampi of rats undergoing sustained status epilepticus. These studies will provide animal data to design and execute human clinical trails for treatment of refractory status epilepticus with NMDA receptor antagonists. These studies will provide insights into mechanisms of NMDA receptor activation on vulnerable neurons during status epilepticus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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 3

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

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

A case of hypersensitivity syndrome due to phenytoin. Author(s): Nagai Y, Hattori T, Ishikawa O. Source: The Journal of Dermatology. 2002 October; 29(10): 670-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433002

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A case of phenytoin hypersensitivity syndrome. Author(s): Monks G, Crowson AN, Cornelison R, Naylor M. Source: J Drugs Dermatol. 2002 September; 1(2): 199-201. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847747

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A comparison of topical honey and phenytoin in the treatment of chronic leg ulcers. Author(s): Oluwatosin OM, Olabanji JK, Oluwatosin OA, Tijani LA, Onyechi HU. Source: Afr J Med Med Sci. 2000 March; 29(1): 31-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11379464

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A comparison of topical Phenytoin with Silverex in the treatment of superficial dermal burn wounds. Author(s): Carneiro PM, Rwanyuma LR, Mkony CA. Source: Cent Afr J Med. 2002 September-October; 48(9-10): 105-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562531

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A continuous quality improvement program for phenytoin i.v. Author(s): Matanin D, Cutrell D. Source: Hospital Formulary. 1994 March; 29(3): 212-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10132694

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A double-blind placebo-controlled crossover study of phenytoin in individuals with impulsive aggression. Author(s): Stanford MS, Houston RJ, Mathias CW, Greve KW, Villemarette-Pittman NR, Adams D. Source: Psychiatry Research. 2001 September 20; 103(2-3): 193-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549407

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 generalized seizure following initiation of nelfinavir in a patient with human immunodeficiency virus type 1 infection, suspected due to interaction between nelfinavir and phenytoin. Author(s): Honda M, Yasuoka A, Aoki M, Oka S. Source: Intern Med. 1999 March; 38(3): 302-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10337948

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A randomized, crossover, assessor-blind study of the bioequivalence of a single oral dose of 200 mg of four formulations of phenytoin sodium in healthy, normal Indian volunteers. Author(s): Gogtay NJ, Dalvi SS, Mhatre RB, Kirodian BG, Gupta AH, Jadhav SP, Kshirsagar NA. Source: Therapeutic Drug Monitoring. 2003 April; 25(2): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657917

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A study of the pharmacokinetics of phenytoin (diphenylhydantoin) in epileptic patients, and the development of a nomogram for making dose increments. Author(s): Richens A. Source: Epilepsia. 1975 November; 16(4): 627-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890790

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A very early onset of respiratory failure due to phenytoin-associated hypersensitivity syndrome and concomitant glucocorticoid administration. Author(s): Troger U, Brandt W, Rose W. Source: Intensive Care Medicine. 2000 February; 26(2): 258. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10784327

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Absence of an inhibitory effect of omeprazole and nizatidine on phenytoin disposition, a marker of CYP2C activity. Author(s): Bachmann KA, Sullivan TJ, Jauregui L, Reese JH, Miller K, Levine L. Source: British Journal of Clinical Pharmacology. 1993 October; 36(4): 380-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959321

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Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined by new technique. Author(s): Browne TR, Szabo GK, Leppik IE, Josephs E, Paz J, Baltes E, Jensen CM. Source: Journal of Clinical Pharmacology. 2000 June; 40(6): 590-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10868309

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Absorption of phenytoin from rectal suppositories formulated with a polyethylene glycol base. Author(s): Burstein AH, Fisher KM, McPherson ML, Roby CA. Source: Pharmacotherapy. 2000 May; 20(5): 562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10809343

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Absorption of rectally administered phenytoin: a pilot study. Author(s): Chang SW, da Silva JH, Kuhl DR. Source: The Annals of Pharmacotherapy. 1999 July-August; 33(7-8): 781-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466903

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Acute fulminant hepatic failure in a woman treated with phenytoin and trimethoprim-sulfamethoxazole. Author(s): Ilario MJ, Ruiz JE, Axiotis CA. Source: Archives of Pathology & Laboratory Medicine. 2000 December; 124(12): 1800-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11100060

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Acute psychosis due to treatment with phenytoin in a nonepileptic patient. Author(s): Gatzonis SD, Angelopoulos E, Sarigiannis P, Mantouvalos V, Ploumbidis D, Siafakas A. Source: Epilepsy & Behavior : E&B. 2003 December; 4(6): 771-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698717

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Acute tacrolimus overdose and treatment with phenytoin in liver transplant recipients. Author(s): Karasu Z, Gurakar A, Carlson J, Pennington S, Kerwin B, Wright H, Nour B, Sebastian A. Source: J Okla State Med Assoc. 2001 April; 94(4): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11392178

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Adaptation of total phenytoin reagent pack for measuring free phenytoin levels with the Abbott AxSYM immunoassay analyzer. Author(s): Jarzabek JI, Kampa IS. Source: Therapeutic Drug Monitoring. 1999 February; 21(1): 134-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051067

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Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study. Author(s): De Santis A, Villani R, Sinisi M, Stocchetti N, Perucca E. Source: Epilepsia. 2002 February; 43(2): 175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903465

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Administration of phenytoin and cytomegalovirus infection in the terminal ileum. Author(s): Yukawa M, Iizuka M, Sasaki K, Horie Y, Shirasaka T, Kon-no S, Watanabe S. Source: Journal of Gastroenterology and Hepatology. 2002 November; 17(11): 1240-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453289

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Adverse effects of phenytoin given for late-onset seizures in adults with Down syndrome. Author(s): Tsiouris JA, Patti PJ, Tipu O, Raguthu S. Source: Neurology. 2002 September 10; 59(5): 779-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221182

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Adverse events associated with intravenous phenytoin in children: a prospective study. Author(s): Appleton RE, Gill A. Source: Seizure : the Journal of the British Epilepsy Association. 2003 September; 12(6): 369-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915082

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Ageusia as an adverse effect of phenytoin treatment. Author(s): Zeller JA, Machetanz J, Kessler C. Source: Lancet. 1998 April 11; 351(9109): 1101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9660584

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Altered irinotecan metabolism in a patient receiving phenytoin. Author(s): Mathijssen RH, Sparreboom A, Dumez H, van Oosterom AT, de Bruijn EA. Source: Anti-Cancer Drugs. 2002 February; 13(2): 139-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11901305

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Altered phenytoin pharmacokinetics in children with severe, acute traumatic brain injury. Author(s): Stowe CD, Lee KR, Storgion SA, Phelps SJ. Source: Journal of Clinical Pharmacology. 2000 December; 40(12 Pt 2): 1452-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185666

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An algorithm for monitoring phenytoin therapy. Author(s): Crowder KM. Source: Journal of the American Academy of Nurse Practitioners. 2000 August; 12(8): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11930452

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Aplastic anemia induced by phenytoin: a geriatric case with severe folic acid deficiency. Author(s): Blain H, Hamdan KA, Blain A, Jeandel C. Source: Journal of the American Geriatrics Society. 2002 February; 50(2): 396-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028229

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Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders. Author(s): Dessens AB, Cohen-Kettenis PT, Mellenbergh GJ, Koppe JG, Poll NE, Boer K. Source: Teratology. 2001 October; 64(4): 181-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11598924

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Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems. Author(s): Dessens AB, Cohen-Kettenis PT, Mellenbergh GJ, Koppe JG, van De Poll NE, Boer K. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 May; 89(5): 533-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10852187

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Augmentation of the rocuronium-induced neuromuscular block by the acutely administered phenytoin. Author(s): Spacek A, Nickl S, Neiger FX, Nigrovic V, Ullrich OW, Weindmayr-Goettel M, Schwall B, Taeger K, Kress HG. Source: Anesthesiology. 1999 June; 90(6): 1551-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10360851

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Basis of the antiseizure action of phenytoin. Author(s): Tunnicliff G. Source: General Pharmacology. 1996 October; 27(7): 1091-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8981053

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Benefits of a clinical pharmacokinetic service in optimising phenytoin use in the western Cape. Author(s): Valodia P, Seymour MA, Kies BM, Folb PI. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1998 July; 88(7): 873-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9698715

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Bioactivation of phenytoin by human cytochrome P450: characterization of the mechanism and targets of covalent adduct formation. Author(s): Munns AJ, De Voss JJ, Hooper WD, Dickinson RG, Gillam EM. Source: Chemical Research in Toxicology. 1997 September; 10(9): 1049-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9305589

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Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings. Author(s): Doak KK, Haas CE, Dunnigan KJ, Reiss RA, Reiser JR, Huntress J, Altavela JL. Source: Pharmacotherapy. 1998 May-June; 18(3): 637-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9620116

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Bioavailability of phenytoin sodium capsules available in Thailand. Part II: In vivo study. Author(s): Suthisisang C, Payakachat N, Chulavatnatol S, Towanabut S. Source: J Med Assoc Thai. 1998 January; 81(1): 64-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9470324

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Bronchiolitis obliterans with organizing pneumonia and cold agglutinin disease associated with phenytoin hypersensitivity syndrome. Author(s): Angle P, Thomas P, Chiu B, Freedman J. Source: Chest. 1997 December; 112(6): 1697-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9404778

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Buffer capacity and precipitation control of pH solubilized phenytoin formulations. Author(s): Alvarez-Nunez FA, Yalkowsky SH. Source: International Journal of Pharmaceutics. 1999 August 5; 185(1): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425364

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Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. Author(s): Lakehal F, Wurden CJ, Kalhorn TF, Levy RH. Source: Epilepsy Research. 2002 December; 52(2): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458024

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Carbamazepine versus phenytoin monotherapy for epilepsy. Author(s): Tudur Smith C, Marson AG, Clough HE, Williamson PR. Source: Cochrane Database Syst Rev. 2002; (2): Cd001911. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076427

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Cardiac arrest after fast intravenous infusion of phenytoin mistaken for fosphenytoin. Author(s): DeToledo JC, Lowe MR, Rabinstein A, Villaviza N. Source: Epilepsia. 2001 February; 42(2): 288. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240605

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Cerebellar atrophy following acute phenytoin intoxication. Author(s): Alioglu Z, Sari A, Velioglu SK, Ouml;zmenoglu M. Source: Journal of Neuroradiology. Journal De Neuroradiologie. 2000 March; 27(1): 52-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10891781

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Cerebellar atrophy in an epileptic child: is it due to phenytoin? Author(s): Ahuja SR, Karande S, Kulkarni MV. Source: Journal of Postgraduate Medicine. 2000 October-December; 46(4): 278-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435657

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Cerebellar volume and long-term use of phenytoin. Author(s): De Marcos FA, Ghizoni E, Kobayashi E, Li LM, Cendes F. Source: Seizure : the Journal of the British Epilepsy Association. 2003 July; 12(5): 312-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810345

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Changes in phenytoin concentrations in blood and cerebrospinal fluid caused by direct hemoperfusion in a patient intoxicated with phenytoin. Author(s): Kanayama Y, Itakura Y, Iwasaki M, Hirahara Y, Takasino S, Kawase Y, Katoh H, Kinosita M, Matsumura O, Mitarai T, Isoda K. Source: Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis. 1998 February; 2(1): 74-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227793

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Charcoal hemoperfusion in the treatment of phenytoin overdose. Author(s): Kawasaki C, Nishi R, Uekihara S, Hayano S, Otagiri M. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 February; 35(2): 323-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10676735

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Chondrodysplasia punctata (CDP) with features of the tibia-metacarpal type and maternal phenytoin treatment during pregnancy. Author(s): Wester U, Brandberg G, Larsson M, Lonnerholm T, Anneren G. Source: Prenatal Diagnosis. 2002 August; 22(8): 663-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210573

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Class III antiarrhythmics and phenytoin: teratogenicity due to embryonic cardiac dysrhythmia and reoxygenation damage. Author(s): Danielsson BR, Skold AC, Azarbayjani F. Source: Current Pharmaceutical Design. 2001 June; 7(9): 787-802. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11375779

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Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy. Author(s): Knapp LE, Kugler AR. Source: Journal of Child Neurology. 1998 October; 13 Suppl 1: S15-8; Discussion S30-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9796747

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Clinical experience with fosphenytoin in children. Author(s): Morton LD. Source: Journal of Child Neurology. 1998 October; 13 Suppl 1: S19-22; Discussion S30-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9796748

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Coadministration of phenytoin and felbamate: evidence of additional phenytoin dose-reduction requirements based on pharmacokinetics and tolerability with increasing doses of felbamate. Author(s): Sachdeo R, Wagner ML, Sachdeo S, Shumaker RC, Lyness WH, Rosenberg A, Ward D, Perhach JL. Source: Epilepsia. 1999 August; 40(8): 1122-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448826

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Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Author(s): Purkins L, Wood N, Ghahramani P, Love ER, Eve MD, Fielding A. Source: British Journal of Clinical Pharmacology. 2003 December; 56 Suppl 1: 37-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616412

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Comment: phenytoin/isradipine interaction causing severe neurologic toxicity. Author(s): Hauben M. Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1974-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452767

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Comment: unexpectedly low phenytoin concentration in a patient receiving ciprofloxacin. Author(s): McLeod R, Trinkle R. Source: The Annals of Pharmacotherapy. 1998 October; 32(10): 1110-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9793610

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Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects. Author(s): Beenen LF, Lindeboom J, Kasteleijn-Nolst Trenite DG, Heimans JJ, Snoek FJ, Touw DJ, Ader HJ, van Alphen HA. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 October; 67(4): 47480. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10486394

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Comparing a mass-balance algorithm with a Bayesian regression analysis computer program for predicting serum phenytoin concentrations. Author(s): Choy M, Winter ME. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1998 November 15; 55(22): 2392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825035

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Comparison between premortem and postmortem serum concentrations of phenobarbital, phenytoin, carbamazepine and its 10,11-epoxide metabolite in institutionalized patients with epilepsy. Author(s): May T, Jurgens U, Rambeck B, Schnabel R. Source: Epilepsy Research. 1999 January; 33(1): 57-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10022366

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Comparison of phenytoin serum concentrations in premature neonates following intravenous and oral administration. Author(s): Frey OR, von Brenndorff AI, Probst W. Source: The Annals of Pharmacotherapy. 1998 March; 32(3): 300-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9533059

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Comparison of total and free phenytoin serum concentrations measured by highperformance liquid chromatography and standard TDx assay: implications for the prediction of free phenytoin serum concentrations. Author(s): May TW, Rambeck B, Jurges U, Blankenhorn V, Jurgens U. Source: Therapeutic Drug Monitoring. 1998 December; 20(6): 619-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853976

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Concomitant use of mirtazapine and phenytoin: a drug-drug interaction study in healthy male subjects. Author(s): Spaans E, van den Heuvel MW, Schnabel PG, Peeters PA, Chin-Kon-Sung UG, Colbers EP, Sitsen JM. Source: European Journal of Clinical Pharmacology. 2002 September; 58(6): 423-9. Epub 2002 August 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242602

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Construction and application of phenytoin anion-selective electrode based on bulk acoustic wave (BAW) sensing technique. Author(s): Long Y, Liu Y, Lei L, Nie L, Yao S. Source: The Analyst. 2001 July; 126(7): 1090-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11478641

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Controversy over administration of phenytoin. Author(s): Nielson K. Source: Critical Care Nurse. 2001 August; 21(4): 18, 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858683

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Correlation and prediction of phenytoin protein binding using standard laboratory parameters in patients after renal transplantation. Author(s): Monaghan MS, Marx MA, Olsen KM, Turner PD, Bergman KL. Source: Therapeutic Drug Monitoring. 2001 June; 23(3): 263-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11360036

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Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department. Author(s): Touchette DR, Rhoney DH. Source: Pharmacotherapy. 2000 August; 20(8): 908-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10939551

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Craniofacial skeletal deviations following in utero exposure to the anticonvulsant phenytoin: monotherapy and polytherapy. Author(s): Orup HI Jr, Holmes LB, Keith DA, Coull BA. Source: Orthodontics & Craniofacial Research. 2003 February; 6(1): 2-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627792

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Cross-reactivity of fosphenytoin in two human plasma phenytoin immunoassays. Author(s): Kugler AR, Annesley TM, Nordblom GD, Koup JR, Olson SC. Source: Clinical Chemistry. 1998 July; 44(7): 1474-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9665426

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Cutaneous reactions in patients with solitary cysticercus granuloma on phenytoin sodium. Author(s): Singh G, Kaushal S, Gupta M, Chander Chopra S. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 February; 75(2): 3313. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742623

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CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects. Author(s): Soga Y, Nishimura F, Ohtsuka Y, Araki H, Iwamoto Y, Naruishi H, Shiomi N, Kobayashi Y, Takashiba S, Shimizu K, Gomita Y, Oka E. Source: Life Sciences. 2004 January 2; 74(7): 827-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659971

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Data vs opinion, phenytoin vs fosphenytoin: the saga continues. Author(s): Labiner DM. Source: Archives of Internal Medicine. 1999 December 13-27; 159(22): 2631-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10597752

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Debate over use of phenytoin. Author(s): Bey P, Bey TA. Source: Critical Care Nurse. 2001 February; 21(1): 21-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858240

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Decreased total antioxidant capacity and elevated lipid hydroperoxide concentrations in sera of epileptic patients receiving phenytoin. Author(s): Mahle C, Dasgupta A. Source: Life Sciences. 1997; 61(4): 437-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9244370

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Determination of free levels of phenytoin in human plasma by liquid chromatography/tandem mass spectrometry. Author(s): Bardin S, Ottinger JC, Breau AP, O'Shea TJ. Source: Journal of Pharmaceutical and Biomedical Analysis. 2000 August 15; 23(2-3): 573-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933551

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Determination of lamotrigine simultaneously with carbamazepine, carbamazepine epoxide, phenytoin, phenobarbital, and primidone in human plasma by SPME-GCTSD. Author(s): Queiroz ME, Silva SM, Carvalho D, Lancas FM. Source: Journal of Chromatographic Science. 2002 April; 40(4): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004942

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Determination of phenytoin in human plasma by gas chromatography. Author(s): Zarghi A, Gholami K, Hessami M. Source: Boll Chim Farm. 1999 November; 138(10): 508-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765466

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Determination of phenytoin in plasma by molecularly imprinted solid-phase extraction. Author(s): Bereczki A, Tolokan A, Horvaia G, Horvath V, Lanza F, Hall AJ, Sellergren B. Source: J Chromatogr A. 2001 September 28; 930(1-2): 31-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11681577

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Determination of phenytoin in sections of head hair: a preliminary study to evaluate the history of drug use. Author(s): Tsatsakis AM, Psillakis T, Stefis A, Assithianakis P, Vlahonikolis IG, Michalodimitrakis MN, Helidonis E. Source: Boll Chim Farm. 1998 December; 137(11): 459-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10077879

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Development of a pulmonary phenytoin-associated hypersensitivity reaction despite concomitant dexamethasone and prednisolone administration. Author(s): Troger U, Brandt W, Rose W. Source: Int J Clin Pharmacol Ther. 2000 September; 38(9): 452-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020034

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Developmental changes in the liver weight- and body weight-normalized clearance of theophylline, phenytoin and cyclosporine in children. Author(s): Kanamori M, Takahashi H, Echizen H. Source: Int J Clin Pharmacol Ther. 2002 November; 40(11): 485-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698985

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Dexamethasone/phenytoin interactions: neurooncological concerns. Author(s): Ruegg S. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 July 27; 132(29-30): 425-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428189

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Differential kinetics of phenytoin in elderly patients. Author(s): Bachmann KA, Belloto RJ Jr. Source: Drugs & Aging. 1999 September; 15(3): 235-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10503815

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Diffusion tensor MRI and fiber tractography of cerebellar atrophy in phenytoin users. Author(s): Lee SK, Mori S, Kim DJ, Kim SY, Kim SY, Chu M, Heo K, Lee BI, Kim DI. Source: Epilepsia. 2003 December; 44(12): 1536-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636324

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Dilantin as anticonvulsant in eclampsia. Author(s): Bathla S, Suneja A, Guleria K, Agarwal N. Source: J Indian Med Assoc. 2002 September; 100(9): 561-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455387

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Dilantin jeopardy: avoiding the dangers of phenytoin. Author(s): Schlicher ML. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 1998 December; 7(6): 343-7, 356. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10036438

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Dissolving phenytoin precipitate in central venous access device. Author(s): Tse CS, Abdullah R. Source: Annals of Internal Medicine. 1998 June 15; 128(12 Pt 1): 1049. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625676

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Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy? Author(s): Genton P, Gelisse P, Thomas P, Dravet C. Source: Neurology. 2000 October 24; 55(8): 1106-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11071486

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Drug-drug interaction in reverse: possible loss of phenytoin efficacy as a result of fluoxetine discontinuation. Author(s): Shad MU, Preskorn SH. Source: Journal of Clinical Psychopharmacology. 1999 October; 19(5): 471-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10505590

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Drug-induced gingival overgrowth after phenytoin and nifedipine therapy. A case report. Author(s): Slezak R. Source: J West Soc Periodontol Periodontal Abstr. 1997; 45(4): 105-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9571890

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Dyskinesia induced by phenytoin. Author(s): Montenegro MA, Scotoni AE, Cendes F. Source: Arquivos De Neuro-Psiquiatria. 1999 June; 57(2B): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10450338

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Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact more than protein binding. Author(s): Tang C, Lin Y, Rodrigues AD, Lin JH. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 June; 30(6): 648-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019190

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Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Author(s): Davit BM, Singh GJ, Conner DP. Source: Neurology. 2002 February 26; 58(4): 666-7; Author Reply 666-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11865159

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Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Author(s): Wilder BJ, Leppik I, Hietpas TJ, Cloyd JC, Randinitis EJ, Cook J. Source: Neurology. 2001 August 28; 57(4): 582-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11524464

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Effect of heating human sera at a temperature necessary to deactivate human immunodeficiency virus on measurement of free phenytoin, free valproic acid, and free carbamazepine concentrations. Author(s): Dasgupta A, Wells A, Chow L. Source: Therapeutic Drug Monitoring. 1999 August; 21(4): 421-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442696

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Effect of mild therapeutic hypothermia on phenytoin pharmacokinetics. Author(s): Iida Y, Nishi S, Asada A. Source: Therapeutic Drug Monitoring. 2001 June; 23(3): 192-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11360024

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Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures. Author(s): Rafi JA, Frazier LM, Driscoll-Bannister SM, O'Hara KA, Garnett WR, Pugh CB. Source: The Annals of Pharmacotherapy. 1999 July-August; 33(7-8): 769-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466901

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Effect of phenytoin on the production of interleukin-6 and interleukin-8 in human gingival fibroblasts. Author(s): Modeer T, Domeij H, Anduren I, Mustafa M, Brunius G. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2000 November; 29(10): 491-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11048965

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Effect of sex on serum protein binding characteristics of phenytoin in pediatric patients with epilepsy. Author(s): Kodama H, Kodama Y, Itokazu N, Arimori K, Kanemaru R, Sugimoto T, Fujimura A. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 June 15; 57(12): 1144-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10911514

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Effect of temperature on binding characteristics of phenytoin to serum proteins in monotherapy adult patients with epilepsy. Author(s): Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y. Source: American Journal of Therapeutics. 2000 January; 7(1): 11-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11319568

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Effect of temperature on serum protein binding characteristics of phenytoin in monotherapy paediatric patients with epilepsy. Author(s): Kodama H, Kodama Y, Itokazu N, Shinozawa S, Kanemaru R, Sugimoto T. Source: Journal of Clinical Pharmacy and Therapeutics. 2001 June; 26(3): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422600

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Effects of phenytoin on cocaine self-administration in humans. Author(s): Sofuoglu M, Pentel PR, Bliss RL, Goldman AI, Hatsukami DK. Source: Drug and Alcohol Dependence. 1999 February 1; 53(3): 273-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10080053

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Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Author(s): Gallagher EP, Sheehy KM. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2001 January; 59(1): 118-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11134551

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Efficacy of magnesium sulphate and phenytoin in the management of eclampsia. Author(s): Sawhney H, Sawhney IM, Mandal R, Subramanyam, Vasishta K. Source: The Journal of Obstetrics and Gynaecology Research. 1999 October; 25(5): 333-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10533328

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Efficacy of phenytoin against hyponatremic seizures due to SIADH after administration of anticancer drugs in a neonate. Author(s): Okamoto M, Nako Y, Tachibana A, Fujiu T, Ohki Y, Tomomasa T, Morikawa A. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 April-May; 22(3): 247-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948390

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Efficacy of statin therapy: possible effect of phenytoin. Author(s): Murphy MJ, Dominiczak MH. Source: Postgraduate Medical Journal. 1999 June; 75(884): 359-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435174

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Elevated serum phenytoin concentrations associated with coadministration of sertraline. Author(s): Haselberger MB, Freedman LS, Tolbert S. Source: Journal of Clinical Psychopharmacology. 1997 April; 17(2): 107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950473

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Elimination of phenytoin in toxic overdose. Author(s): Chua HC, Venketasubramanian N, Tjia H, Chan SP. Source: Clinical Neurology and Neurosurgery. 2000 March; 102(1): 6-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10717394

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Enantioselective induction of cyclophosphamide metabolism by phenytoin. Author(s): Williams ML, Wainer IW, Embree L, Barnett M, Granvil CL, Ducharme MP. Source: Chirality. 1999; 11(7): 569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10423284

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Ephedrine-induced complete atrioventricular block with ventricular asystole during rapid concomitant phenytoin infusion: a case report. Author(s): Lin SY, Wu CT, Yeh CC, Liu ST, Ho ST, Wong CS. Source: Acta Anaesthesiol Sin. 1999 March; 37(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10407528

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Epilepsy and pregnancy: maternal and fetal effects of phenytoin. Author(s): Brewer JM, Waltman PA. Source: Critical Care Nurse. 2003 April; 23(2): 93-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725198

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Epilepsy control with phenobarbital or phenytoin in rural south India: the Yelandur study. Author(s): Mani KS, Rangan G, Srinivas HV, Srindharan VS, Subbakrishna DK. Source: Lancet. 2001 April 28; 357(9265): 1316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343735

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Erythema multiforme possibly due to phenytoin. Author(s): Marinella MA. Source: The Annals of Pharmacotherapy. 1999 June; 33(6): 748. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410191

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Evaluation of fluorescence polarization assays for measuring valproic acid, phenytoin, carbamazepine and phenobarbital in serum. Author(s): Steijns LS, Bouw J, van der Weide J. Source: Therapeutic Drug Monitoring. 2002 June; 24(3): 432-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021637

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Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers. Author(s): Fischer TL, Pieper JA, Graff DW, Rodgers JE, Fischer JD, Parnell KJ, Goldstein JA, Greenwood R, Patterson JH. Source: Clinical Pharmacology and Therapeutics. 2002 September; 72(3): 238-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235444

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Evidence for the involvement of bone morphogenetic protein-2 in phenytoinstimulated osteocalcin secretion in human bone cells. Author(s): Koyama H, Nakade O, Saitoh T, Takuma T, Kaku T. Source: Archives of Oral Biology. 2000 August; 45(8): 647-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10869476

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Evidence-based implementation of free phenytoin therapeutic drug monitoring. Author(s): Burt M, Anderson DC, Kloss J, Apple FS. Source: Clinical Chemistry. 2000 August; 46(8 Pt 1): 1132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10926893

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Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin. Author(s): Saito K, Mori S, Tanda N, Sakamoto S. Source: J Periodontol. 1999 June; 70(6): 581-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10397512

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Extravasation injury of the upper extremity by intravenous phenytoin. Author(s): Edwards JJ, Bosek V. Source: Anesthesia and Analgesia. 2002 March; 94(3): 672-3; Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11867395

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Extremely acute phenytoin-induced peripheral neuropathy. Author(s): Yoshikawa H, Abe T, Oda Y. Source: Epilepsia. 1999 April; 40(4): 528-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10219285

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Factors influencing phenytoin-induced gingival enlargement. Author(s): Majola MP, McFadyen ML, Connolly C, Nair YP, Govender M, Laher MH. Source: Journal of Clinical Periodontology. 2000 July; 27(7): 506-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914892

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Factors influencing the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa. Author(s): Valodia P, Seymour MA, Miller R, McFadyen ML, Folb PI. Source: Therapeutic Drug Monitoring. 1999 February; 21(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051055

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Falsely increased immunoassay measurements of total and unbound phenytoin in critically ill uremic patients receiving fosphenytoin. Author(s): Roberts WL, De BK, Coleman JP, Annesley TM. Source: Clinical Chemistry. 1999 June; 45(6 Pt 1): 829-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10351992

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Falsely positive dexamethasone suppression test in a patient treated with phenytoin to prevent seizures due to nocardia brain abscesses. Author(s): Debrunner J, Schmid C, Schneemann M. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 May 18; 132(19-20): 267. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12148082

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Fatal case of accidental intra-arterial phenytoin injection. Author(s): McLean CR, Cheng KS, Clifton MA. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2002 April; 23(4): 378-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11991707

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Fatal phenytoin hypersensitivity syndrome. Author(s): Mahadeva U, Al-Mrayat M, Steer K, Leen E. Source: Postgraduate Medical Journal. 1999 December; 75(890): 734-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10567602

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Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Author(s): Komatsu T, Yamazaki H, Asahi S, Gillam EM, Guengerich FP, Nakajima M, Yokoi T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 November; 28(11): 1361-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11038165

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Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Author(s): DeToledo JC, Ramsay RE. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2000 June; 22(6): 459-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10877039

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Fosphenytoin and status epilepticus. Author(s): Brown J. Source: Hosp Med. 1999 January; 60(1): 70-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197108

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Fosphenytoin facts. Author(s): Chioffi SM, Lassiter TF, Scates AC, McLendon BM. Source: The American Journal of Nursing. 1999 August; 99(8): 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10456012

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Fosphenytoin for seizure control. Author(s): Hutt N. Source: The American Journal of Nursing. 1999 March; 99(3): 52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10091570

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Fosphenytoin in infants of extremely low birth weight. Author(s): Kriel RL, Cifuentes RF. Source: Pediatric Neurology. 2001 March; 24(3): 219-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11301224

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Fosphenytoin in infants. Author(s): Takeoka M, Krishnamoorthy KS, Soman TB, Caviness VS Jr. Source: Journal of Child Neurology. 1998 November; 13(11): 537-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853645

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Fosphenytoin in the emergency department. Author(s): Comes J. Source: The Western Journal of Medicine. 1998 March; 168(3): 185. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9549420

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Fosphenytoin. Author(s): Luer MS. Source: Neurological Research. 1998 March; 20(2): 178-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9522355

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Fosphenytoin. Pharmacoeconomic implications of therapy. Author(s): Holliday SM, Benfield P, Plosker GL. Source: Pharmacoeconomics. 1998 December; 14(6): 685-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10346419

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Fosphenytoin: an intravenous option for the management of acute trigeminal neuralgia crisis. Author(s): Cheshire WP. Source: Journal of Pain and Symptom Management. 2001 June; 21(6): 506-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11397609

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Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. Author(s): Fischer JH, Patel TV, Fischer PA. Source: Clinical Pharmacokinetics. 2003; 42(1): 33-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489978

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Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses. Author(s): Pryor FM, Gidal B, Ramsay RE, DeToledo J, Morgan RO. Source: Epilepsia. 2001 February; 42(2): 245-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240597

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Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Author(s): Aynacioglu AS, Brockmoller J, Bauer S, Sachse C, Guzelbey P, Ongen Z, Nacak M, Roots I. Source: British Journal of Clinical Pharmacology. 1999 September; 48(3): 409-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10510154

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Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Author(s): Ninomiya H, Mamiya K, Matsuo S, Ieiri I, Higuchi S, Tashiro N. Source: Therapeutic Drug Monitoring. 2000 April; 22(2): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10774639

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Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Author(s): Odani A, Hashimoto Y, Otsuki Y, Uwai Y, Hattori H, Furusho K, Inui K. Source: Clinical Pharmacology and Therapeutics. 1997 September; 62(3): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9333104

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Genotoxicity of the anticonvulsant drug phenytoin (PHT): a follow-up study of PHTuntreated epileptic patients. I. Sister chromatid exchange (SCE) analysis. Author(s): Kaul A, Goyle S. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1999; 19(1): 61-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10321411

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Genotoxicity of the anticonvulsant drug phenytoin (PHT): a follow-up study of PHTuntreated epileptic patients. II. Mitotic index (MI) and proliferation kinetics. Author(s): Kaul A, Goyle S. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1999; 19(1): 73-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10321412

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Glucuronidation of prodrug reactive site: isolation and characterization of oxymethylglucuronide metabolite of fosphenytoin. Author(s): Annesley TM, Kurzyniec S, Nordblom GD, Buchanan N, Pool W, Reily M, Talaat R, Roberts WL. Source: Clinical Chemistry. 2001 May; 47(5): 910-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11325896

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Guidelines for nonemergency use of parenteral phenytoin products: proceedings of an expert panel consensus process. Panel on Nonemergency Use of Parenteral Phenytoin Products. Author(s): Meek PD, Davis SN, Collins DM, Gidal BE, Rutecki PA, Burstein AH, Fischer JH, Leppik IE, Ramsay RE. Source: Archives of Internal Medicine. 1999 December 13-27; 159(22): 2639-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10597754

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Gynaecomastia in association with phenytoin and zonisamide in a patient having a CYP2C subfamily mutation. Author(s): Ikeda A, Hattori H, Odani A, Kimura J, Shibasaki H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1998 November; 65(5): 803-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9810971

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Hair analysis for pharmaceutical drugs. I. Effective extraction and determination of phenobarbital, phenytoin and their major metabolites in rat and human hair. Author(s): Saisho K, Tanaka E, Nakahara Y. Source: Biological & Pharmaceutical Bulletin. 2001 January; 24(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11201247

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Hazards of doubling phenytoin dose in the face of an unrecognized interaction with ciprofloxacin. Author(s): Pollak PT, Slayter KL. Source: The Annals of Pharmacotherapy. 1997 January; 31(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8997469

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Heavy proteinuria, podocyte hypertrophy and severe systemic manifestations in a patient on phenytoin therapy. Author(s): Messiaen TG, Plaisier EM, Rossert J, Mougenot B, Bakouche P, Ronco PM. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1997 December; 12(12): 2723-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9430880

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Homocyst(e)ine levels in patients on phenytoin therapy. Author(s): James GK, Jones MW, Pudek MR. Source: Clinical Biochemistry. 1997 December; 30(8): 647-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9455620

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How high can we go with phenytoin? Author(s): Kozer E, Parvez S, Minassian BA, Kobayashi J, Verjee Z, Koren G. Source: Therapeutic Drug Monitoring. 2002 June; 24(3): 386-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021630

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How to give phenytoin safely. Report from a long-term care facility in North Carolina. Author(s): Pulliam C, Pait L, Winslow J. Source: N C Med J. 1996 September-October; 57(5): 292-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8854693

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Human CYP2C-mediated stereoselective phenytoin hydroxylation in Japanese: difference in chiral preference of CYP2C9 and CYP2C19. Author(s): Yasumori T, Chen LS, Li QH, Ueda M, Tsuzuki T, Goldstein JA, Kato R, Yamazoe Y. Source: Biochemical Pharmacology. 1999 June 1; 57(11): 1297-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10230773

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Hyaluronidase treatment for intravenous phenytoin extravasation. Author(s): Sokol DK, Dahlmann A, Dunn DW. Source: Journal of Child Neurology. 1998 May; 13(5): 246-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9620019

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Hypocalcemia-like electrocardiographic changes after administration of intravenous fosphenytoin. Author(s): Keegan MT, Bondy LR, Blackshear JL, Lanier WL. Source: Mayo Clinic Proceedings. 2002 June; 77(6): 584-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12059129

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Hypoglycaemia induced by phenytoin treatment for partial status epilepticus. Author(s): Di Gennaro G, Quarato PP, Colazza GB, Mascia A, Mari F, Manfredi M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 September; 73(3): 349-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185185

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Hypothermia and phenytoin toxicity. Author(s): Newberger DS, Blyth SA. Source: Clinical Neuropharmacology. 2003 July-August; 26(4): 172-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897633

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Hypothermia and phenytoin toxicity: a case report. Author(s): Alhaj E, Alhaj N. Source: Clinical Neuropharmacology. 2001 July-August; 24(4): 239-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11479397

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Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Author(s): Kidd RS, Curry TB, Gallagher S, Edeki T, Blaisdell J, Goldstein JA. Source: Pharmacogenetics. 2001 December; 11(9): 803-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740344

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Identification of catalase in human livers as a factor that enhances phenytoin dihydroxy metabolite formation by human liver microsomes. Author(s): Komatsu T, Yamazaki H, Nakajima M, Yokoi T. Source: Biochemical Pharmacology. 2002 June 15; 63(12): 2081-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12110367

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II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients. Author(s): Kaul A, Kalla NR, Goyle S. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 2001; 21(2): 151-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11223892

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Images in clinical medicine. Gingival hyperplasia induced by phenytoin. Author(s): Sharma S, Dasroy SK. Source: The New England Journal of Medicine. 2000 February 3; 342(5): 325. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10655531

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Immunolocalizaiton of c-Myc and bcl-2 proto-oncogene products in gingival hyperplasia induced by nifedipine and phenytoin. Author(s): Saito K, Mori S, Tanda N, Sakamoto S. Source: J Periodontol. 2000 January; 71(1): 44-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695937

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In vivo binding characteristics of phenytoin to serum proteins in monotherapy for adults with epilepsy. Author(s): Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y. Source: American Journal of Therapeutics. 2000 November; 7(6): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11304643

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In vivo binding characteristics of phenytoin to serum proteins in monotherapy pediatric patients with epilepsy. Author(s): Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Itokazu N, Sugimoto T. Source: Int J Clin Pharmacol Ther. 2000 January; 38(1): 25-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667833

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Inappropriate fosphenytoin use in the ED. Author(s): Johnson J, Wrenn K. Source: The American Journal of Emergency Medicine. 2001 July; 19(4): 293-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11447516

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Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin. Author(s): Coplin WM, Rhoney DH, Lyons EA, Murry KR. Source: Neurology. 1999 October 22; 53(7): 1611-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534289

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Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin. Author(s): O'Brien TJ, Cascino GD, So EL, Hanna DR. Source: Neurology. 1998 October; 51(4): 1034-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781525

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Incidence of intravenous site reactions in neurotrauma patients receiving valproate or phenytoin. Author(s): Anderson GD, Lin Y, Temkin NR, Fischer JH, Winn HR. Source: The Annals of Pharmacotherapy. 2000 June; 34(6): 697-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10860128

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Incidence of phenytoin induced gingival overgrowth in epileptic children: a six month evaluation. Author(s): Prasad VN, Chawla HS, Goyal A, Gauba K, Singhi P. Source: J Indian Soc Pedod Prev Dent. 2002 June; 20(2): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435021

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Influence of phenytoin on the disposition of irinotecan: a case report. Author(s): Murry DJ, Cherrick I, Salama V, Berg S, Bernstein M, Kuttesch N, Blaney SM. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 February; 24(2): 130-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990699

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Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors. Author(s): Nelson MH, Birnbaum AK, Remmel RP. Source: Epilepsy Research. 2001 April; 44(1): 71-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11255075

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Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Author(s): Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, Lee SS, Oh SW, Kim SW, Flockhart DA. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 October; 30(10): 1102-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12228186

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Interaction between phenytoin and ciprofloxacin. Author(s): Otero MJ, Moran D, Valverde MP. Source: The Annals of Pharmacotherapy. 1999 February; 33(2): 251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084426

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Interpatient and intrapatient variability in phenytoin protein binding. Author(s): Banh HL, Burton ME, Sperling MR. Source: Therapeutic Drug Monitoring. 2002 June; 24(3): 379-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021629

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Intravenous fosphenytoin in acute mania. Author(s): Applebaum J, Levine J, Belmaker RH. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 408-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716241

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Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, doubleblinded, placebo-controlled, crossover study. Author(s): McCleane GJ. Source: Anesthesia and Analgesia. 1999 October; 89(4): 985-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10512276

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Intravenous phenytoin: cheap but not necessarily a bargain. Author(s): Browne TR. Source: Neurology. 1998 October; 51(4): 942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781509

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Jiedu tongbi tang plus phenytoin sodium for severe acute sciatica. Author(s): Wang D. Source: J Tradit Chin Med. 2003 December; 23(4): 260. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719291

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Lack of pharmacokinetic drug interactions between tiagabine and carbamazepine or phenytoin. Author(s): Gustavson LE, Cato A 3rd, Boellner SW, Cao GX, Qian JX, Guenther HJ, Sommerville KW. Source: American Journal of Therapeutics. 1998 January; 5(1): 9-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099032

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Lack of pharmacokinetic interaction between grapefruit juice and phenytoin in healthy male volunteers and epileptic patients. Author(s): Kumar N, Garg SK, Prabhakar S. Source: Methods Find Exp Clin Pharmacol. 1999 November; 21(9): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10669910

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Lack of pharmacokinetic interaction between lansoprazole and intravenously administered phenytoin. Author(s): Karol MD, Locke CS, Cavanaugh JH. Source: Journal of Clinical Pharmacology. 1999 December; 39(12): 1283-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586395

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Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy. Author(s): Kaminow L, Schimschock JR, Hammer AE, Vuong A. Source: Epilepsy & Behavior : E&B. 2003 December; 4(6): 659-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698699

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Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin. Author(s): Steiner TJ, Dellaportas CI, Findley LJ, Gross M, Gibberd FB, Perkin GD, Park DM, Abbott R. Source: Epilepsia. 1999 May; 40(5): 601-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10386529

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Limited value of the urinary phenytoin metabolic ratio for the assessment of cytochrome P4502C9 activity in vivo. Author(s): Tassaneeyakul W, Birkett DJ, Pass MC, Miners JO. Source: British Journal of Clinical Pharmacology. 1996 December; 42(6): 774-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8971435

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Long-term anticonvulsant therapy leads to low bone mineral density--evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Author(s): Feldkamp J, Becker A, Witte OW, Scharff D, Scherbaum WA. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2000; 108(1): 37-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10768830

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Magnesium sulphate or phenytoin for prevention of eclampsia. Author(s): Amy JJ. Source: Natl Med J India. 1996 September-October; 9(5): 223-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8937062

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Magnesium sulphate versus phenytoin for eclampsia. Author(s): Cochrane Database Syst Rev. 2001;(4):CD000173 Source: Cochrane Database Syst Rev. 2000; (2): Cd000128. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687070

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Mathematical models to calculate fosphenytoin concentrations in the presence of phenytoin using phenytoin immunoassays and alkaline phosphatase. Author(s): Dasgupta A, Handy BC, Datta P. Source: American Journal of Clinical Pathology. 2000 January; 113(1): 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631861

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Mephenytoin overdose--phenytoin poisoning incognito? Case report and mephenytoin/phenytoin comparison. Author(s): Buchwald AL. Source: Journal of Toxicology. Clinical Toxicology. 2000; 38(7): 781-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11192466

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Metabolism of phenytoin by the gingiva of normal humans: the possible role of reactive metabolites of phenytoin in the initiation of gingival hyperplasia. Author(s): Zhou LX, Pihlstrom B, Hardwick JP, Park SS, Wrighton SA, Holtzman JL. Source: Clinical Pharmacology and Therapeutics. 1996 August; 60(2): 191-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8823237

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Metabolite and matrix interference in phenytoin immunoassays. Author(s): Rainey PM, Rogers KE, Roberts WL. Source: Clinical Chemistry. 1996 October; 42(10): 1645-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8855149

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Microdialysis sampling of carbamazepine, phenytoin and phenobarbital in subcutaneous extracellular fluid and subdural cerebrospinal fluid in humans: an in vitro and in vivo study of adsorption to the sampling device. Author(s): Lindberger M, Tomson T, Lars S. Source: Pharmacology & Toxicology. 2002 October; 91(4): 158-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12530465

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Modulation of androgen metabolism by phenytoin, oestradiol and tamoxifen in human gingival fibroblasts. Author(s): Soory M, Tilakaratne A. Source: Journal of Clinical Periodontology. 2003 June; 30(6): 556-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12795795

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Monitoring albumin levels in phenytoin therapy. Author(s): Crowder KM. Source: The Nurse Practitioner. 2000 April; 25(4): 18, 20, 126. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10790795

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Monitoring of phenytoin in human breast milk, maternal plasma and cord blood plasma by solid-phase extraction and liquid chromatography. Author(s): Shimoyama R, Ohkubo T, Sugawara K, Ogasawara T, Ozaki T, Kagiya A, Saito Y. Source: Journal of Pharmaceutical and Biomedical Analysis. 1998 August; 17(4-5): 863-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9682171

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More on fosphenytoin (Cerebyx) dosing. Author(s): Pruitt AC. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 1998 February; 24(1): 6-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9534521

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Mutual interaction between remacemide hydrochloride and phenytoin. Author(s): Leach JP, Girvan J, Jamieson V, Jones T, Richens A, Brodie MJ. Source: Epilepsy Research. 1997 January; 26(2): 381-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9095400

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My mother recently had a stroke and was put on Dilantin (phenytoin) to prevent seizures. I've heard Dilantin can interfere with coordination and the ability to think clearly. Is there an alternative drug? Author(s): Devinsky O. Source: Health News. 2000 November; 6(11): 10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11100687

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Myofibroblasts in phenytoin-induced hyperplastic connective tissue in the rat and in human gingival overgrowth. Author(s): Dill RE, Iacopino AM. Source: J Periodontol. 1997 April; 68(4): 375-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9150043

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Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin. Author(s): Curry WJ, Kulling DL. Source: American Family Physician. 1998 February 1; 57(3): 513-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9475899

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No gender effect on binding characteristics of phenytoin to serum proteins in monotherapy for adult patients with epilepsy. Author(s): Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y. Source: American Journal of Therapeutics. 2000 September; 7(5): 285-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317172

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Noncompliance leading to drug accumulation resulting in phenytoin toxicity. Author(s): Akula R, Hasan S, Pipalla R, Ferguson C. Source: Journal of the National Medical Association. 2003 December; 95(12): 1201-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717477

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Non-steady state population kinetics of intravenous phenytoin. Author(s): Frame B, Beal SL. Source: Therapeutic Drug Monitoring. 1998 August; 20(4): 408-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9712466

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Optimization of phenytoin therapy in adults with epilepsy in the Western Cape, South Africa. Author(s): Valodia PN, Seymour MA, Kies BM, Folb PI. Source: Journal of Clinical Pharmacy and Therapeutics. 1999 October; 24(5): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10583702

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Optimized high-performance liquid chromatographic method for determination of lamotrigine in serum with concomitant determination of phenytoin, carbamazepine, and carbamazepine epoxide. Author(s): Lensmeyer GL, Gidal BE, Wiebe DA. Source: Therapeutic Drug Monitoring. 1997 June; 19(3): 292-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9200770

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Oral tegafur/folinic acid chemotherapy decreases phenytoin efficacy. Author(s): Veldhorst-Janssen NM, Boersma HH, de Krom MC, van Rijswijk RE. Source: British Journal of Cancer. 2004 February 9; 90(3): 745. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760393

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Osteogenic actions of phenytoin in human bone cells are mediated in part by TGFbeta 1. Author(s): Nakade O, Baylink DJ, Lau KH. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1996 December; 11(12): 1880-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8970889

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Oxaprozin and 5-(p-hydroxyphenyl)-5-phenylhydantoin interference in phenytoin immunoassays. Author(s): Datta P. Source: Clinical Chemistry. 1997 August; 43(8 Pt 1): 1468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9267337

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Paradoxical seizures in phenytoin toxicity. Author(s): Chua HC, Venketasubramanian N, Tan CB, Tjia H. Source: Singapore Med J. 1999 April; 40(4): 276-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487084

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Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus. Author(s): Ogutu BR, Newton CR, Muchohi SN, Otieno GO, Edwards G, Watkins WM, Kokwaro GO. Source: British Journal of Clinical Pharmacology. 2003 July; 56(1): 112-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848783

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Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease. Author(s): Aweeka FT, Gottwald MD, Gambertoglio JG, Wright TL, Boyer TD, Pollock AS, Eldon MA, Kugler AR, Alldredge BK. Source: Epilepsia. 1999 June; 40(6): 777-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10368078

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Phenobarbital compared with phenytoin for the treatment of neonatal seizures. Author(s): Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, Paneth N, Minnigh B, Alvin J. Source: The New England Journal of Medicine. 1999 August 12; 341(7): 485-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10441604

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Phenytoin and carbamazepine cross reactivity: report of a case and review of literature. Author(s): Misra UK, Kalita J, Rathore C. Source: Postgraduate Medical Journal. 2003 December; 79(938): 703-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707249

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Phenytoin and fosphenytoin: a model of cost and clinical outcomes. Author(s): Armstrong EP, Sauer KA, Downey MJ. Source: Pharmacotherapy. 1999 July; 19(7): 844-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417033

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Phenytoin and phenobarbital inhibit human HERG potassium channels. Author(s): Danielsson BR, Lansdell K, Patmore L, Tomson T. Source: Epilepsy Research. 2003 June-July; 55(1-2): 147-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948624

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Phenytoin and phenobarbital stable isotope studies in neonates. Author(s): Malik SI, Painter MJ, Venkataramanan R, Alvin JD. Source: Pediatric Neurology. 2003 November; 29(5): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684232

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Phenytoin as a liquid material for embolisation of tumours. Author(s): Kasuya H, Shimizu T, Sasahara A, Takakura K. Source: Neuroradiology. 1999 May; 41(5): 320-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10379586

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Phenytoin dosage adjustment in Saudi epileptics: utilization of steady-state pharmacokinetic parameters. Author(s): Abduljabbar M, Al-Khamis K, Ogunniyi A, Daif AK, Al-Yamani M. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 1999 May; 6(3): 331-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210914

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Phenytoin for the prevention of motion sickness. Author(s): Albert EG. Source: The Medical Journal of Australia. 2003 June 2; 178(11): 575-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765507

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Phenytoin in cutaneous medicine: its uses, mechanisms and side effects. Author(s): Scheinfeld N. Source: Dermatology Online Journal [electronic Resource]. 2003 August; 9(3): 6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952753

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Phenytoin metabolism to 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) in man, cat and rat in vitro and in vivo, and susceptibility to phenytoin-induced gingival overgrowth. Author(s): Kamali F, Ball DE, McLaughlin WS, Seymour RA. Source: Journal of Periodontal Research. 1999 April; 34(3): 145-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10384402

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Phenytoin overview--metabolite interference in some immunoassays could be clinically important: results of a College of American Pathologists study. Author(s): Soldin SJ, Wang E, Verjee Z, Elin RJ; College of American Pathologists. Source: Archives of Pathology & Laboratory Medicine. 2003 December; 127(12): 1623-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632564

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Phenytoin toxicity due to fluoropyrimidines (5FU/capecitabine): three case reports. Author(s): Brickell K, Porter D, Thompson P. Source: British Journal of Cancer. 2003 August 18; 89(4): 615-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915866

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Phenytoin-diazepam interaction. Author(s): Murphy A, Wilbur K. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 659-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12708941

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Phenytoin-induced linear IgA dermatosis mimicking toxic epidermal necrolysis. Author(s): Tran D, Kossard S, Shumack S. Source: The Australasian Journal of Dermatology. 2003 November; 44(4): 284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616498

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Plasma total phenytoin: a possibly misleading test in developing countries. Author(s): Fedler C, Stewart MJ. Source: Therapeutic Drug Monitoring. 1999 April; 21(2): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10217333

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Population pharmacokinetics of tirilazad: effects of weight, gender, concomitant phenytoin, and subarachnoid hemorrhage. Author(s): Fleishaker JC, Fiedler-Kelly J, Grasela TH. Source: Pharmaceutical Research. 1999 April; 16(4): 575-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227715

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Pronounced palatal and mandibular tori observed in a patient with chronic phenytoin therapy: a case report. Author(s): Sasaki H, Ikedo D, Kataoka M, Kido J, Kitamura S, Nagata T. Source: J Periodontol. 1999 April; 70(4): 445-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10328658

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Randomized evaluation of adverse events and length-of-stay with routine emergency department use of phenytoin or fosphenytoin. Author(s): Coplin WM, Rhoney DH, Rebuck JA, Clements EA, Cochran MS, O'Neil BJ. Source: Neurological Research. 2002 December; 24(8): 842-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12500711

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Rapacuronium administration to patients receiving phenytoin or carbamazepine. Author(s): Tobias JD, Johnson JO. Source: Journal of Neurosurgical Anesthesiology. 2001 July; 13(3): 240-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11426100

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Rapid i.v. loading with phenytoin with subsequent dose adaptation using nonsteady-state serum levels and a Bayesian forecasting computer program to predict maintenance doses. Author(s): Martinelli EF, Muhlebach SF. Source: Journal of Clinical Pharmacy and Therapeutics. 2003 October; 28(5): 385-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632963

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Rapid in vitro conversion of fosphenytoin into phenytoin in sera of patients with liver disease: role of alkaline phosphatase. Author(s): Dasgupta A, Schlette E. Source: Journal of Clinical Laboratory Analysis. 2001; 15(5): 244-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574952

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Reactions to fosphenytoin editorial and review article. Author(s): Paloucek FP. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 February 15; 54(4): 449. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043575

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Reactions to fosphenytoin editorial and review article. Author(s): Hopefl A. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 February 15; 54(4): 445. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043574

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Reactions to fosphenytoin editorial and review article. Author(s): Orr J. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 February 15; 54(4): 442, 445. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043573

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Reactions to fosphenytoin editorial and review article. Author(s): Collette DR, Cramer RL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 February 15; 54(4): 442. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043572

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Reactions to fosphenytoin editorial and review article. Author(s): Matheson C. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 February 15; 54(4): 441-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043571

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Refractory idiopathic absence status epilepticus: A probable paradoxical effect of phenytoin and carbamazepine. Author(s): Osorio I, Reed RC, Peltzer JN. Source: Epilepsia. 2000 July; 41(7): 887-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10897162

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Relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin, quinidine, and theophylline to human tissues in vitro. Author(s): Bailey DN. Source: Journal of Analytical Toxicology. 1997 January-February; 21(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9013284

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Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine. Author(s): Giancarlo GM, Venkatakrishnan K, Granda BW, von Moltke LL, Greenblatt DJ. Source: European Journal of Clinical Pharmacology. 2001 April; 57(1): 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11372587

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Reversible panhypogammaglobulinemia associated with phenytoin treatment. Author(s): Pereira LF, Sanchez JF. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(10): 785-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477340

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Reversible total IgA deficiency associated with phenytoin treatment. Author(s): Braconier JH. Source: Scandinavian Journal of Infectious Diseases. 1999; 31(5): 515-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10576137

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Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia. Author(s): Anderson GD, Pak C, Doane KW, Griffy KG, Temkin NR, Wilensky AJ, Winn HR. Source: The Annals of Pharmacotherapy. 1997 March; 31(3): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9066931

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Risk of seizures from concomitant use of ciprofloxacin and phenytoin in patients with epilepsy. Author(s): Springuel P. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1998 January 13; 158(1): 104-5, 108-9. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9475922

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Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Author(s): Tennis P, Stern RS. Source: Neurology. 1997 August; 49(2): 542-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9270593

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Rocuronium-induced neuromuscular blockade is affected by chronic phenytoin therapy. Author(s): Hernandez-Palazon J, Tortosa JA, Martinez-Lage JF, Perez-Ayala M. Source: Journal of Neurosurgical Anesthesiology. 2001 April; 13(2): 79-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11294462

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Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Author(s): Swamy SM, Tan P, Zhu YZ, Lu J, Achuth HN, Moochhala S. Source: Biochemical and Biophysical Research Communications. 2004 February 13; 314(3): 661-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14741686

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Role of phenytoin in wound healing--a wound pharmacology perspective. Author(s): Talas G, Brown RA, McGrouther DA. Source: Biochemical Pharmacology. 1999 May 15; 57(10): 1085-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11265677

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Sensitive methods for determination of free digitoxin concentration using digitoxin immunoassays: demonstration of elevated free digitoxin concentration caused by digitoxin-phenytoin interaction by applying these new techniques. Author(s): Dasgupta A, Vega AE, Wells A, Datta P. Source: Therapeutic Drug Monitoring. 1999 December; 21(6): 625-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10604823

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Serum phenytoin concentration and IgG antibody titre to periodontal bacteria in patients with phenytoin-induced gingival overgrowth. Author(s): Yamada H, Nishimura F, Furuno K, Naruishi K, Kobayashi Y, Takashiba S, Murayama Y. Source: J Int Acad Periodontol. 2001 April; 3(2): 42-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666977

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Serum phenytoin levels of patients on gastrostomy tube feeding. Author(s): Faraji B, Yu PP. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1998 February; 30(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9604823

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Serum protein binding kinetics of phenytoin in monotherapy patients. Author(s): Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y. Source: Journal of Clinical Pharmacy and Therapeutics. 1998 October; 23(5): 361-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9875684

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Serum trace elements, glutathione, copper/zinc superoxide dismutase, and lipid peroxidation in epileptic patients with phenytoin or carbamazepine monotherapy. Author(s): Liu CS, Wu HM, Kao SH, Wei YH. Source: Clinical Neuropharmacology. 1998 January-February; 21(1): 62-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579288

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Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction. Author(s): Lardizabal DV, Luders HO, Hovinga CA, Bourgeois BF. Source: Neurology. 2004 January 13; 62(1): 161; Author Reply 161. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727316

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Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction. Author(s): Privitera MD, Welty T. Source: Neurology. 2004 January 13; 62(1): 161; Author Reply 161. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718732

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Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction. Author(s): Citerio G, Nobili A, Airoldi L, Pastorelli R, Patruno A. Source: Neurology. 2003 April 22; 60(8): 1395-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707459

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Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Author(s): Brandolese R, Scordo MG, Spina E, Gusella M, Padrini R. Source: Clinical Pharmacology and Therapeutics. 2001 October; 70(4): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673755

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Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. Author(s): Haltiner AM, Newell DW, Temkin NR, Dikmen SS, Winn HR. Source: Journal of Neurosurgery. 1999 October; 91(4): 588-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10507379

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Significant reduction of sertraline plasma levels by carbamazepine and phenytoin. Author(s): Pihlsgard M, Eliasson E. Source: European Journal of Clinical Pharmacology. 2002 February; 57(12): 915-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936714

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Significant removal of phenytoin during high flux dialysis with cellulose triacetate dialyzer. Author(s): Frenchie D, Bastani B. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998 March; 13(3): 817-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9550689

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Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine epoxide in human plasma by high-performance liquid chromatography with ultraviolet detection. Author(s): Bhatti MM, Hanson GD, Schultz L. Source: Journal of Pharmaceutical and Biomedical Analysis. 1998 March; 16(7): 1233-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9571541

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Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy. Author(s): Khafaga YM, Jamshed A, Allam AA, Mourad WA, Ezzat A, Al Eisa A, Gray AJ, Schultz H. Source: Acta Oncologica (Stockholm, Sweden). 1999; 38(1): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10090698

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Subacute cutaneous lupus erythematosus associated with phenytoin. Author(s): Ross S, Ormerod AD, Roberts C, Dwyer C, Herriot R. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 474-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372089

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Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial. Author(s): Ellis AJ, Wendon JA, Williams R. Source: Hepatology (Baltimore, Md.). 2000 September; 32(3): 536-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10960446

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Successful treatment with gabapentin in the presence of hypersensitivity syndrome to phenytoin and carbamazepine: a report of three cases. Author(s): Hamer HM, Morris HH. Source: Seizure : the Journal of the British Epilepsy Association. 1999 May; 8(3): 190-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10356381

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Sudden asystole during craniotomy: unrecognized phenytoin toxicity. Author(s): Berry JM, Kowalski A, Fletcher SA. Source: Journal of Neurosurgical Anesthesiology. 1999 January; 11(1): 42-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890385

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Synergistic effect of valproate coadministration and hypoalbuminemia on the serumfree phenytoin concentration in patients with severe motor and intellectual disabilities. Author(s): Mamiya K, Yukawa E, Matsumoto T, Aita C, Goto S. Source: Clinical Neuropharmacology. 2002 July-August; 25(4): 230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151911

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Systemic vasculitis associated with long-term phenytoin therapy. Author(s): Holt P. Source: N Z Med J. 1999 March 26; 112(1084): 100. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210297

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Task-related EEG and ERP changes without performance impairment following a single dose of phenytoin. Author(s): Chung SS, McEvoy LK, Smith ME, Gevins A, Meador K, Laxer KD. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 June; 113(6): 806-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048040

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Temperature effect on serum protein binding kinetics of phenytoin in monotherapy patients with epilepsy. Author(s): Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y. Source: European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. 1999 May; 47(3): 2958. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10382115

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The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Author(s): van der Weide J, Steijns LS, van Weelden MJ, de Haan K. Source: Pharmacogenetics. 2001 June; 11(4): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434505

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The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. Author(s): Wong YW, Yeh C, Thyrum PT. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 89-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11199955

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The effects of folic acid application on IL-1beta levels of human gingival fibroblasts stimulated by phenytoin and TNFalpha in vitro: a preliminary study. Author(s): Dogan A, Tunca Y, Ozdemir A, Sengul A, Imirzalioglu N. Source: J Oral Sci. 2001 December; 43(4): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11848192

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The effects of human mast-cell products and of phenytoin on androgen 5alphareductase expression in human gingival fibroblasts. Author(s): Soory M, Suchak A. Source: Archives of Oral Biology. 2001 September; 46(9): 847-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11420057

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The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels. Author(s): Kerb R, Aynacioglu AS, Brockmoller J, Schlagenhaufer R, Bauer S, Szekeres T, Hamwi A, Fritzer-Szekeres M, Baumgartner C, Ongen HZ, Guzelbey P, Roots I, Brinkmann U. Source: The Pharmacogenomics Journal. 2001; 1(3): 204-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11908757

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The subgingival microflora in phenytoin-induced gingival hyperplasia. Author(s): Takada K, Sugiyama H, Umezawa K, Mega J, Hirasawa M. Source: Journal of Periodontal Research. 2003 October; 38(5): 477-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941071

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Three Michaelis-Menten pharmacokinetic dosing methods compared with physician dosing of phenytoin in an outpatient neurology practice. Author(s): Spruill WJ, Wade WE, Cobb HH 3rd, Akbari S. Source: Pharmacotherapy. 2001 November; 21(11): 1407-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11714214

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Tiagabine versus phenytoin and carbamazepine as add-on therapies: effects on abilities, adjustment, and mood. Author(s): Dodrill CB, Arnett JL, Deaton R, Lenz GT, Sommerville KW. Source: Epilepsy Research. 2000 December; 42(2-3): 123-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074185

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Time course of lamotrigine de-induction: impact of step-wise withdrawal of carbamazepine or phenytoin. Author(s): Anderson GD, Gidal BE, Messenheimer JA, Gilliam FG. Source: Epilepsy Research. 2002 May; 49(3): 211-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076842

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Topical phenytoin in diabetic ulcers: a double blind controlled trial. Author(s): Pai MR, Sitaraman N, Kotian MS. Source: Indian Journal of Medical Sciences. 2001 November; 55(11): 593-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508631

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Topical phenytoin treatment of stage II decubitus ulcers in the elderly. Author(s): Rhodes RS, Heyneman CA, Culbertson VL, Wilson SE, Phatak HM. Source: The Annals of Pharmacotherapy. 2001 June; 35(6): 675-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408983

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Topical phenytoin versus EUSOL in the treatment of non-malignant chronic leg ulcers. Author(s): Carneiro PM, Nyawawa ET. Source: East Afr Med J. 2003 March; 80(3): 124-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12762426

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Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Author(s): Sachdeo RC, Sachdeo SK, Levy RH, Streeter AJ, Bishop FE, Kunze KL, Mather GG, Roskos LK, Shen DD, Thummel KE, Trager WF, Curtin CR, Doose DR, Gisclon LG, Bialer M. Source: Epilepsia. 2002 July; 43(7): 691-6. Erratum In: Epilepsia 2002 October; 43(10): 1273. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102670

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Total percentage body weight changes during add-on therapy with tiagabine, carbamazepine and phenytoin. Author(s): Hogan RE, Bertrand ME, Deaton RL, Sommerville KW. Source: Epilepsy Research. 2000 August; 41(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10924865

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Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Phenytoin or paraldehyde as the second drug for convulsions in children. Author(s): Townend W, Mackway-Jones K. Source: Emergency Medicine Journal : Emj. 2002 January; 19(1): 50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777879

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Toxic epidermal necrolysis after phenytoin usage in a brain trauma patient. Author(s): Schummer W, Schummer C, Kuwert C. Source: Journal of Neurosurgical Anesthesiology. 2002 July; 14(3): 229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172297

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Toxicity associated with a prolonged half-life of phenytoin in a 97-year-old woman: bezoar formation? Case report and clinical pathological conference. Author(s): Freedman MD, Sencil SK. Source: American Journal of Therapeutics. 1997 September-October; 4(9-10): 327-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10423627

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Treatment of phenytoin toxicity by the molecular adsorbents recirculating system (MARS). Author(s): Sen S, Ratnaraj N, Davies NA, Mookerjee RP, Cooper CE, Patsalos PN, Williams R, Jalan R. Source: Epilepsia. 2003 February; 44(2): 265-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558586

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Unexpected suppression of free phenytoin concentration by salicylate in uremic sera due to the presence of inhibitors: MALDI mass spectrometric determination of molecular weight range of inhibitors. Author(s): Biddle DA, Wells A, Dasgupta A. Source: Life Sciences. 2000; 66(2): 143-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10666010

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Up-regulation of keratinocyte growth factor and receptor: a possible mechanism of action of phenytoin in wound healing. Author(s): Das SJ, Olsen I. Source: Biochemical and Biophysical Research Communications. 2001 April 13; 282(4): 875-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352631

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Use of alkaline phosphatase to correct the underestimation of fosphenytoin concentration in serum measured by phenytoin immunoassays. Author(s): Dasgupta A, Warner BF, Datta P. Source: American Journal of Clinical Pathology. 1999 April; 111(4): 557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191778

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Use of biperiden hydrochloride in a child with severe dyskinesia induced by phenytoin. Author(s): Caksen H, Odabas D, Anlar O. Source: Journal of Child Neurology. 2003 July; 18(7): 494-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940655

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Use of topical phenytoin for wound care. Author(s): Johnson TJ. Source: S D J Med. 1998 October; 51(10): 387-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9803165

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Validated high performance liquid chromatographic method for simultaneous determination of phenytoin, phenobarbital and carbamazepine in human serum. Author(s): Kishore P, Rajnarayana K, Reddy MS, Sagar JV, Krishna DR. Source: Arzneimittel-Forschung. 2003; 53(11): 763-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677371

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Validation of population pharmacokinetic parameters of phenytoin using the parallel Michaelis-Menten and first-order elimination model. Author(s): Valodia PN, Seymour MA, McFadyen ML, Miller R, Folb PI. Source: Therapeutic Drug Monitoring. 2000 June; 22(3): 313-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10850399

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Valproate metabolites in high-dose valproate plus phenytoin therapy. Author(s): Sugimoto T, Muro H, Woo M, Nishida N, Murakami K. Source: Epilepsia. 1996 December; 37(12): 1200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8956852

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Variability in the bioavailability of phenytoin capsules in males and females. Author(s): Meyer MC, Straughn AB, Mhatre RM, Shah VP, Chen ML, Williams RL, Lesko LJ. Source: Pharmaceutical Research. 2001 March; 18(3): 394-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442282

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Variability of total phenytoin serum concentrations within elderly nursing home residents. Author(s): Birnbaum A, Hardie NA, Leppik IE, Conway JM, Bowers SE, Lackner T, Graves NM. Source: Neurology. 2003 February 25; 60(4): 555-9. Erratum In: Neurology. 2003 May 27; 60(10): 1727. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601091

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Vecuronium sensitivity in part due to acute use of phenytoin. Author(s): Gronert GA. Source: Anesthesiology. 2002 October; 97(4): 1035; Author Reply 1035. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357188

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Vestibular and hearing manifestations of phenytoin toxicity: a retrospective series. Author(s): De Diego JI, Prim MP, Marcos S, De Sarria MJ, Arpa J, Gavilan J. Source: Ear, Nose, & Throat Journal. 2001 June; 80(6): 404, 407-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11433844

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Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability. Author(s): Gatti G, Bartoli A, Marchiselli R, Michelucci R, Tassinari CA, Pisani F, Zaccara G, Timmings P, Richens A, Perucca E. Source: British Journal of Clinical Pharmacology. 1993 December; 36(6): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959280

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When the face tells the tale. Course facial features caused by phenytoin use. Author(s): Mishriki YY. Source: Postgraduate Medicine. 1998 March; 103(3): 49-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9519029

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

Finding Nutrition Studies on Phenytoin 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 “phenytoin” (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 “phenytoin” (or a synonym): •

Use of phenytoin to treat digitalis-induced cardiac arrhythmias in a miniature Shetland pony. Author(s): Veterinary Pharmacy, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.152, 3508 TD Utrecht (Netherlands) Source: Wijnberg, I.D. Kolk, J.H. van der Hiddink, E.G. Veterinary-Record (United Kingdom). (1999). volume 144(10) page 259-261.

Additional physician-oriented references include: •

A comparison of extracellular levels of phenytoin in amygdala and hippocampus of kindled and non-kindled rats. Author(s): Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany. Source: Potschka, Heidrun Loscher, Wolfgang Neuroreport. 2002 January 21; 13(1): 16771 0959-4965

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Anticonvulsant and psychomotor activity of nitrendipine alone and in combination with phenytoin and valproate in rats. Author(s): Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Source: Balakrishnan, S Bhargava, V K Pandhi, P Methods-Find-Exp-Clin-Pharmacol. 1999 Jul-August; 21(6): 441-7 0379-0355

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Complexation of phenytoin with some hydrophilic cyclodextrins: effect on aqueous solubility, dissolution rate, and anticonvulsant activity in mice. Author(s): Dipartimento Farmaco-Chimico, Facolta di Farmacia, Universita degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy. Source: Latrofa, A Trapani, G Franco, M Serra, M Muggironi, M Fanizzi, F P Cutrignelli, A Liso, G Eur-J-Pharm-Biopharm. 2001 July; 52(1): 65-73 0939-6411

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Decreases in phenytoin hydroxylation activities catalyzed by liver microsomal cytochrome P450 enzymes in phenytoin-treated rats. Author(s): Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan. [email protected] Source: Yamazaki, H Komatsu, T Takemoto, K Saeki, M Minami, Y Kawaguchi, Y Shimada, N Nakajima, M Yokoi, T Drug-Metab-Dispos. 2001 April; 29(4 Pt 1): 427-34 0090-9556

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Effect of melatonin and phenytoin on an intracortical ferric chloride model of posttraumatic seizures in rats. Author(s): Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India. Source: Srivastava, A K Gupta, S K Jain, S Gupta, Y K Methods-Find-Exp-ClinPharmacol. 2002 April; 24(3): 145-9 0379-0355

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Effect of 'Mentat' on the pharmacokinetics of single and multiple doses o phenytoin in rabbits. Author(s): Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India. Source: Garg, S K Islam, A S KuMarch, N Sehgal, M Bhargava, V K Neurol-India. 1999 June; 47(2): 104-7 0028-3886

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Effect of sugar-modified beta-cyclodextrins on dissolution and absorption characteristics of phenytoin. Author(s): Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Osaka, Japan. Source: Tanino, T Ogiso, T Iwaki, M Biol-Pharm-Bull. 1999 March; 22(3): 298-304 09186158

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Female gonadal sex steroids potentiate the anti-convulsant activity of phenytoin sodium. Author(s): Department of Pharmacology and Pharmacotherapeutics, J. N. Medical College, Belgaum, India. Source: Kankanwadi, S K Patil, P A Indian-J-Exp-Biol. 1998 July; 36(7): 713-5 0019-5189

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Induction of tirilazad clearance by phenytoin. Author(s): Clinical Pharmacokinetics Unit, Pharmacia and Upjohn, Inc, Kalamazoo, MI 49007, USA. [email protected] Source: Fleishaker, J C Pearson, L K Peters, G R Biopharm-Drug-Dispos. 1998 March; 19(2): 91-6 0142-2782

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Influence of phenytoin and valproate on thalamocortical evoked potentials and their paired-pulse potentiation. Author(s): Institute of Physiology, Czechoslovak Academy of Sciences, Prague. Source: Mares, P Pohl, M Koryntova, H Physiol-Res. 1992; 41(6): 475-8 0862-8408

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Interactions between folate metabolism, phenytoin metabolism, and liver microsomal cytochrome P450. Source: Billings, R E Drug-Nutr-Interact. 1984; 3(1): 21-32 0272-3530

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Mechanisms of neurotransmission of valproate sodium in suppressing barbiturate and phenytoin withdrawal syndrome. Author(s): University of Medicine, Department of Pharmacology and Medicinal Toxicology, Plovdiv, Bulgaria. Source: Peichev, L Folia-Med-(Plovdiv). 1992; 34(2): 14-9 0204-8043

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Neurotoxic damage of granule cells in the dentate gyrus and the cerebellum and cognitive deficit following neonatal administration of phenytoin in mice. Author(s): Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. Source: Ogura, H Yasuda, M Nakamura, S Yamashita, H Mikoshiba, K Ohmori, H JNeuropathol-Exp-Neurol. 2002 November; 61(11): 956-67 0022-3069

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Phenytoin alters Purkinje cell axon morphology and targeting in vitro. Author(s): Department of Neuropathology, University of Freiburg, Germany. Source: Tauer, U Knoth, R Volk, B Acta-Neuropathol-(Berl). 1998 June; 95(6): 583-91 0001-6322

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Phenytoin alters the disposition of topotecan and N-desmethyl topotecan in a patient with medulloblastoma. Author(s): Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. Source: Zamboni, W C Gajjar, A J Heideman, R L Beijnen, J H Rosing, H Houghton, P J Stewart, C F Clin-Cancer-Res. 1998 March; 4(3): 783-9 1078-0432

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Phenytoin hypersensitivity syndrome. Author(s): Department of Dermatology, Ankara Numune Hospital, Ankara, Turkey. Source: Gungor, E Alli, N Comoglu, S Comcuoglu, C Neurol-Sci. 2001 June; 22(3): 261-5 1590-1874

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Phenytoin intoxication induced by fluvoxamine. Author(s): Hizen National Hospital, Saga, Japan. Source: Mamiya, K Kojima, K Yukawa, E Higuchi, S Ieiri, I Ninomiya, H Tashiro, N Ther-Drug-Monit. 2001 February; 23(1): 75-7 0163-4356

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Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Author(s): Clinical Pharmacology Unit, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel. [email protected] Source: Caraco, Y Muszkat, M Wood, A J Pharmacogenetics. 2001 October; 11(7): 587-96 0960-314X

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Phenytoin toxicity as a result of 5-fluorouracil administration. Author(s): Hutt Hospital, Lower Hutt, New Zealand. Source: Rosemergy, I Findlay, M N-Z-Med-J. 2002 August 9; 115(1159): U124 1175-8716

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Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures. Author(s): Division of Statistics and Operational Research, Department of Mathematical Sciences, University of Liverpool, Mathematics & Oceanography Building, Peach Street, Liverpool, UK, L69 7ZL. [email protected] Source: Tudur, S Marson, A G Williamson, P R Cochrane-Database-Syst-Revolume 2001; (4): CD001769 1469-493X

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Phenytoin-induced choreoathetosis in patients with severe myoclonic epilepsy in infancy. Author(s): Department of Pediatrics, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. [email protected] Source: Saito, Y Oguni, H Awaya, Y Hayashi, K Osawa, M Neuropediatrics. 2001 October; 32(5): 231-5 0174-304X

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Probable metabolic interaction of doxifluridine with phenytoin. Author(s): Department of Hospital Pharmacy, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan. [email protected] Source: Konishi, H Morita, K Minouchi, T Nakajima, M Matsuda, M Yamaji, A AnnPharmacother. 2002 May; 36(5): 831-4 1060-0280

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Suppression of experimental barbiturate and phenytoin withdrawal syndrome using valproate sodium. Author(s): Department of Pharmacology and Drug Toxicology, University of Medicine, Plovdiv, Bulgaria. Source: Peichev, L Folia-Med-(Plovdiv). 1992; 34(3-4): 3-7 0204-8043

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The effect of chronic phenytoin treatment on tissue folate concentrations and on the activities of the methyl synthetic enzymes in the rat [Anticonvulsants, folacin, folic acid]. Source: Carl, G.F. Smith, D.B. J-Indian-Chem-Soc. Calcutta : The Society. July 1983. volume 60 (7) page 2368-2374. 0019-4522

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The Effect of diphenylhydantoin (phenytoin) on the sequential stages of intestinal folate absorption. Source: Nelson, Edward W. Crick, William F. Cerda, James J. Wilder, B.J. Streiff, Richard R. Drug-Nutrient-Interact. New York : Alan R. Liss, Inc. 1983. volume 2 (1) page 47-56. ill., charts. 0272-3530

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The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Source: Bano, G. Amla, V. Raina, R.K. Zutshi, U. Chopra, C.L. Plant-Med-J-Med-PlantRes. Stuttgart, W. Ger. : Georg Thieme Verlag. 1987. volume 53 (6) page 568-569. 00320943

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The effect of sucralfate on the steady-state serum concentrations of phenytoin. Author(s): Veterans Administration Medical Centre, Tucson, AZ 85723. Source: Malli, R Jones, W N Rindone, J P Labadie, E L Drug-Metabol-Drug-Interact. 1989; 7(4): 287-93 0792-5077

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Unbound plasma phenytoin concentrations measured using enzyme immunoassay technique on the cobas MIRA analyser--in vivo effect of valproic acid. Author(s): Department of Clinical Pharmacology, Queen Elizabeth Hospital, Woodville South, South Australia. Source: Sallustio, B C Morris, R G Ther-Drug-Monit. 1992 February; 14(1): 9-13 0163-4356

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vitamins Folic Acid Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Pyridoxine Alternative names: Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Riboflavin Alternative names: Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 (Cobalamin) Alternative names: Cobalamin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B2 (Riboflavin) Alternative names: Riboflavin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 (Pyridoxine) Alternative names: Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Alternative names: Calciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com

Nutrition

Vitamin K Alternative names: Menadione Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com •

Minerals Biotin Source: Integrative Medicine Communications; www.drkoop.com Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Folate Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Vitamin H (Biotin) Alternative names: Biotin Source: Integrative Medicine Communications; www.drkoop.com

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CHAPTER 3. CLINICAL TRIALS AND PHENYTOIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning phenytoin.

Recent Trials on Phenytoin The following is a list of recent trials dedicated to phenytoin.5 Further information on a trial is available at the Web site indicated. •

Effect of Ginkgo Biloba on Phenytoin Elimination Condition(s): Healthy Study Status: This study is completed. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will examine how the herbal remedy ginkgo biloba may affect the body's elimination of other medicines. Many people take ginkgo biloba to improve memory, mental alertness and overall feeling of well being. Since this product is considered a food supplement and not a drug, it is not subject to the rigorous premarket testing required for prescription and over-the-counter (OTC) drugs. As a result, information has not been collected on possible interactions between ginkgo biloba and other medications. This study will look at how ginkgo biloba affects the elimination of phenytoin-a medication used to treat patients with seizures. Normal healthy volunteers 21 years of age or older may be eligible for this 40-day study. Candidates will provide a medical history and undergo a physical examination and routine blood tests. Women of childbearing age must use a reliable form of birth control other than oral contraceptives ("the pill"). For at least 2 weeks before the study and throughout its duration, study participants may not have any of the following: 1) medications that can affect platelet function (e.g., aspirin, Motrin, Advil, Nuprin, ibuprofen, etc.); 2) alcoholic beverages; 3) grapefruit and grapefruit juice; and 4) all medications except those given by study personnel. On day 1 of the study, subjects take one 500-mg dose of phenytoin at 8:00 A.M. On an empty stomach. (Subjects fast the night before taking the phenytoin and are

5

These are listed at www.ClinicalTrials.gov.

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allowed to eat breakfast 2 hours after the dose). Blood samples are drawn just before dosing and again at 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 hours after the dose. Blood drawn on this first study day is collected through a catheter (small plastic tube) placed in a vein to avoid multiple needlesticks. After the 12-hour sample is collected, the subject goes home and then returns to the clinic for the remaining blood draws, which are taken by direct needlestick. When the blood sampling is completed, subjects begin ginkgo therapy. The NIH Clinical Center provides participants a supply of 60-mg capsules of ginkgo to take twice a day (at 8 A.M. and 8 P.M.) for 4 weeks. At the end of the 4 weeks, subjects are given a second dose of phenytoin as described above and repeat the blood sampling procedure. Subjects continue taking ginkgo during this second phenytoin study. Phase(s): Phase I; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011063 •

Effects of Phenytoin on Cocaine Use in Humans - 2 Condition(s): Cocaine-Related Disorders Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Minnesota Purpose - Excerpt: To determine the effects of phenytoin on the self-administration of smoked cocaine. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000285

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

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

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•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 4. PATENTS ON PHENYTOIN 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.6 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 “phenytoin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on phenytoin, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Phenytoin By performing a patent search focusing on phenytoin, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 6Adapted

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

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

Composition containing silver ammonium phenytoin complex and a phenytoin and use of said composition Inventor(s): Lasker; Sigmund E. (New York Medical College, Valhalla, NY 10595) Assignee(s): None Reported Patent Number: 5,571,521 Date filed: February 13, 1995 Abstract: Compositions containing silver ammonium phenytoin complex and a phenytoin are usefully employed, particularly when applied topically, for the treatment of animal or human tissue, for wound healing and are useful in wound dressing preparations for the prevention or treatment of infections. The compositions are usefully applied by direct topical application to the wound or tissue to be treated or may be directly applied to the wound or tissue or incorporated in or coated on a dressing, such as a bandage. Excerpt(s): Phenytoin, its derivatives, and compositions containing the same are well known in the art, see U.S. Pat. Nos. 2,409,754; 3,932,449; 3,798,233; 4,093,809, the disclosures of which are incorporated herein. While many uses for phenytoin and its derivatives are disclosed in these patents, it is apparent that phenytoin and its derivatives have not been employed as biocides. Organometallic compounds have been employed as specific biocides, particularly as antimicrobials. For example, organometallic derivatives of sulfadiazine are among the most prominent of these materials. see U.S. Pat. Nos. 3,761,590; 4,020,150; 4,049,802; 3,792,161; and 4,078,058, in which organometallic compounds of sulfadiazine are disclosed, such as silver sulfadiazine, zinc sulfadiazine, and cerium sulfadiazine. While each of these compounds exhibits satisfactory effect in particular applications, no single one of these compounds, or class of these compounds, is effective against a broad range of infections and infective agents such as bacteria, viruses, plasmodia, and the like. Additionally, treatment of certain microbial infections with metallic compounds or complexes of sulfadiazine has resulted in the development of resistant microbial strains. Hence, it is an object of this invention to provide compositions useful as a versatile biocide for the treatment of infections, such as infections caused by bacteria, viruses and plasmodia. Web site: http://www.delphion.com/details?pn=US05571521__

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Crystalline sodium phenytoin monohydrate Inventor(s): Bosch; Robert Lee (Allendale, MI), Johnson; Peter Raymond (West Lafayette, IN), Stahl; Robert Joseph (Holland, MI) Assignee(s): Warner-lambert Company (morris Plains, Nj) Patent Number: 6,245,917 Date filed: May 3, 1999 Abstract: Crystalline sodium phenytoin monohydrate is stable, nonhygroscopic, and water soluble.

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Excerpt(s): This invention relates to a crystalline form of sodium phenytoin monohydrate, to pharmaceutical formulations containing the same, and to methods for preparing and using the substance. Phenytoin is the generic name for 5,5-diphenyl-2,4imidazolidinedione. It also is known as diphenylhydantoin. It is used extensively to treat convulsive disorders such as epilepsy. Because phenytoin is poorly soluble in aqueous mixtures, it cannot be effectively used in injectable solutions, or even in solid preparations for oral use. The compound generally is utilized as a sodium salt, which is readily soluble in water. However, even sodium phenytoin anhydrate rapidly dissociates into phenytoin, which then precipitates from aqueous solutions, thereby making uniform dosing difficult. Moreover, commercial production of sodium phenytoin anhydrate results in complex mixtures of polymorphic forms of the product, and the individual polymorphs exhibit different aqueous solubilities and dissolution rates, thereby further exacerbating dosing irregularities. To date, there has been no single crystal form of any phenytoin sodium capable of analysis by x-ray diffraction. An object of this invention is to provide a new chemical substance that is a crystalline form of a monohydrate of sodium phenytoin. The new compound can be crystallized into a single crystal form which can readily be analyzed by x-ray diffraction. The sodium phenytoin monohydrate crystal form of this invention is stable for prolonged periods of time, and it exhibits excellent aqueous solubility characteristics, thereby allowing for improved uniformity of dosing. The new chemical compound is readily formulated for both oral and parenteral administration to humans for treatment of epilepsy and other convulsive disorders. Web site: http://www.delphion.com/details?pn=US06245917__ •

Fluorimetric immunoassay for diphenylhydantoin Inventor(s): McGregor; Adrienne R. (London, GB), Smith; David S. (London, GB) Assignee(s): Technicon Instruments Corporation (tarrytown, Ny) Patent Number: 4,160,818 Date filed: April 12, 1977 Abstract: Substituted hydantoin drugs (for example phenytoin) and tricyclic antidepressant drugs (for example nortriptyline) are assayed by mixing them with a fluorescent labelled compound and antibodies, and measuring the fluorescence of the mixture. The assay does not necessitate any separation step and may be effected by continuous-flow techniques. Excerpt(s): This invention is concerned with immunoassays and, more particularly, with a method of assaying diphenylhydantoin and nortriptyline, and similar drugs in biological fluid samples, such as blood serum for example. It is well established that the optimum therapeutic level of diphenylhydantoin (hereinafter "DPH") in blood (serum) is approximately 10.mu.g/ml. Lower levels will usually fail to control seizures, while at higher levels, undesirable side effects become evident. For example, nystagmus (involuntary rapid movement of the eyes) sets in at approximately 20.mu.g/ml, ataxia (failure of muscualr co-ordination) at approximately 30.mu.g/ml, and mental changes above about 40.mu.g/ml. Because of the narrow safe therapeutic range, it is general practice to monitor the blood levels of patients receiving DPH. The most commonly applied assay for DPH at the present time is gas-liquid chromatography. Successive extraction steps followed by an evaporation step are necessary to isolate the drug from the serum sample before injection into a gas-liquid chromatograph and measurement of the peak corresponding to DPH on the resulting chromatogram. The extraction,

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evaporation and chromatography steps are all time-consuming and difficult to automate. Therefore, the sample throughput of this method is low. Comparatively large samples are required (typically 1 ml of serum) which can be a disadvantage, for example in pediatric practice. Web site: http://www.delphion.com/details?pn=US04160818__ •

Labeled hydantoin conjugate and its use in analytical element and immunoassays Inventor(s): Danielson; Susan J. (Rochester, NY), Olyslager; Robert J. (Rochester, NY), Sundberg; Michael W. (Penfield, NY) Assignee(s): Eastman Kodak Company (rochester, Ny) Patent Number: 4,752,568 Date filed: January 13, 1986 Abstract: A heterogeneous, competitive binding immunoassay for either phenytoin or phenobarbital is conducted with a labeled conjugate comprising a derivative of hydantoin and a label. The hydantoin derivative is 5-ethyl,5-phenyl hydantoin and it is linked to the label (e.g. an enzyme) with a linkage derived from an aliphatic monocarboxylic acid. The immunoassay can be carried out either in solution or with a dry analytical element. Excerpt(s): This invention relates to clinical chemistry and to a heterogeneous, competitive binding immunoassay for the determination of either phenytoin or phenobarbital. This invention is particularly useful for the determination of these drugs in aqueous liquids, such as biological fluids. Competitive binding immunoassays, which take advantage of natural immunological reactions, have found widespread use as analytical techniques in clinical chemistry. Because of the specificity of the reactions, they are particularly advantageous in quantifying biological analytes which are present in very low concentration and cannot be adequately quantitated by chemical techniques. Such analytes include, for example, therapeutic drugs, narcotics, enzymes, hormones, proteins, etc. In competitive binding assays, a labeled analyte is placed in competition with unlabeled analyte for reaction with a fixed amount of the appropriate antibody. Unknown concentrations of the analyte can be determined from the measured signal of either the bound or unbound (i.e. free) labeled analyte. Web site: http://www.delphion.com/details?pn=US04752568__

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Method for screening of potential anti-epileptic drugs using a Drosophila melanogaster model Inventor(s): Kumar; Sushil (Lucknow, IN), Sharma; Abhay (Lucknow, IN) Assignee(s): Council of Scientific and Industrial Research (new Delhi, In) Patent Number: 6,291,739 Date filed: March 24, 2000 Abstract: The invention relates to a method for screening anti-epileptic drugs using fruit fly Drosophila melanogaster by generating single and double mutant lines of K.sup.+ channel genes in Drosophila melanogaster, culturing mutant lines on Drosophila medium under standard conditions, identifying the mutants, separating male flies under ether anesthesia, supplying the mutant males with medium containing each of

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the four antiepileptic drugs, phenobarbital, phenytoin, carbaamazepine and valproate, separately, administering ether anesthesia to the drug treated flies and examining their leg shaking intensity under stereomicroscope, observing the antiepileptic effect in the drug treated males wherein a reduced intensity of leg shaking, compared to leg shaking in normally fed etherized males, is indicative of antiepileptic activity in the drug. Excerpt(s): The present invention relates to a method for the screening of anti-epileptic drugs using an animal model. More particularly, the present invention relates to a method for the screening of anti-epileptic drugs using neurological mutants of the fruit fly Drosophila melanogaster. By studying the effect of various established anti-epileptic drugs (AEDs) on neuronal hyperexcitability phenotype of these mutants, the applicants demonstrate that animal models, particularly fruit fly could serve as a simple, rapid and inexpensive whole organism in vivo phenotype-based model for screening of drugs, compounds, natural products etc. for anti-epileptic-like activities. The development of an animal model and the associated process for neuroactive drug screening is of immense value in the development and identification of drugs and their potential for treatment of neurological disorders such as epilepsy. Epilepsy refers to a collection of disorders affecting 1-2 % of the global population. It is a brain disorder characterized by recurrent seizures, brief changes in behaviour caused by disordered, synchronous and rhythmic firing of populations of neurons in the central nervous system. Epilepsies are caused both by genetic factors and by cortical damage. They have been classified into more than 40 distinct types on the basis of characteristic symptoms and signs, cause, seizure types, electroencephalographic patterns and age of onset. The single common feature of epilepsy syndromes is a persistent increase of neuronal excitability that occasionally and unpredictably results in a seizure. With the identification of mutations in genes encoding voltage- and ligand- gated ion channels as molecular aetiology of some forms of inherited human epilepsy, and with the understanding of altered synapse function as the causal factor in epilepsies caused by cortical damage, it has been learnt that the common mechanisms underlying the hyperexcitability in diverse forms of epilepsy is alteration of intrinsic properties of neurons and/or synaptic function (McNamara, 1999, Nature 399: A15-A22; Puranam and McNamara, 1999, Curr. Op. Neurobiol. 9: 281-287; Steinlein, 1998, Clin. Genet. 54: 169-175). Web site: http://www.delphion.com/details?pn=US06291739__ •

Method of treating motion sickness with anticonvulsants and antitussive agents Inventor(s): Chelen; William (4396 Laclamen Dr., Centerville, OH 45459) Assignee(s): None Reported Patent Number: 5,234,929 Date filed: July 20, 1992 Abstract: A method of treating or preventing motion sickness is disclosed which comprises administering an anti-motion sickness effective amount of an anticonvulsant compound such as phenytoin, ethotoin, primidone, ethosuximide or carbamazepine, in combination with a potentiating amount of an antitussive or cough suppressant agent such as dextromethorphan, levopropoxyphene, muscaphene, pholocodeine, or carbetapentene. The antitussive compounds of the present invention act as potentiating agents so as to enable effective treatment or prevention of motion sickness using a reduced amount of the anticonvulsant compound normally used in such treatment. The method of the present invention reduces the potential for various side effects and thus

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provides a safer and more effective method of treatment for motion sickness than prior art methods. Excerpt(s): The invention relates in general to the prevention or treatment of motion sickness, and in particular to the prevention or treatment of motion sickness through the use of antitussives as potentiating agents in combination with anticonvulsant compounds. In the treatment of motion sickness, traditional remedies have relied predominately upon drugs in the antihistaminic and anticholinergic drug classes. See e.g. Money, Psychological Reviews, 50(1):1-39(1970); Wood et al., Aerospace Med. 43(3):249-252(1972); and Wood et al., Aviation Environ Med. 58(9 Supp.): A262-5(1987). Examples of these drugs include promethazine, scopolamine, dimenhydrinate, and cyclazine, and sometimes these compounds are combined with a sympathomimetic agent such as ephedrine or amphetamine to enhance their action and to reduce the side effects such as lethargy or drowsiness that often accompany the use of these drugs. Other side effects that often accompany the drugs used in the prevention of motion sickness have been blurred vision, dizziness, dryness of mouth and sedation. Thus, therapies using the present day anti-motion sickness drugs, either alone or in combination with other drugs, have been less than optimal. More recently, it has been discovered that certain anticonvulsant agents are useful in methods to prevent or treat motion sickness. For example, in U.S. Pat. No. 4,992,443 (Chelen), a method of treating motion sickness is disclosed wherein the patient is administered an effective amount of a particular anticonvulsant compound such as diphenylhydantoin (or phenytoin), ethotoin, or primidone. Although these compounds avoid many of the problems present in the prior traditional methods for treating motion sickness, it is still a highly desirable object to reduce the amount of anticonvulsant that can effectively be administered to a patient to control motion sickness to a bare minimum so as to minimize or eliminate entirely the likelihood of side effects from the anticonvulsant compound. Web site: http://www.delphion.com/details?pn=US05234929__ •

Methods for treating neurodegenerative diseases and disorders using N-(2,6disubstituted aromatic)-N'-pyridinyl ureas and other anticonvulsant compounds Inventor(s): Taylor, Jr.; Charles Price (Chelsea, MI), Weber; Mark Lawrence (Farmington Hills, MI) Assignee(s): Warner-lambert Company (morris Plains, Nj) Patent Number: 6,133,299 Date filed: February 25, 1993 Abstract: The instant invention is novel uses of known N-(2,6-disubstituted phenyl)-N'3- and 4-pyridinyl ureas and pharmaceutically acceptable acid addition salts thereof. Such compounds as N-(2-chloro-6-methylphenyl)-N'-4-pyridinyl urea monohydrochloride or N-(2,3-dichlorophenyl)-N'-4-pyridinyl urea are used for treating neurodegenerative disorders, perinatal asphyxia, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. The instant invention is similar novel uses of known anticonvulsant compounds as ralitoline, phenytoin, lamotrigine, tetrodotoxin, lidocaine, and carbamazepine. Excerpt(s): The present invention relates to novel therapeutic uses of a known compound, N-(2,6-disubstituted aromatic)-N'-pyridinyl ureas, its derivatives, and pharmaceutically acceptable salts. The present invention also relates to novel therapeutic uses of various other anticonvulsant drugs, their derivatives, and

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pharmaceutically acceptable salts. The present invention concerns a method for treating neurodegenerative diseases and disorders in a mammal in need of such treatment. Such neurodegenerative diseases are, for example, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. The present invention also covers treating neurodegenerative disorders termed acute brain injury. These include but are not limited to: stroke, head trauma, and asphyxia. Web site: http://www.delphion.com/details?pn=US06133299__ •

Oral suspension of phenytoin Inventor(s): Loran; Muriel R. (New York, NY) Assignee(s): Pharmaceutical Associates, Inc. (tampa, Fl) Patent Number: 4,280,995 Date filed: December 31, 1979 Abstract: The invention comprises a 5,5-diphenyl-2,4-imidazolidinedione-guaran complex formed by reacting an aqueous solution of guaran with an organic solvent solution of 5,5-diphenyl-2,4-imidazolidinedione. The invention also includes a therapeutic composition and method wherein the active agent is the guaran 5,5diphenyl-2,4-imidazolidinedione complex. Excerpt(s): The present invention relates to a new compound comprising the reaction product of guaran and 5,5-deiphenyl-2,4-imidazolidinedione (phenytoin). Phenytoin, commonly known as dilantin, is 5,5-phenyl-2,4-imidazolidinedione and is a well known therapeutic agent useful as an anti-convulsant effective for the treatment of generalized tonic-clonic seizures ("grand mal") in adults and children, and is also useful in the treatment of simple and complex partial seizures ("focal" and "tempral lobe and psychomotor"). 5,5-diphenyl-2,4-imidazolidinedione and methods for its production are described in U.S. Pat. No. 2,409,754. The pharmacology of phenytoin in Anticonvulsants, Vida, Julius A. Ed. 176-284, Academic Press, New York, 1977. Web site: http://www.delphion.com/details?pn=US04280995__

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Parenteral phenytoin compositions Inventor(s): Kao; Shui-Hsi (Succasunna, NJ), Kay; Allen I. (Succasunna, NJ), Sampson; Karla (West Caldwell, NJ) Assignee(s): Warner-lambert Company (morris Plains, Nj) Patent Number: 4,696,814 Date filed: August 21, 1985 Abstract: Stable, aqueous solutions of phenytoin sodium can be made using polyvinylpyrrolidone with or without an alcoholic solvent system. Excerpt(s): Phenytoin is 5,5-diphenyl-2,4-imidazolidinedione. It is a well-known pharmaceutical agent having anticonvulsant and antiepileptic activity. Its preparation is described in U.S. Pat. No. 2,409,754. Due to phenytoin's poor solubility in water, phenytoin sodium is employed in the preparation of injectable solutions of the drug. In order to stabilize solutions of phenytoin sodium, it is conventional to employ aqueous alcoholic solvent systems. Such solvent systems generally contain propylene glycol

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and/or other alcohols. Even in the presence of alcoholic solvents, these solutions are unstable following dilution in intravenous fluids in that crystals form therein, precluding their safe use. Web site: http://www.delphion.com/details?pn=US04696814__ •

Parenteral phenytoin preparations Inventor(s): Fawzi; Mahdi B. (Flanders, NJ), Taylor; Anne K. (Morris Plains, NJ) Assignee(s): Warner-lambert Company (morris Plains, Nj) Patent Number: 4,642,316 Date filed: May 20, 1985 Abstract: Useful parenteral phenytoin preparations can be made using certain complexes of phenytoin or phenytoin sodium. Excerpt(s): Phenytoin is 5,5-diphenyl-2,4-imidazolidinedione. It is a well-known pharmaceutical agent having anticonvulsant and antiepileptic activity. Its preparation is described in U.S. Pat. No. 2,409,754. Due to phenytoin's poor solubility in water, phenytoin sodium, of empirical formula C.sub.15 H.sub.11 N.sub.2 NaO.sub.2, which is more soluble, is employed in the preparation of injectable solutions of the drug. In order to stabilize solutions of phenytoin sodium, it is conventional to employ aqueous alcoholic solvent systems. One conventional component of such systems, propylene glycol, has been associated with undesirable side effects. The need arose for stable aqueous preparations based on phenytoin which did not contain potentially dangerous solvents, e.g., propylene glycol. Web site: http://www.delphion.com/details?pn=US04642316__

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Phenytoin therapy Inventor(s): Ayer; Atul D. (Palo Alto, CA), Hatamkhany; Zahedeh (San Jose, CA), Laidlaw; Barbara F. (San Jose, CA), Shivanand; Padmaja (Mountain View, CA) Assignee(s): Alza Corporation (mountain View, Ca) Patent Number: 6,110,499 Date filed: July 20, 1998 Abstract: A therapeutic composition, a dosage form and a method are disclosed for administering phenytoin indicated for the management of epilepsy. Excerpt(s): This invention pertains to both a novel and useful dosage form comprising phenytoin for the management of epilepsies. The invention relates also to a therapeutic composition of matter comprising phenytoin and a solubility enhancing agent. The invention relates also to a process for increasing the solubility of phenytoin in a therapeutic phenytoin formulation. Additionally, the invention pertains to a method for producing antiepileptic therapy in a patient in need of antiepileptic phenytoin therapy over time. The term "epilepsies" is a collective designation for a group of central nervous system disorders having in common the repeated occurrence of sudden and transitory episodes of abnormal phenomena of motor, convulsive, sensory, autonomic or psychic origin. The seizures are nearly always correlated with abnormal and excessive discharges in the brain, which can be recorded by an electroencephalogram. Epilepsy is

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the most common neurological disorder. Epilepsy afflicts millions of people world wide, and it is more common in children than in adults. For the purposes of drug treatment, it is useful to classify patients according to the type of seizure the patient experiences. The generally accepted classification of epileptic seizure comprises partial seizures consisting of focal and local seizures, and generalized seizures consisting of convulsive or nonconvulsive seizures. Web site: http://www.delphion.com/details?pn=US06110499__ •

Reagents and methods for the rapid and quantitative assay of pharmacological agents Inventor(s): Cheng; Anthony K. (Anaheim, CA), Oh; Chan S. (Chino Hills, CA), Yan; Cheng F. (Irvine, CA) Assignee(s): Beckman Instruments, Inc. (fullerton, Ca) Patent Number: 5,747,352 Date filed: May 23, 1994 Abstract: Bidentate reagents for rapidly and quantitatively assaying the concentration of pharmacological agents in biological samples are described. The reagents are used in an immunoassay format for determining the concentration of desired, preselected pharmacological agents, such as benzoylecgonine, cocaine, an opiate, PCP, digoxigenin, acetaminophen, carbamazepine, phenytoin, primidone, theophylline, an aminoglycoside antibiotic, vancomycin, quinidine or a cannabinoid. Excerpt(s): The invention concerns reagents and methods for rapidly and quantitatively assaying the concentration of pharmacological agents in biological samples. More specifically, the invention concerns the formation and use of biotinylated bidentate reagents and immunoassay formats capable of determining the concentration of desired, preselected pharmacological agents, such as cocaine, acetaminophen or digoxin. The ability to assess whether an individual has been exposed to a pharmacological agent, and a capability of determining the concentration of such an agent in a biological sample is of broad importance in medicine, law enforcement and other areas. In particular, the medical and societal ramifications of substance abuse (cocaine, cannabinoids, opiates, etc.) has necessitated the development of assays capable of detecting such substances. Direct usage of cocaine has increased dramatically during the last decade (Rosenberg, N. M. et al., Amer. J. Dis. Child. 145:1430-1432 (1991)). Such usage has increased the prevalence of occult cocaine exposure in neonatals, young children and adolescents to levels approaching 5% in some urban areas of the United States (Rosenberg, N. M. et al., Amer. J. Dis. Child. 145:1430-1432 (1991)). Web site: http://www.delphion.com/details?pn=US05747352__

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Stable pharmaceutical composition of 3-(hydroxymethyl)-5,5-diphenylhydantoin disodium phosphate ester Inventor(s): Herbranson; Dale E. (Lindenhurst, IL), Rosenberg; Leonard S. (Flemington, NJ), Speicher; Earl R. (Buffalo Grove, IL) Assignee(s): E. I. DU Pont DE Nemours and Company (wilmington, De) Patent Number: 4,925,860 Date filed: May 25, 1989

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Abstract: Described is a stable pharmaceutical composition of 3-(hydroxymethyl-5,5diphenylhydantoin disodium phosphate ester, the prodrug of 5,5-diphenylhydantoin (phenytoin) a commonly used drug for the treatment and management of epilepsy and other types of convulsive states. It has been found that degradation of the prodrug to phenytoin can be controlled by controlling the pH of the composition. Controlling the pH to between 8.3 to 9.4 results in the production of diphenylglycinamide as the primary degradant and minimization of degradation to phenytoin. If the pH is maintained at a lower or higher value, then the degradation pattern changes, with earlier than expected product failure. Excerpt(s): 5,5-Diphenylhydantoin, phenytoin, is a commonly used drug for the treatment and management of epilepsy and other types of convulsive states. While phenytoin is widely used for the treatment of these conditions, it has an extremely low solubility and, consequently, low bioavailability. Phenytoin is a high melting, weakly acidic drug exhibiting poor solubility in water. These properties lead to erratic absorption after oral dosing with both the free acid and the sodium salt. See the papers by S. A. Varia et al., Journal of Pharmaceutical Sciences 73(8): 1068-190, August 1984. For parenteral use, sodium phenytoin is formulated in an aqueous alkaline medium of pH 12 containing 40% propylene glycol and 10% ethanol. The parenteral dosage form can be painful if the intravenous injection is rapid and the free acid appears to precipitate at intramuscular injection sites. Emergency use of parenteral phenytoin, namely, in cases of controlling seizures in patients with head injuries, may require the administration of the drug intramuscularly. To be clinically acceptable, intramuscular administration of a drug should cause minimal tissue damage at the injection site. Intramuscular administration of sodium phenytoin has been reported to be painful, probably due to the precipitation of phenytoin. It has also been shown to cause hemorrhage, hematoma and necrosis at the injection site in cats and rabbits. U.S. Pat. No. 4,260,769 issued Apr. 7, 1981, and the previously noted articles by S. A. Varia et al. in the Journal of Pharmaceutical Sciences, disclose various prodrugs of phenytoin with more desirable physicochemical properties. In particular, patent 4,260,769 and the noted publications disclose the phenytoin prodrug 3-(hydroxymethyl)-5,5diphenylhydantoin disodium phosphate ester which is shown to have physicochemical properties that are suitable for a prodrug of phenytoin for parenteral use. S. A. Varia and V. J. Stella, at pages 10871090 in the Journal of Pharmaceutical Sciences, report that the compound did not exhibit any tissue damage after subcutaneous or intramuscular administration and thus, would be a suitable prodrug candidate for intramuscular delivery of phenytoin. However, this prodrug tends to degrade with the subsequent precipitation of phenytoin. Common methods used to delay the precipitation point involve modifying the formulation to contain agents that might solubilize larger quantities of the degradation product. These agents include alcohol, propylene glycol, L-arginine, sodium desoxycholate, polysorbate-80, and various combinations of these compounds. It has been found that the prodrug, 3-(hydroxymethyl)-5,5-diphenylhydantoin disodium phosphate ester, is stable in an aqueous system when maintained at a pH of about 8.3 to 9.4 to produce diphenylglycinamide as the primary degradant with minimal quantities of phenytoin. A preferred pharmaceutical composition would contain 35 to 130 mg/mL of the prodrug and 0.05 to 0.2 M buffer. Web site: http://www.delphion.com/details?pn=US04925860__

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Sustained release pharmaceutical preparation Inventor(s): Beiman; Elliott (Morristown, NJ), Landsman; Fred (Princeton, NJ) Assignee(s): Cascade Development, Inc. a Subsidiary of Cardinal Health, Inc. (paradise Valley, Nv) Patent Number: 5,968,554 Date filed: July 7, 1998 Abstract: The present invention pertains to a sustained release drug delivery system hich comprises a core of active ingredient, an enteric coating, a second coating of active ingredient and lastly a readily gastric-soluble protective coating. The sustained release dosage form of this invention is useful for pharmaceutically active ingredients that have limited aqueous solubility, especially phenytoin sodium, and other pH dependent soluble drugs. Excerpt(s): This invention relates to sustained release pharmaceutical preparations and to a method for making them. The novel drug delivery system contains a core comprising the active pharmaceutical, an enteral coating over the core comprising a pH dependent water soluble polymer, a second coating of the active pharmaceutical, and thereafter a coating which is soluble in gastric juices. The drug delivery system of the invention may be utilized with a wide variety of pharmaceutically active agents which have pH dependent solubilities to prepare sustained release compositions. This invention also relates to a novel method for preparing these drug delivery systems and to sustained release compositions made thereby. A sustained release dosage form may be defined as a preparation which releases a drug, in vivo, at a considerably slower rate than is the case from an equivalent dose of a conventional (non-sustained release) dosage form. The objective of employing a sustained release product is to obtain a satisfactory drug response while at the same time, reducing the frequency of administration. An example of a drug which is popularly used in a sustained release form is chlorpheniramine maleate. In conventional form, the drug may be given as 4 mg doses every four (4) hours or in sustained release form as 12 mg every twelve (12) hours. Sustained release compositions for the sequential or timed release of medicaments are well known in the art. Generally, such compositions contain medicament particles, normally administered in divided doses two (2) or three (3) times daily, mixed with or covered by a coating material which is resistant to degradation or disintegration in the stomach and/or in the intestine for a selected period of time. Release of the medicament may occur by leeching, erosion, rupture, diffusion or similar actions depending upon the nature and thickness of the coating material. Web site: http://www.delphion.com/details?pn=US05968554__

Patent Applications on Phenytoin As of December 2000, U.S. patent applications are open to public viewing.7 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 phenytoin:

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

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Compaction process for manufacture of sodium phenytoin dosage form Inventor(s): Crotts, George; (Kintnersville, PA), Fessehaie, Mebrahtu G.; (Mineola, NY), Gadiraju, Srinivas Raju; (Randolph, NJ), Gawel, John; (Clark, NJ), Ghebre-Sellassie, Isaac; (Morris Plains, NJ), Sheth, Ashlesh K.; (Randolph, NJ) Correspondence: Mehdi Ganjeizadeh; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030083360 Date filed: May 14, 2002 Abstract: A process for the roller compaction and manufacture of a pharmaceutical formulation comprises the steps of adding sodium phenytoin to a vessel of a blender and adding at least one excipient to the vessel. The mixture is blended and transferred to a roller compactor, where pressure is applied to the blend of sodium phenytoin and excipient. Next, the resultant compaction is milled to form a granulation, which is blended a second time and is suitable for further processing into a dosage form. Preferably, the excipients include magnesium stearate, sugar, lactose monohydrate, and talc. In an alternative embodiment, talc is added immediately prior to the granulation being blended for a second time. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/290,970, the entire contents of which are herein incorporated by reference. The present invention pertains to a method of manufacturing a dosage form of sodium phenytoin. In particular, the present invention pertains to a method of manufacturing an orally administered extended release sodium phenytoin capsules. In the pharmaceutical development art, a sustained release dosage form may be defined as a preparation which releases a drug, in vivo, at a considerably slower rate than is the case from an equivalent dose of a conventional (nonsustained release) dosage form. The objective of employing a sustained release product is to obtain a satisfactory drug response while at the same time, reducing the frequency of administration and maintaining bioequivalence to existing sodium phenytoin formulations. An example of a drug, which is popularly used in a sustained release form, is chlorpheniramine maleate. In conventional form, the drug may be given as 4 mg doses every 4 hours or in sustained release form as one dose of 12 mg every 12 hours. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compositions for prevention and alleviation of skin wrinkles Inventor(s): Ahn, Ho-Jeong; (Daejeon, KR), Kim, Moon-Moo; (Daejeon, KR), Kim, SangNyun; (Daejeon, KR), Lee, Hak-Mo; (Daejeon, KR), No, Kyung-Ok; (Chungbuk, KR) Correspondence: Albert Wai Kit Chan; Law Offices OF Albert Wai Kit Chan; World Plaza Suite 604; 141 07 20th Avenue; Whitestone; NY; 11357; US Patent Application Number: 20040052750 Date filed: June 19, 2003 Abstract: The present invention discloses a topical composition for prevention and alleviation of wrinkling which comprises one or two or more selected from the group consisting of Phenytoin, Valproic acid, Cyclosporin A, Nifedipine, Diltiazem, Verapamil HCl and Amoldipine as an active ingredient having an effect of boosting collagen synthesis.

Patents 99

Excerpt(s): The present invention relates to a topical composition for prevention and alleviation of skin wrinkles which comprises one or two or more selected from the group consisting of phenytoin, valproic acid, cyclosporine A, nifedipine, diltiazem, verapamil HCl and amoldipine as an active ingredient having an effect of promoting collagen synthesis, in conjunction with conventional components of a formulation for transdermal absorption such as cream, ointment, lotion, skin tonic, gel, pack, patch or patch-type administering apparatus. Skin aging is developed by both endogenous causes, for example, aging, and environmental causes. The effects of aging are shown as wrinkles in the skin, which include neck wrinkles, worry lines, frown lines, crow's feet, the folds from the side of the nose to the corners of the mouth, and fine lines around the eyes, below the lips, and over the face. Skin wrinkles caused by aging, though there are individual differences, commonly occur in individuals in their early twenties and increase with age. With aging, the amount of dermal collagen of skin is decreased and alterations in elastic fibers occur, whereby the skin relaxes and fine wrinkles appear. Meanwhile, collagen is a major matrix protein produced by fibroblasts of the skin, being present in the extracellular matrix. It is a primary protein comprising 30% by weight of proteins in the human body, and has a firm structure of a triple helix. It is known that collagen functions to provide structural stability to the skin, durability of connective tissues and cohesion of tissues while supporting cell coherence, cell proliferation, and induction of differentiation of unspecialized cells. Also, it is known that collagen is broken down by exposure to UV, an environmental cause of skin aging, and the damage by UV is proportional to the accumulated time of exposure thereto. UV denatures collagenous fibers, causing wrinkles and decreasing elasticity of the skin. Other environmental causes known to promote skin aging include wind, heat and smoking. As mentioned above, collagen is closely related with skin aging. The amount of collagen in the dermis is decreased with aging and by UV radiation. Collagen decreases by 65% from age 20 to age 80. Such a decrease of collagen makes the skin thin and further, is closely associated with the formation of skin wrinkles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microscale diffusion immunoassay Inventor(s): Hatch, Anson; (Seattle, WA), Kamholz, Andrew; (Seattle, WA), Weigl, Bernhard H.; (Seattle, WA), Yager, Paul; (Seattle, WA) Correspondence: Greenlee Winner And Sullivan P C; 5370 Manhattan Circle; Suite 201; Boulder; CO; 80303; US Patent Application Number: 20020090644 Date filed: February 14, 2000 Abstract: Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be

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measured in less than a minute. The assay is homogeneous, rapid, requires only microliter volumes of reagents and sample, and is applicable to a wide range of analytes, including therapeutic drugs, molecular biological markers, and environmental contaminants. Methods for separating particles of similar size in a diffusion separator are also provided. Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/135,417 filed May 21, 1999, which is incorporated by reference herein to the extent not inconsistent herewith. The immunoassay is the workhorse of analytical biochemistry. It allows the unique binding abilities of antibodies to be widely used in selective and sensitive measurement of small and large molecular analytes in complex samples. The driving force behind developing new immunological assays is the constant need for simpler, more rapid, and less expensive ways to analyze the components of complex sample mixtures. Current uses of immunoassays include therapeutic drug monitoring, screening for disease or infection with molecular markers, screening for toxic substances and illicit drugs, and monitoring for environmental contaminants. All publications referred to herein are hereby incorporated by reference in their entirety to the extent not inconsistent herewith. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

N-methoxymethyl-5,5-diphenylbarbituric acid Inventor(s): Gutman, Daniela; (Rishon Lezion, IL), Herzog, Hershel; (Tarrytown, NY) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030018080 Date filed: February 12, 2002 Abstract: A method of N-alkoxyalkylating ureides according to the invention comprises reacting a ureide of structure I 1with an alkylating agent of structure III 2in the presence of a basic catalyst in an aprotic reaction medium. The ureide may be a 5,5-disubstituted barbituric acid, or it may be phenytoin, glutethimide, and ethosuximide. The alkylating agent is an ester of a sulfonic acid. The base may be a hydride or amine. A preferred process comprises N-alkoxyalkylating 5,5-diphenyl-barbituric acid with methoxymethyl methanesulfonate in the presence of di-isopropyl ethyl amine and isolating the resultant N,N'-bismethoxymethyl-5,5-diphenyl-barb- ituric acid. The invention also contemplates the novel compounds N-methoxymethyl-5,5-diphenylbarbituric acid, N-methoxymethyl ethosuximide, and N-methoxymethyl glutethimide, and a method comprising administering them to a patient. Excerpt(s): The invention relates to a new means for N-alkylating ureides that is higher yielding, more convenient, and safer to use than techniques practiced heretofore. This approach is particularly suited to preparing N-(alkoxyalkylene) ureides, which include anti-convulsant drugs of the N-substituted barbituric acid class. U.S. Pat. No. 4,628,056 teaches a method of making 1,3 bis(methoxymethyl)-5,5-diphenyl barbituric acid (also called N,N'-bis(methoxymethyl)-5,5-diphenyl barbituric acid) by dissolving diphenyl barbituric acid in cooled dimethylformamide, adding sodium hydride, then adding chloromethyl methyl ether. Chloromethyl methyl ether has been widely used to alkylate with a methoxymethylene function. However, it is highly toxic and regulated as a carcinogen. It is extremely volatile and flammable under exothermic reaction conditions, and alternatives to its use are strongly desirable. Almost three decades ago,

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methoxymethyl methanesulfonate was identified as an agent for alkylating some alcohols and amines in a self-catalyzing reaction. Karger et al., J.A.C.S. 91:5663 (1969). With amines, the reaction was complex and led to salts, dimers, and other side products being formed. This method has not been applied to alkylation of ureides, or imides, for which there are major differences in electron availability at nitrogen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Phenytoin sodium pharmaceutical compositions Inventor(s): Addicks, William J.; (Mrogantown, WV), Benson, Kerry R.; (Morgantown, WV), Duda, Joseph P.; (Morgantown, WV), Snider, Daniel A.; (Morgantown, WV) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 555 13th Street, N.W.; Suite 701, East Tower; Washington; DC; 20004; US Patent Application Number: 20010043945 Date filed: May 11, 2001 Abstract: A pharmaceutical composition is provided containing an admixture of phenytoin sodium and an erodible matrix which extends the release of the phenytoin sodium over about a two hour period. The erodible matrix comprises binder(s) and diluent(s) which control the release of drug from the pharmaceutical composition. The erodible matrix can further comprise an alkaline pH modifier. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/255,705, filed Feb. 23, 1999. The invention relates generally to the field of epilepsy treatment, and more particularly to antiepileptic pharmaceutical compositions for oral administration. Phenytoin sodium is a known antiepileptic compound. Phenytoin, phenytoin sodium, and procedures for their manufacture are well known, see for example Kao et al U.S. Pat. No. 4,696,814 issued Sep. 29, 1987; Fawzi et al U.S. Pat. No. 4,642,316 issued Feb. 10, 1987; and Henze U.S. Pat. No. 2,409,754, issued Oct. 22, 1946, all of which are incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with phenytoin, 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 “phenytoin” (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 phenytoin. You can also use this procedure to view pending patent applications concerning phenytoin. 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 PHENYTOIN Overview This chapter provides bibliographic book references relating to phenytoin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on phenytoin 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 “phenytoin” (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 phenytoin: •

Prevention and Treatment Considerations for the Dental Patient With Special Needs Source: Academy of Dentistry for Persons with Disabilities, American Academy of Pediatric Dentistry. 199x. 89 p. Contact: Available from American Dental Hygienists' Association (ADHA). 444 North Michigan Avenue, Chicago, IL 60611. (800) 243-2342 or (312) 440-8900; Fax (312) 4408929; E-mail: [email protected]; http://www.adha.org. PRICE: $2.00 for booklet, $15.00 for slides (30-day rental only, plus $50.00 refundable deposit); nonmembers add 25 percent (Illinois residents add 8 percent sales tax). Order number 2933. Summary: This manual includes a basic discussion of prevention and treatment considerations for dental patients with special needs. Topics covered include quality of life; dietary considerations; plaque; periodontal disease; nursing-related caries (baby bottle tooth decay); the sugar content of medications; phenytoin (Dilantin); overretained teeth; bruxism; drooling; mastication, rumination, and pouching; mental

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retardation; the Down Syndrome pattern of tooth eruption; dental implications of cerebral palsy; orthodontic therapy; trauma; self-injurious behavior; physical and sexual abuse; restraint and management; supporting devices; toothbrushing, including positioning techniques; preventive agents; adaptive equipment; and psychosocial factors. The manual concludes with a glossary of terms for the use of non-dental professionals, a list of resources, and a bibliography. Black and white photographs illustrate many of the conditions discussed. 45 references.

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

A Remarkable Medicine Has Been Overlooked: Including an Autobiography and the Clinical Section of the Broad Range of Use of Phenytoin by Jack Dreyfus; ISBN: 0826410693; http://www.amazon.com/exec/obidos/ASIN/0826410693/icongroupinterna

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Epilepsy and the Oral Manifestations of Phenytoin Therapy (Monographs in Oral Science, Vol 9) by T.M Hassel, Thomas M. Hassell; ISBN: 380551008X; http://www.amazon.com/exec/obidos/ASIN/380551008X/icongroupinterna

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Fifty Years of Phenytoin (International Congress and Symposium Series, No 120) by M. Dam, A. Richens (Editor); ISBN: 0905958527; http://www.amazon.com/exec/obidos/ASIN/0905958527/icongroupinterna

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Phenytoin (Dilantin, Diphenylhydantoin) and its adverse effects in the human body; ISBN: 1559141212; http://www.amazon.com/exec/obidos/ASIN/1559141212/icongroupinterna

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Phenytoin-induced teratology and gingival pathology; ISBN: 0890044120; http://www.amazon.com/exec/obidos/ASIN/0890044120/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “phenytoin” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:8 8 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic

Books

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NTP technical report on perinatal toxicology and carcinogenesis studies of 5,5diphenylhydantoin (phenytoin) (cas no. 57-41-0) in F344. Author: N rates and B6C3F1 mice (feed studies) [microform] / National Toxicology Program; Year: 1993

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

Gingivitis and Periodontal Disease Source: in McDonald, R.E. and Avery, D.A., eds. Dentistry for the Child and Adolescent. 7th ed. St. Louis, MO: Mosby, Inc. 2000. p. 440-484. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $72.00 plus shipping and handling. ISBN: 0815190174. Summary: Gingivitis, a type of periodontal disease, is an inflammation involving only the gingival (gum) tissues next to the tooth. This chapter on gingivitis and periodontal disease is from a textbook on dentistry for the child and adolescent that is designed to help undergraduate dental students and postdoctoral pediatric dentistry students provide comprehensive oral health care for infants, children, teenagers, and individuals with various disabilities. The authors cover simple gingivitis, including eruption gingivitis, gingivitis associated with poor oral hygiene, and allergy and gingival inflammation; acute gingival disease, including that due to herpes simplex virus infection, recurrent aphthous ulcer (canker sore), acute necrotizing ulcerative gingivitis (ANUG), acute candidiasis (thrush, a fungal infection), and acute bacterial infections; chronic nonspecific gingivitis; chlorhexidine as a therapeutic plaque control agent; conditioned gingival enlargement, including puberty gingivitis, fibromatosis, and phenytoin (Dilantin) induced gingival overgrowth; scorbutic gingivitis (associated with vitamin C deficiency); periodontal diseases in children, including periodontitis, premature bone loss in primary dentition, Papillon Lefevre syndrome (precocious periodontosis), gingival recession, the differential diagnosis of self mutilation, abnormal frenum attachment, and frenectomy; the clinical assessment of oral cleanliness and periodontal disease; extrinsic stains and deposits on teeth; and dental calculus (seen with low frequency in children). 44 figures. 93 references.

database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Methods to Increase Poison Elimination Source: in Catto, G.R.D. New Clinical Applications-Nephrology: Drugs and the Kidney. Hingham, MA: Kluwer Academic Publishers. p. 65-111. 1990. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $54. ISBN: 0792389182. Summary: Most poisoned patients recover with little more than nursing care, but about 10 percent need intensive supportive therapy to maintain vital functions. Methods to increase the elimination of poisons are appropriate in less than 5 percent of the cases. Moreover, such techniques should only be undertaken by those experienced in their use, since the morbidity and mortality are otherwise likely to be higher than with supportive measures alone. This review details techniques currently available to increase poison elimination. These include: forced diuresis (excretion of poisons; indications; phenobarbitone; phenytoin; lithium); forced diuresis with pH manipulation (rationale; procedure of alkaline diuresis; procedure of acid diuresis; indications for alkaline and acid diuresis; forced alkaline diuresis (phenobarbitone, salicylate, and phenoxyacetate herbicide poisoning); forced acid diuresis (amphetamine, fenfluramine, phencyclidine, and quinine poisoning); complications); repeat-dose activated charcoal therapy (mechanism of action; factors affecting efficacy; the questionable co-use of cathartics; therapeutic value in treating various drug toxicities (e.g.: phenobarbitone, carbamazepine, salicylate, theophylline); dialysis (indications; peritoneal dialysis vs. hemodialysis; the value of dialysis in treating specific drug toxicities); and hemoperfusion (indications and contraindications; clinical considerations; efficacy; and use for treating specific drug toxicities). 148 references.

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Physical and Chemical Oral Injury Source: in Miller, R.L., et al. General and Oral Pathology for the Dental Hygienist. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 215-233. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail: [email protected]; http://www.mosby.com. PRICE: $43.00 plus shipping and handling. ISBN: 0801670241. Stock Number 07024. Summary: This chapter, from a textbook on pathology for dental hygiene students, presents a discussion of physical and chemical oral injury. Topics covered include factitial and iatrogenic injury; physical and chemical injury to teeth, including acute injury, chronic injury, resorption of teeth, and dental stains; physical and chemical injury to soft tissue, including denture-related reactive conditions; chemical injury, including chemical burns, phenytoin hyperplasia, amalgam tattoo, exogenous lingual pigmentation, allergic reactions, and cancer chemotherapy effects; and radiation injury, including radiation mucositis, bone necrosis and infection, and radiation xerostomia and caries. The chapter includes a list of learning objectives; illustrative case studies; and recommended readings. 30 figures.

•

Problems Related to the Prevention of Oral Disease Source: in Grundy, M.C.; Shaw, L.; and Hamilton, D.V. Illustrated Guide to Dental Care for the Medically Compromised Patient. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 111-122. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 432-

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1380; E-mail: [email protected]; http://www.mosby.com. PRICE: $24.95 plus shipping and handling. ISBN: 0815140223. Summary: This chapter, from an illustrated guide to dental care for medically compromised patients, discusses problems related to the prevention of oral disease. Topics covered include dietary related disorders, including obesity, anorexia nervosa and bulimia nervosa, dietary habits, carbohydrate metabolism, phenylketonuria, cystic fibrosis, chronic renal failure, and celiac disease; medication and caries; erosion of the dental tissues; preventive therapy, including prevention and control of dental caries, fissure sealants, prevention and control of periodontal disease, chemical plaque control, and involvement of the caregiver; drug-induced gingival hyperplasia, including that dependent on phenytoin, cyclosporin, and nifedipine; and self-mutilation, including Lesch-Nyhan syndrome, congenital insensitivity to pain, and gingivitis artefacta. For each condition, the authors provide a brief description, the components of medical management, and suggestions for dental care. Illustrations, including photographs, are included. 15 figures. 2 tables. •

Drug Monitoring Source: in Catto, G.R.D. New Clinical Applications-Nephrology: Drugs and the Kidney. Hingham, MA: Kluwer Academic Publishers. p. 113-151. 1990. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $54. ISBN: 0792389182. Summary: This review aims to cover aspects of drug monitoring with particular emphasis on the problems in patients with renal disease. Since an understanding of therapeutic drug monitoring requires a basic knowledge of drug disposition and pharmacokinetics, some important aspects of these topics are discussed first. Following consideration of therapeutic drug concentration monitoring, the final section of this review briefly discusses aspects of monitoring drugs by use of measurable pharmacodynamic end points. Topics include: the effect of renal disease on drug disposition and pharmacokinetics (absorption and bioavailability, distribution and protein binding, metabolism, excretion); the effect of renal disease on drug pharmacodynamics; and therapeutic drug monitoring (assay methods, individual drugs (digoxin, gentamicin, lithium, anticonvulsant drugs (phenytoin, carbamazepine, sodium valproate, other anticonvulsants), theophylline, cyclosporin), drug overdose, compliance with drug therapy, cost-effectiveness, pharmacodynamics). It is concluded that therapeutic drug monitoring has a limited, though important, role to play in the overall strategy for drug use in renal disease, and that, for a small number of drugs, such monitoring is essential to help minimize problems of both sub-therapeutic dosing and adverse effects. 33 references.

•

Interstitial Nephritis Source: in Catto, G.R.D. New Clinical Applications-Nephrology: Drugs and the Kidney. Hingham, MA: Kluwer Academic Publishers. p. 37-63. 1990. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $54. ISBN: 0792389182. Summary: This special report discusses the histological features, clinical presentation, putative mechanisms, clinical management, and prognosis of drug-induced tubulointerstitial nephritis (TIN). Following a discussion of histological features, attention is given to clinical features (including acute and chronic drug-induced TIN), a

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comprehensive review of reports of drug-associated TIN (sulfonamides; methicillin; rifampicin; phenindione; diuretics; penicillins; cephalosporins; lithium; phenytoin; allopurinol; cimetidine; and platinum), the pathogenesis of TIN (immune complex deposition; anti-TBM antibody formation; cell-mediated mechanisms), the diagnosis of TIN, and its treatment and prognosis. A critical, authoritative assessment of published studies is made throughout the report. 135 references.

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CHAPTER 6. PERIODICALS AND NEWS ON PHENYTOIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover phenytoin.

News Services and Press Releases One of the simplest ways of tracking press releases on phenytoin is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “phenytoin” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to phenytoin. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “phenytoin” (or synonyms). The following was recently listed in this archive for phenytoin: •

Brand-name, generic phenytoin sodium said to differ; FDA disputes claim Source: Reuters Industry Breifing Date: August 27, 2001

•

Fosphenytoin relieves trigeminal neuralgia crisis Source: Reuters Industry Breifing Date: June 22, 2001

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•

Phenobarbital, phenytoin equally ineffective for neonatal seizures Source: Reuters Medical News Date: August 12, 1999

•

Purple glove syndrome in elderly a complication of multiple dose IV phenytoin Source: Reuters Medical News Date: October 28, 1998

•

Lorazepam more efficacious than phenytoin for overt status epilepticus Source: Reuters Medical News Date: September 17, 1998

•

Warner-Lambert's Fosphenytoin Sodium Injection Cleared For Marketing Source: Reuters Medical News Date: August 19, 1996 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “phenytoin” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “phenytoin” (or synonyms). If you know the name of a company that is relevant to phenytoin, you can go to any stock trading Web site (such as http://www.etrade.com/) and

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search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “phenytoin” (or synonyms).

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

Interpreting Laboratory Values in the Renal Patient Source: Renal Nutrition Forum. 19(1): 1, 3-5. Winter 2000. Summary: This article, from a newsletter for renal (kidney) dietitians, focuses on interpreting laboratory values in the renal patient. The author reminds readers that every measurement in the clinical laboratory is made with an accuracy and precision determined in large part by the test methodology. The author explains the differences between accuracy (how well does the test measure what it is supposed to measure, i.e., validity) and precision (reproducibility, i.e., reliability). Renal failure itself also has a variety of effects on laboratory values. The most common of these result from loss of renal clearance. The renal handling of certain biochemical markers (e.g., serum protein prealbumin) must be considered in clinical interpretation of their values. Another effect from renal failure on laboratory values is the accumulation of normally cleared substances that interfere with an assay; common examples include therapeutic drug monitoring (for phenytoin and vancomycin, for example). Inability to take this reduction in clearance into consideration may lead to under dosing of the drugs involved. A further complication arises when drugs are bound to protein, especially albumin, in plasma (blood). The author concludes that both the clinician and the laboratory need to be aware of the importance of method selection when dealing with patients with renal failure. Two way communication is the key to the proper use of the laboratory results. One appendix reprints a sample monthly lab report, listing the lab test and acceptable level, a blank space for the patient's value to be entered, what to do if the level is too high or too low, the symptoms that the patient may experience, and why the level may have gotten high or low. The lab tests included are: BUN (blood urea nitrogen), albumin, potassium, phosphorus, calcium, and average fluid gain. 1 figure. 3 tables. 9 references.

•

Acid Blockers: How You Can Head Off Heartburn Before It Starts Source: Mayo Clinic Health Letter. 15(11): 7. November 1997.

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Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This brief article from a health newsletter reviews the use of acid blockers or H2 blockers. These drugs have recently become available over the counter (OTC) and can be labelled as acid blockers, acid reducers, or acid controllers. The article explores the use of these medications for treating mild to moderate heartburn, the causes of heartburn, and how OTC acid blockers work. Heartburn results from gastroesophageal reflux, a condition in which stomach acids back up (reflux) into the esophagus. The result is a burning pain behind the breastbone, often accompanied by a sour taste and the sensation of food coming back into the mouth. OTC acid blockers work by blocking the effects of histamine, a chemical that signals the stomach cells to produce acid. Acid blockers differ from traditional antacids in that they can prevent heartburn, not just relieve it. The author reviews possible drug interaction problems (notably Tagamet HB with the asthma drug theophylline, the blood thinner warfarin, or the seizure drug phenytoin). The article stresses that the best way to control heartburn is to determine and avoid what is triggering the attacks. OTC acid blockers and antacids can be helpful for occasional bouts of heartburn, but they aren't meant for severe symptoms or to be taken daily or several times a week. 2 figures. (AA-M). •

TN's Jolting Symptoms and the Drugs That Help Source: TN Alert. p. 1, 6. Spring 1995. Contact: Available from Trigeminal Neuralgia Association. P.O. Box 340, Barnegat Light, NJ 08006. (609) 361-1014. Summary: This newsletter article describes the symptoms of trigeminal neuralgia (TN) and the drugs that may be helpful in its treatment. Topics covered include the typical symptoms of pain associated with TN; factors that may produce TN; diagnostic tests used to confirm the condition; drug therapy, including that with carbamazepine; drug side effects; and other pharmaceutical options, including phenytoin, baclofen, pimozide, capsaicin, and oxcarbazepine.

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

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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for phenytoin. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with phenytoin. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to phenytoin: Anticonvulsants, Hydantoin •

Systemic - U.S. Brands: Cerebyx; Dilantin; Dilantin Infatabs; Dilantin Kapseals; Dilantin-125; Mesantoin; Peganone; Phenytex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202052.html

Lamotrigine •

Systemic - U.S. Brands: Lamictal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202786.html

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

9

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

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•

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

•

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

•

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

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.10 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:11 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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). 11 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 Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “phenytoin” (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 16337 107 992 27 212 17675

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “phenytoin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

12

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

13

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). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16

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 Biologists17 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.18 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.19 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/.

17 Adapted 18

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

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

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Dental Health http://www.nlm.nih.gov/medlineplus/dentalhealth.html Epilepsy http://www.nlm.nih.gov/medlineplus/epilepsy.html Gum Disease http://www.nlm.nih.gov/medlineplus/gumdisease.html Muscle Disorders http://www.nlm.nih.gov/medlineplus/muscledisorders.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on phenytoin. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Dilantin and the Gums Source: Winston-Salem, NC: Comprehensive Epilepsy Program. 1993. [2 p.]. Contact: Available from Comprehensive Epilepsy Program, Bowman Gray School of Medicine, Wake Forest University. 1834 Wake Forest Road, Winston- Salem, NC 27106. (800) 642-0500. PRICE: Single copy free. Summary: This brief brochure reviews the oral side effects of Dilantin (phenytoin), a drug often used to help control seizures, such as those associated with epilepsy. One side effect of Dilantin is swelling or thickening of the gums (gingival hyperplasia), especially around the front teeth. One way to help prevent gum problems is to keep the teeth and mouth very clean, including regular toothbrushing and use of dental floss. The brochure also encourages readers to have a dentist examine the mouth at least once every six months. The brochure offers the toll free telephone number of the Epilepsy Information Service (800-642-0500).

Patient Resources

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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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 “phenytoin” (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 “phenytoin”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “phenytoin” (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 “phenytoin” (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.20

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

20

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)21: •

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/

21

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

Finding Medical Libraries 129

•

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/

Finding Medical Libraries 131

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Phenytoin Dilantin overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002632.htm Phenytoin overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002533.htm

•

Signs & Symptoms for Phenytoin Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm

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Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Muscular stiffness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Nystagmus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003037.htm Sleepiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Swollen gums Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003066.htm Unsteadiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Phenytoin Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Dialysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003421.htm Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm

•

Background Topics for Phenytoin Unconscious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm Vital signs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002341.htm

Online Glossaries 135

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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PHENYTOIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the

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environment. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [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] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and

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stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylate: To treat with an alkylating agent. [EU] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ambulant: Walking or able to walk. [EU]

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Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

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

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of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] 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

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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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antiepileptic: An agent that combats epilepsy. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Anti-Inflammatory Agents, Topical: Anti-inflammatory agents that are applied to the skin and whose pharmacological effect only occurs at the area of application. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] 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 highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antitussive: An agent that relieves or prevents cough. [EU]

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Antitussive Agents: Agents that suppress cough. They act centrally on the medullary cough center. Expectorants, also used in the treatment of cough, act locally. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspartate: A synthetic amino acid. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical

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environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asystole: Cardiac standstill or arrest; absence of a heartbeat; called also Beau's syndrome. [EU]

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] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] 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] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [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] Autonomic: Self-controlling; functionally independent. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [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] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the

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coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Beer: An alcoholic beverage usually made from malted cereal grain (as barley), flavored with hops, and brewed by slow fermentation. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzbromarone: Uricosuric that acts by increasing uric acid clearance. It is used in the treatment of gout. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bethanechol: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, cardiac rate changes, and bronchial spasms. [NIH] Bezoar: A ball of food, mucus, vegetable fiber, hair, or other material that cannot be digested in the stomach. Bezoars can cause blockage, ulcers, and bleeding. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin,

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hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biperiden: A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [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] 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 urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [NIH]

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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Weight Changes: A clinical manifestation consisting of alterations in an individual's weight from his or her norm. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Neoplasms: Tumors or cancer of the breast. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Spasm: Spasmodic contraction of the smooth muscle of the bronchi. [NIH] Bruxism: A disorder characterized by grinding and clenching of the teeth. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central

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nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] 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] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU]

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Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [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] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] 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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH]

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Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cerium: An element of the rare earth family of metals. It has the atomic symbol Ce, atomic number 58, and atomic weight 140.12. Cerium is a malleable metal used in industrial applications. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Chlorpheniramine: A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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]

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Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] 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] Clorazepate Dipotassium: A water-soluble benzodiazepine derivative effective in the treatment of anxiety. It has also muscle relaxant and anticonvulsant actions. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the

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amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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 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] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of

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its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consumption: Pulmonary tuberculosis. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

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] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary 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] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees,

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and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniotomy: An operation in which an opening is made in the skull. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysticercus: The larval form of various tapeworms of the genus Taenia. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae,

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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] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Calculus: Abnormal concretion or calcified deposit that forms around the teeth or dental prostheses. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification.

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[NIH]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermal: Pertaining to or coming from the 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] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH]

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Diarrhea: Passage of excessively liquid or excessively frequent stools. [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] 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] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilantin: A drug that is often used to control seizures. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimenhydrinate: A drug combination that contains diphenhydramine and theophylline. It is used for treating vertigo, motion sickness, and nausea associated with pregnancy. It is not effective in the treatment of nausea associated with cancer chemotherapy. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU]

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Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [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] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH]

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Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] 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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH]

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Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] 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:

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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] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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]

Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethosuximide: An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excisional biopsy: A surgical procedure in which an entire lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH]

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Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in

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diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually

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between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH]

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Gingival Hypertrophy: Abnormal enlargement or overgrowth of the gingivae brought about by enlargement of existing cells. [NIH] Gingival Recession: The exposure of root surface by an apical shift in the position of the gingiva. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] 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] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glutethimide: A hypnotic and sedative. Its use has been largely superseded by other drugs. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid

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metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] 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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

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Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] 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] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoperfusion: Removal of toxins or metabolites from the circulation by the passing of blood, within a suitable extracorporeal circuit, over semipermeable microcapsules containing adsorbents (e.g., activated charcoal) or enzymes, other enzyme preparations (e.g., gel-entrapped microsomes, membrane-free enzymes bound to artificial carriers), or other adsorbents (e.g., various resins, albumin-conjugated agarose). [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels

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carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotropic: Of organisms that cannot live without an external source of organic food. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH]

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Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH]

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Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [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

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

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH]

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Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainate: Glutamate receptor. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [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

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layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] 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] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH]

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Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability,

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requiring periodic, intermittent, or continuous care. [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] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [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]

Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU]

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Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Errors: Errors or mistakes committed by health professionals which result in harm to the patient. They include errors in diagnosis (diagnostic errors), errors in the administration of drugs and other medications (medication errors), errors in the performance of surgical procedures, in the use of other types of therapy, in the use of equipment, and in the interpretation of laboratory findings. Medical errors are differentiated from malpractice in that the former are regarded as honest mistakes or accidents while the latter is the result of negligence, reprehensible ignorance, or criminal intent. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage. [NIH]

MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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 Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

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Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. Before its alphaadrenergic actions became clear, methyldopa was thought to act by inhibiting decarboxylation of DOPA leading to depletion of norepinephrine or by conversion to and release as the false transmitter alpha-methylnorepinephrine. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] 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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH]

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Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [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] Monotherapy: A therapy which uses only one drug. [EU] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] 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,

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nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [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] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Mutilation: Injuries to the body. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH]

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Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrolithiasis: Kidney stones. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [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] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

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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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitrendipine: Ethyl methyl 2,4-dihydro-2,6-dimethyl-4(3-nitrophenyl)-3,5pyridinedicarboxylate. A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. [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] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]

Nizatidine: A histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion. The drug is used for the treatment of duodenal ulcers. [NIH] Nocardia: A genus of gram-positive, aerobic bacteria whose species are widely distributed and are abundant in soil. Some strains are pathogenic opportunists for man and animals. [NIH]

Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal

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transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Nystagmus: Rhythmical oscillation of the eyeballs, either pendular or jerky. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Medicine: Medical specialty concerned with the promotion and maintenance of the physical and mental health of employees in occupational settings. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oestradiol: Growth hormone. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] 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]

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Opacity: Degree of density (area most dense taken for reading). [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] 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] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]

Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU]

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Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH]

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Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatric Dentistry: The practice of dentistry concerned with the dental problems of children, proper maintenance, and treatment. The dental care may include the services provided by dental specialists. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] 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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [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] Periodontist: A specialist in the treatment of diseases of the gums. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [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

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mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenprocoumon: 3-(1-Phenylpropyl)-4-hydroxycoumarin. Long acting oral anticoagulant. It may cause diarrhea. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and

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teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physicochemical: Pertaining to physics and chemistry. [EU] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] 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

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spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polytherapy: A therapy which uses more than one drug. [EU] 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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a

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harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]

Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [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] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH]

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Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Propanolol: Beta blocker. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also).

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The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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 Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU]

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Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [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 Embolism: Embolism in the pulmonary artery or one of its branches. [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]

Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal

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cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [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] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH]

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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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] 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] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is

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incompetent. [EU] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] 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] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [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]

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Rheumatoid: Resembling rheumatism. [EU] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Root Planing: A procedure for smoothing of the roughened root surface or cementum of a tooth after subgingival curettage or scaling, as part of periodontal therapy. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH]

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Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self Mutilation: The act of injuring one's own body to the extent of cutting off or permanently destroying a limb or other essential part of a body. [NIH] Self-Injurious Behavior: Behavior in which persons hurt or harm themselves without the motive of suicide or of sexual deviation. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the

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one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Silver Sulfadiazine: Antibacterial used topically in burn therapy. [NIH] Simethicone: A mixture of dimethyl polysiloxanes and silica gel used as an antiflatulent. Without the addition of silica gel (dimethicone), it is used as an ointment base ingredient and skin protectant. [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 Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH]

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Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] 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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH]

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Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotactic radiosurgery: A radiation therapy technique involving a rigid head frame that is attached to the skull; high-dose radiation is administered through openings in the head frame to the tumor while decreasing the amount of radiation given to normal brain tissue. This procedure does not involve surgery. Also called stereotaxic radiosurgery and stereotactic radiation therapy. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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

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peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Sulfadiazine: A short-acting sulfonamide used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [NIH] Sulfaphenazole: A sulfonilamide anti-infective agent. [NIH] Sun protection factor: SPF. A scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Supratentorial: Located in the upper part of the brain. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects

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similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talc: A native magnesium silicate. [NIH] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tegafur: 5-Fluoro-1-(tetrahydro-2-furanyl)-2,4-(1H,3H)-pyrimidinedione. Congener of fluorouracil with comparable antineoplastic action. It has been suggested especially for the treatment of breast neoplasms. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [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]

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Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [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] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Ticlopidine: Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been

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found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Toothache: Pain in the adjacent areas of the teeth. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH]

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Traction: The act of pulling. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [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 motor to the muscles of mastication. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [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

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specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure

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and flow rate, as well as oxygen content, are increased. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] 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] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] 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] 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] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Voriconazole: A drug that treats infections caused by fungi. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous

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Phenytoin

thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

209

INDEX A Abdomen, 137, 146, 147, 171, 174, 185, 199, 200 Abdominal, 137, 145, 184, 185, 205 Abdominal Pain, 137, 205 Aberrant, 22, 137 Absolute risk, 19, 137 Acatalasia, 137, 149 Acceptor, 137, 174, 183 Acetaminophen, 65, 95, 137, 163 Acidity, 7, 137 Acne, 137, 195 Acoustic, 40, 137 Acremonium, 137, 150 Activities of Daily Living, 18, 137 Acute renal, 8, 16, 137 Adaptation, 33, 64, 137, 187 Adduct, 35, 137 Adenosine, 137, 148, 187, 203 Adjustment, 62, 71, 137 Adrenal Medulla, 138, 149, 161, 181 Adrenaline, 7, 138 Adrenergic, 138, 142, 158, 160, 161, 177, 193, 201, 205 Adrenergic beta-Antagonists, 138, 142 Adsorption, 59, 138 Adsorptive, 138 Adverse Effect, 6, 34, 104, 107, 138, 158, 186, 195, 197 Aerobic, 138, 181 Aerosol, 138, 181 Aetiology, 91, 138 Affinity, 12, 29, 138, 144, 156, 198 Agar, 138, 187 Agarose, 138, 167 Age Groups, 13, 138 Age of Onset, 91, 138 Aged, 80 and Over, 138 Agonist, 138, 144, 145, 158, 160, 177, 202 Albumin, 44, 59, 111, 139, 167, 187 Alertness, 83, 139, 148 Algorithms, 139, 146 Alimentary, 139, 184 Alkaline, 58, 64, 73, 96, 101, 106, 139, 140, 148 Alkaline Phosphatase, 58, 64, 73, 139 Alkaloid, 139, 144, 148, 151, 178, 193, 195, 196, 203

Alkylate, 100, 139 Alkylation, 101, 139 Allogeneic, 139, 166 Allopurinol, 8, 108, 139 Allylamine, 139, 140 Alopecia, 139, 154 Alpha Particles, 139, 193 Alpha-1, 139, 154 Alternative medicine, 110, 139 Aluminum, 139, 201 Alveolar Process, 139, 195 Alveoli, 139, 156 Ambulant, 25, 139 Amenorrhea, 140, 141 Amine, 100, 140, 168 Amino Acid Sequence, 140, 141 Ammonia, 140, 201, 206 Amnestic, 140, 163, 177 Amphetamine, 11, 92, 106, 140, 156 Amygdala, 21, 76, 140, 145, 174, 203 Anabolic, 7, 140, 157 Anabolic Steroids, 7, 140 Anaesthesia, 6, 140, 170 Analgesic, 21, 137, 140, 152, 169, 173, 178, 181, 183, 193 Analog, 140, 156, 163, 177 Analytes, 90, 99, 100, 140 Anatomical, 140, 144, 150, 160, 170, 174, 177, 196 Anemia, 35, 140, 163, 175 Anesthesia, 5, 6, 30, 48, 56, 90, 140, 141, 173, 177, 180, 189 Anesthetics, 141, 145, 161 Angina, 138, 141, 172 Angina Pectoris, 138, 141, 172 Anginal, 141, 181 Angiotensin-Converting Enzyme Inhibitors, 141, 142 Animal model, 11, 21, 26, 91, 141 Anions, 139, 141, 172, 197, 201 Anisotropy, 141, 163 Anomalies, 35, 141, 202 Anorexia, 107, 141 Anorexia Nervosa, 107, 141 Antagonism, 141, 148, 157, 203 Antibacterial, 4, 141, 198, 199, 206 Antibiotic, 95, 141, 147, 189, 196, 199, 205

210

Phenytoin

Antibodies, 15, 89, 99, 100, 141, 166, 168, 175, 187, 193 Antibody, 67, 90, 108, 138, 141, 142, 163, 166, 168, 169, 170, 172, 176, 178, 193, 199, 208 Anticholinergic, 92, 142 Anticoagulant, 142, 186, 191, 207 Anticonvulsant, 4, 12, 21, 25, 39, 40, 43, 51, 54, 58, 76, 91, 92, 93, 94, 107, 142, 148, 151, 161, 177, 186, 206 Antidepressant, 89, 142, 163 Antiemetic, 142, 157, 158, 177 Antiepileptic, 12, 13, 22, 24, 25, 26, 60, 91, 93, 94, 101, 142 Antigen, 48, 99, 138, 141, 142, 163, 168, 169, 170, 176, 177 Antihypertensive, 23, 142, 177, 181, 195 Antihypertensive Agents, 23, 142 Anti-infective, 142, 150, 169, 201 Anti-inflammatory, 4, 18, 137, 142, 143, 154, 156, 165, 169, 196 Anti-Inflammatory Agents, 18, 142, 143, 154 Anti-Inflammatory Agents, Topical, 18, 142 Antimetabolite, 142, 163, 177 Antimicrobial, 142, 151 Antineoplastic, 142, 154, 163, 177, 202, 204 Antioxidant, 41, 142, 183 Antiproliferative, 28, 142 Antipyretic, 137, 142, 193 Antispasmodic, 142, 183, 196 Antithrombotic, 142, 204 Antitussive, 91, 142, 143, 156, 157, 183 Antitussive Agents, 91, 143 Antiviral, 143, 171, 180 Anus, 143, 147, 152, 194 Anxiety, 21, 138, 143, 151, 163, 182, 184, 189 Anxiolytic, 143, 177 Apoptosis, 15, 143 Aqueous, 76, 89, 90, 93, 94, 96, 97, 143, 145, 155, 169, 174 Arachidonic Acid, 143, 190 Arginine, 96, 143 Aromatic, 12, 92, 143 Arrhythmia, 143, 207 Arterial, 49, 139, 143, 169, 173, 191 Arteries, 143, 146, 147, 153, 177, 179 Arteriosclerosis, 143, 204 Arteriovenous, 143, 204 Arteriovenous Fistula, 143, 204

Artery, 143, 146, 153, 159, 192, 207 Aspartate, 18, 143, 156, 173, 186 Asphyxia, 92, 93, 143, 181 Aspirin, 7, 83, 143 Assay, 15, 39, 89, 95, 100, 107, 111, 143, 169, 196 Astrocytes, 143, 177, 178 Asystole, 46, 69, 144 Ataxia, 89, 144, 203 Atrial, 144, 208 Atrial Fibrillation, 144, 208 Atrioventricular, 46, 144 Atrium, 144, 207 Atrophy, 13, 37, 42, 144, 180 Atropine, 144, 196 Atypical, 15, 18, 144, 182 Auditory, 144, 161 Autonomic, 94, 144, 164, 181, 185, 199, 201 Axons, 144, 156, 193, 199 B Babesiosis, 144, 193 Baclofen, 5, 6, 112, 144 Bacteria, 67, 88, 138, 141, 142, 144, 145, 152, 155, 159, 161, 164, 166, 177, 181, 199, 204, 205, 206 Bacterial Infections, 105, 144 Bacterial Physiology, 137, 144 Bactericidal, 144, 161 Bacteriophage, 144, 187, 205 Bacteriuria, 145, 206 Barbiturate, 77, 78, 145 Basal Ganglia, 144, 145, 174 Basal Ganglia Diseases, 144, 145 Base, 16, 23, 28, 33, 100, 145, 155, 172, 193, 198, 202 Basement Membrane, 145, 162 Beer, 9, 145 Benign, 9, 17, 145, 167, 180, 193 Benzbromarone, 15, 145 Beta-Thromboglobulin, 145, 171 Bethanechol, 9, 145 Bezoar, 72, 145 Bile, 145, 163, 164, 174, 200, 201 Bile Acids, 145, 164, 200 Bilirubin, 139, 145 Bioassays, 15, 145 Bioavailability, 36, 74, 96, 107, 146 Biochemical, 27, 53, 54, 66, 73, 111, 142, 146, 186, 197 Biological Markers, 100, 146 Biological response modifier, 146, 171 Biopsy, 8, 146, 161, 185

Index 211

Biotechnology, 30, 104, 110, 119, 146 Biotin, 14, 81, 146 Biperiden, 73, 146 Bipolar Disorder, 22, 146 Bladder, 146, 152, 154, 170, 191, 195, 206 Bloating, 146, 170 Blood Coagulation, 146, 148, 196, 203 Blood Glucose, 7, 146, 167 Blood Platelets, 146, 197 Blood pressure, 134, 142, 146, 164, 169, 178, 181, 198 Blood urea, 111, 146 Blood vessel, 146, 147, 148, 149, 150, 159, 160, 165, 172, 192, 198, 199, 200, 203, 207 Body Fluids, 147, 158, 182, 198 Body Weight Changes, 72, 147 Bone Marrow, 147, 154, 166, 175, 178 Bone Resorption, 4, 147 Bowel, 7, 147, 157, 171, 185, 205 Bowel Movement, 7, 147, 157 Brachytherapy, 147, 171, 172, 193, 208 Brain Stem, 147, 150 Branch, 131, 147, 159, 184, 199, 203 Breakdown, 146, 147, 157, 164 Breast Neoplasms, 147, 202 Broad-spectrum, 147, 150 Bronchi, 147, 161, 203, 204 Bronchial, 145, 147, 168, 203 Bronchial Spasm, 145, 147 Bruxism, 103, 147 Buccal, 147, 175 Bulimia, 107, 147 Bupivacaine, 147, 174 Burns, 106, 147 Burns, Electric, 147 Bypass, 147, 204 C Caffeine, 7, 11, 147 Calcium, 3, 6, 111, 142, 148, 157, 172, 181, 183, 198, 207 Calcium channel blocker, 3, 142, 148, 181, 207 Calcium Channel Blockers, 3, 142, 148, 181 Camptothecin, 148, 172 Candidiasis, 105, 148 Candidosis, 148 Cannabidiol, 148 Cannabinoids, 95, 148 Cannabinol, 148 Capsaicin, 18, 112, 148 Capsules, 36, 44, 74, 84, 98, 148, 164, 165 Carbohydrate, 107, 148, 153, 165, 166, 188

Carcinogen, 100, 137, 149 Carcinogenesis, 51, 54, 105, 149, 150 Carcinogenic, 149, 171, 190, 200 Cardiorespiratory, 149, 177 Cardiotonic, 149, 157 Cardiovascular, 140, 149, 197 Case report, 6, 8, 9, 43, 46, 54, 55, 58, 63, 64, 72, 149, 151 Catalase, 54, 137, 149 Catecholamine, 149, 158, 186 Catheter, 84, 149 Cauda Equina, 149, 196 Causal, 91, 149, 160 Celiac Disease, 107, 149 Cell, 21, 70, 77, 99, 108, 137, 139, 143, 144, 146, 148, 149, 150, 151, 153, 154, 155, 156, 160, 161, 162, 163, 164, 166, 168, 171, 173, 176, 177, 178, 181, 182, 187, 188, 190, 194, 195, 198, 199, 201, 202, 203, 204, 205, 206, 208 Cell Death, 143, 149 Cell Differentiation, 149, 198 Cell Division, 144, 149, 176, 178, 187, 190 Cell membrane, 148, 149, 156, 164, 188, 199 Cell proliferation, 99, 143, 149, 198 Cellobiose, 149 Cellulose, 68, 149, 163, 187 Centrifugation, 150, 177 Cephalosporins, 8, 108, 150 Cerebellar, 37, 42, 144, 150, 194 Cerebellum, 77, 150, 194 Cerebral, 104, 144, 145, 147, 150, 153, 161, 162, 175, 192, 202 Cerebral Cortex, 144, 150, 162, 192 Cerebral Palsy, 104, 150 Cerebrospinal, 37, 59, 150 Cerebrospinal fluid, 37, 59, 150 Cerebrovascular, 145, 148, 150, 203 Cerebrum, 150, 205 Cerium, 88, 150 Chemopreventive, 10, 150 Chemotherapy, 61, 106, 150, 157 Chin, 39, 57, 150, 176 Chlorhexidine, 105, 150 Chloroquine, 9, 150 Chlorpheniramine, 97, 98, 150 Cholesterol, 8, 145, 150, 200, 202 Chromatin, 143, 150, 160, 181 Chromosome, 151, 153, 174 Chronic renal, 107, 151 Cimetidine, 7, 9, 44, 108, 151

212

Phenytoin

Cinchona, 151, 193 Ciprofloxacin, 38, 52, 56, 66, 151 Clamp, 21, 30, 151 Clinical Medicine, 54, 151, 189 Clinical study, 151, 153 Clinical trial, 10, 23, 29, 39, 83, 84, 119, 151, 153, 154, 158, 191, 194 Clonazepam, 6, 151 Clonic, 13, 78, 93, 151, 177 Cloning, 146, 151 Clorazepate Dipotassium, 4, 151 Coagulation, 146, 151, 168, 187, 207 Coca, 151 Cocaine, 45, 84, 95, 151 Codeine, 152, 156, 183 Coenzyme, 152, 163 Cofactor, 152, 191, 203 Colitis, 152 Collagen, 15, 98, 99, 140, 145, 152, 162, 164, 187, 190 Colloidal, 139, 152, 159, 197 Colon, 152, 171, 173, 205 Combination Therapy, 72, 152 Compliance, 107, 152 Compress, 5, 152 Computational Biology, 119, 152 Concomitant, 6, 32, 39, 42, 46, 60, 63, 66, 70, 152 Concretion, 152, 155 Conduction, 152, 180, 203 Cone, 152, 201 Congenita, 152, 193 Conjugated, 29, 152, 154, 166, 167, 179 Conjugation, 152, 165 Conjunctiva, 152, 153, 205 Connective Tissue, 6, 9, 15, 60, 99, 147, 152, 153, 156, 162, 164, 195, 202 Connective Tissue Cells, 153 Consciousness, 140, 153, 157, 161, 192, 195, 199 Consumption, 9, 17, 153, 156, 195 Contraindications, ii, 106, 153 Controlled clinical trial, 69, 153 Controlled study, 33, 153 Convulsions, 72, 133, 142, 145, 153, 159 Convulsive, 30, 89, 94, 96, 153, 159 Coordination, 17, 59, 150, 153 Coronary, 141, 153, 177, 179, 204 Coronary Thrombosis, 153, 177, 179 Cortex, 11, 153, 154, 160, 161, 190, 194 Cortical, 11, 91, 153, 161, 193, 197, 203 Corticosteroid, 153, 189

Cortisol, 139, 154 Cortisone, 154, 156 Coumarin, 7, 11, 12, 16, 154 Cranial, 68, 150, 154, 167, 180, 184, 185, 205 Craniotomy, 39, 69, 154 Curative, 154, 181, 203 Curettage, 154, 196 Cutaneous, 8, 40, 62, 66, 69, 148, 154, 175, 184, 187 Cyclic, 148, 154, 188, 190, 203 Cyclodextrins, 76, 77, 154 Cyclophosphamide, 46, 154 Cyclosporine, 3, 8, 9, 42, 99, 154 Cysticercus, 40, 154 Cystitis, 8, 154 Cytochrome, 5, 10, 17, 18, 24, 27, 28, 35, 51, 56, 57, 70, 76, 77, 151, 154 Cytokine, 154, 171 Cytomegalovirus, 34, 154 Cytoplasm, 143, 149, 155, 160, 166, 178, 181 Cytotoxic, 148, 155, 193, 198 D Data Collection, 17, 155 De novo, 28, 155 Deamination, 155, 178, 206 Decarboxylation, 155, 168, 177, 206 Decompression, 5, 155 Decubitus, 71, 155 Decubitus Ulcer, 71, 155 Degenerative, 155, 168 Dehydration, 7, 155 Deletion, 143, 155 Delivery of Health Care, 155, 167 Delusions, 155, 192 Dendrites, 21, 155, 156, 181, 193 Density, 58, 150, 155, 183, 188, 199 Dental Calculus, 105, 155 Dental Care, 106, 107, 155, 185 Dental Caries, 107, 155, 156 Dental Plaque, 6, 156 Dentate Gyrus, 77, 156, 168 Dentition, 105, 156 Depolarization, 30, 156, 198 Depressive Disorder, 156, 174 Dermal, 31, 66, 99, 156 Dermatosis, 63, 156 Dermis, 9, 99, 156, 201, 205 Developing Countries, 63, 156 Dexamethasone, 42, 48, 156 Dextroamphetamine, 140, 156

Index 213

Dextromethorphan, 91, 156 Diagnostic Errors, 156, 176 Diagnostic procedure, 87, 110, 156, 186 Dialysate, 156 Dialyzer, 68, 156, 167 Diarrhea, 7, 157, 186 Digestion, 139, 145, 147, 157, 158, 170, 171, 174, 185, 200 Digestive system, 85, 157, 179 Digitalis, 76, 157 Digoxigenin, 95, 157 Dihydrotestosterone, 157, 194 Dihydroxy, 49, 54, 157 Dilantin, 4, 5, 13, 43, 44, 59, 93, 103, 104, 105, 114, 124, 133, 157 Diltiazem, 98, 99, 157 Dilution, 94, 157 Dimenhydrinate, 92, 157 Dimethyl, 157, 172, 181, 198 Diphenhydramine, 157 Direct, iii, 18, 22, 25, 29, 37, 58, 84, 88, 95, 113, 151, 157, 158, 193, 194, 202 Discrete, 12, 157, 174 Disinfectant, 150, 157, 161 Disposition, 27, 32, 44, 49, 55, 56, 77, 107, 157 Dissociation, 138, 157 Distal, 6, 27, 157, 159, 164, 185, 191 Diuresis, 106, 148, 157, 203 Diuretics, Thiazide, 142, 158 Dizziness, 92, 158, 184, 207 Domperidone, 9, 158 Dopamine, 140, 152, 156, 158, 177, 178, 181 Dorsal, 21, 158, 188, 199 Double-blind, 18, 31, 56, 57, 158 Double-blinded, 56, 158 Drug Delivery Systems, 97, 158 Drug Interactions, 5, 12, 13, 15, 17, 18, 24, 27, 47, 57, 114, 158 Drug Monitoring, 32, 33, 39, 40, 44, 47, 48, 51, 53, 56, 60, 63, 67, 73, 100, 107, 111, 158 Drug Tolerance, 158, 204 Drug Toxicity, 24, 158 Duct, 158, 196, 201 Duodenal Ulcer, 158, 181 Duodenum, 145, 158, 160, 184, 200 Dyskinesia, 43, 73, 158 Dyspepsia, 158, 170 E Eclampsia, 43, 46, 58, 145, 159 Effector, 18, 159

Efficacy, 4, 10, 12, 18, 24, 29, 30, 38, 39, 43, 46, 61, 106, 159 Elastic, 99, 159, 165, 199 Elasticity, 99, 143, 159, 198 Elastin, 152, 159 Elective, 159 Electrode, 40, 159 Electrolyte, 153, 159, 182, 188, 198 Electrophoresis, 159, 189 Electrophysiological, 26, 159 Electroshock, 25, 159 Emboli, 8, 159, 208 Embolism, 159, 192, 208 Embolization, 159, 208 Embryo, 149, 159, 170 Emergency Medicine, 55, 72, 159 Emergency Treatment, 159 Emollient, 159, 166 Empiric, 6, 159 Empirical, 94, 159 Enamel, 155, 160 Endemic, 160, 175, 199 Endocarditis, 148, 160 Endocrine Glands, 160 Endogenous, 99, 158, 160, 165, 191 Endoscopic, 160, 177 Endothelial cell, 160, 171, 203 End-stage renal, 151, 160 Enhancer, 27, 160 Entorhinal Cortex, 160, 168 Environmental Exposure, 146, 160, 182 Environmental Health, 118, 120, 160 Enzymatic, 140, 148, 155, 160, 168 Eosinophils, 8, 160, 166, 173 Ephedrine, 46, 92, 160 Epidemiologic Studies, 146, 160 Epidemiological, 26, 160 Epidermal, 63, 72, 160, 172 Epidermis, 156, 160, 172 Epilepticus, 30, 161 Epinephrine, 7, 138, 158, 161, 181 Epithelial, 161, 168, 172 Epithelial Cells, 161, 168, 172 Erythrocytes, 140, 144, 147, 161, 194 Esophagitis, 161, 201 Esophagus, 112, 157, 161, 164, 167, 175, 186, 194, 200 Estrogen, 161, 190, 197, 202 Ethanol, 96, 161, 162 Ether, 90, 100, 161 Ethosuximide, 4, 91, 100, 161 Evoked Potentials, 77, 161

214

Phenytoin

Excipient, 98, 161 Excisional, 8, 161 Excisional biopsy, 8, 161 Excitability, 21, 91, 161, 179, 193 Excitatory, 30, 144, 161, 165 Exfoliation, 161, 179 Exhaustion, 141, 161, 175 Exogenous, 106, 138, 160, 162, 165, 191 External-beam radiation, 162, 172, 193, 208 Extracellular, 6, 59, 76, 99, 143, 153, 162, 183, 198 Extracellular Matrix, 6, 99, 153, 162, 183 Extracellular Space, 162 Extracorporeal, 162, 167 Extraction, 6, 42, 52, 59, 89, 162 Extrapyramidal, 146, 158, 162 Extravasation, 48, 53, 162, 167 Extremity, 48, 162, 173 F Facial, 74, 162 Family Planning, 119, 162 Famotidine, 10, 162 Fat, 143, 147, 153, 155, 159, 162, 173, 174, 195, 199 Fatty acids, 139, 162, 165, 190 Femur, 162, 203 Fenfluramine, 7, 106, 162 Fermentation, 145, 162 Fetus, 162, 189 Fibroblasts, 15, 45, 59, 66, 70, 99, 153, 162, 171 Fibrosis, 9, 15, 107, 139, 162, 196 Fibula, 162, 203 Fissure, 107, 156, 162 Flatus, 162, 164 Fluorescence, 47, 89, 162, 163 Fluorescence Polarization, 47, 163 Fluorouracil, 78, 163, 202 Fluoxetine, 43, 163 Fluvoxamine, 78, 163 Folate, 14, 77, 78, 80, 81, 163 Fold, 29, 162, 163 Folic Acid, 35, 70, 78, 80, 81, 163 Fossa, 150, 163 Free Radicals, 142, 157, 163 Fulminant Hepatic Failure, 33, 163 Fungi, 152, 163, 166, 177, 203, 207, 208 Fungus, 148, 150, 163 G GABA, 25, 144, 151, 163, 198, 206 Gallbladder, 137, 157, 163

Gamma Rays, 163, 193 Ganglia, 145, 164, 180, 185, 199, 201 Ganglionic Blockers, 142, 164 Gap Junctions, 164, 202 Gas, 7, 41, 89, 140, 162, 164, 169, 170, 181, 195, 207 Gas exchange, 164, 195 Gastric, 7, 9, 97, 134, 151, 162, 164, 167, 168, 177, 181, 182, 185, 194 Gastric Juices, 97, 164, 185 Gastrin, 151, 164, 168 Gastritis, 164, 201 Gastroesophageal Reflux, 9, 112, 164 Gastrointestinal, 9, 151, 158, 161, 164, 175, 194, 197, 201 Gastrointestinal tract, 161, 164, 197 Gastrostomy, 67, 164 Gelatin, 164, 166, 201 Gene, 11, 27, 45, 104, 146, 164, 172, 182, 187 Gene Expression, 11, 27, 164 Genital, 35, 151, 164 Genotype, 17, 25, 164, 186 Gestation, 164, 185 Gingival Hyperplasia, 3, 8, 48, 54, 58, 71, 107, 124, 164 Gingival Hypertrophy, 6, 165 Gingival Recession, 105, 165 Gingivitis, 105, 107, 156, 165 Ginkgo biloba, 17, 83, 165 Ginseng, 17, 165 Gland, 138, 153, 154, 165, 184, 191, 196, 197, 200, 201, 203 Glomerular, 8, 165, 181, 195 Glomerular Filtration Rate, 165, 181 Glomeruli, 165, 192 Glomerulonephritis, 8, 165 Glomerulus, 165, 180 Glucans, 154, 165 Glucocorticoid, 32, 156, 165, 189 Glucose, 7, 146, 149, 154, 165, 167, 196 Glucuronosyltransferase, 13, 165 Glutamate, 18, 20, 156, 165, 172 Glutamic Acid, 163, 165, 181, 190 Gluten, 149, 165 Glutethimide, 100, 165 Glycerol, 5, 165 Glycine, 140, 166, 181 Glycoproteins, 166, 172, 176, 188, 199 Gonad, 166 Gonadal, 77, 166, 200 Gout, 145, 166

Index 215

Governing Board, 166, 189 Graft, 5, 166, 192 Graft Rejection, 5, 166 Graft-versus-host disease, 166, 192 Gram-positive, 166, 181 Granule, 77, 156, 166 Granulocytes, 166, 198, 208 Granuloma, 8, 40, 166 Grasses, 163, 166 Growth, 6, 15, 140, 141, 142, 143, 146, 149, 156, 166, 171, 172, 175, 177, 180, 182, 187, 203, 204, 205, 208 H Hair follicles, 156, 166 Half-Life, 72, 166 Hallucinogen, 166, 186 Haptens, 138, 166 Hay Fever, 150, 166 Headache, 148, 167 Health Care Costs, 15, 167 Health Expenditures, 167 Health Services, 16, 155, 167 Heart failure, 141, 160, 167 Heartbeat, 144, 167 Heartburn, 7, 111, 112, 167, 170 Hematoma, 96, 167 Hematuria, 8, 167 Heme, 9, 145, 154, 167, 179, 188, 206 Hemodialysis, 106, 156, 167 Hemoglobin, 140, 161, 167, 188 Hemoglobin A, 167, 188 Hemoperfusion, 37, 106, 167 Hemorrhage, 29, 63, 96, 167, 200 Hemorrhoids, 7, 167 Hemostasis, 167, 197 Hepatic, 14, 61, 139, 168, 178, 188 Hepatitis, 9, 163, 168 Hepatocytes, 18, 27, 168 Herbicide, 106, 168 Hereditary, 15, 166, 168, 180 Heredity, 164, 168 Herpes, 105, 168 Herpes Zoster, 168 Heterogeneity, 138, 168 Heterotropic, 18, 168 Hippocampus, 26, 30, 76, 156, 168, 174, 192, 200 Histamine, 112, 150, 151, 157, 162, 168, 181, 190, 194 Histidine, 16, 168 Homogeneous, 100, 168 Homologous, 154, 168, 202

Hormonal, 144, 154, 168 Hormone, 138, 146, 153, 154, 161, 164, 168, 182, 190, 198, 203 Humoral, 166, 168 Hybrid, 12, 168 Hybridomas, 168, 171 Hydrogen, 137, 140, 145, 148, 149, 169, 174, 178, 181, 183, 191, 201 Hydrogen Peroxide, 149, 169, 174, 201 Hydrolysis, 149, 157, 169, 186, 191 Hydrophilic, 76, 169 Hydroxylation, 53, 56, 65, 76, 169 Hydroxylysine, 152, 169 Hydroxyproline, 140, 152, 169 Hyperplasia, 3, 54, 106, 169 Hypersensitivity, 31, 32, 36, 42, 49, 69, 77, 157, 169 Hypertension, 138, 141, 142, 148, 167, 169, 172, 189 Hypertrophy, 52, 169 Hypnotic, 145, 157, 165, 169, 177 Hypotension, 145, 153, 164, 169 Hypothermia, 44, 53, 54, 169 I Ibuprofen, 83, 169 Id, 79, 125, 130, 132, 169 Idiopathic, 65, 146, 169 Ileum, 34, 169 Imidazole, 146, 168, 169, 194 Immune response, 142, 154, 166, 169, 170, 201, 207 Immune system, 169, 170, 175, 206, 208 Immunoassay, 33, 48, 79, 89, 90, 95, 99, 100, 169 Immunodeficiency, 32, 44, 170, 201 Immunodeficiency syndrome, 170, 201 Immunoglobulin, 141, 170, 178 Immunologic, 9, 169, 170, 193 Immunology, 138, 170 Immunosuppressant, 5, 8, 163, 170, 177 Immunosuppressive, 154, 165, 170, 202 Impairment, 11, 19, 69, 144, 158, 170, 176, 192 Implant radiation, 170, 171, 172, 193, 208 In vitro, 5, 11, 13, 14, 15, 17, 18, 26, 56, 59, 63, 64, 65, 70, 77, 170, 196, 202 In vivo, 5, 10, 18, 36, 54, 55, 57, 59, 63, 78, 79, 91, 97, 98, 170, 202 Incision, 170, 172 Incompetence, 164, 170 Incontinence, 160, 170, 196 Indicative, 91, 104, 170, 184, 207

216

Phenytoin

Indigestion, 7, 170 Induction, 17, 27, 46, 71, 77, 99, 159, 164, 170, 173, 190 Infancy, 78, 170 Infant, Newborn, 138, 170 Infarction, 170, 204 Infiltration, 165, 170, 189 Inflammatory bowel disease, 9, 171 Infusion, 36, 46, 56, 67, 68, 69, 171 Ingestion, 17, 171, 188 Inhalation, 138, 171, 172, 188 Initiation, 30, 32, 58, 66, 171, 174 Inner ear, 171, 206 Insight, 11, 22, 27, 171 Interferon, 9, 171 Interferon-alpha, 171 Interleukin-6, 45, 171 Interleukin-8, 45, 171 Intermittent, 171, 175, 185, 188 Internal radiation, 171, 172, 193, 208 Interstitial, 8, 107, 147, 162, 171, 172, 180, 195, 208 Intervertebral, 171, 196 Intervertebral Disk Displacement, 171, 196 Intestinal, 78, 149, 171, 172, 175 Intestinal Mucosa, 149, 171 Intestine, 7, 97, 147, 171, 173, 185 Intoxication, 37, 51, 67, 68, 78, 171, 208 Intracellular, 148, 170, 171, 188, 190, 194, 198 Intramuscular, 50, 96, 172, 184 Intramuscular injection, 96, 172 Intravenous, 14, 34, 36, 39, 48, 50, 53, 55, 56, 60, 94, 96, 171, 172, 184 Intrinsic, 11, 91, 138, 145, 172 Invasive, 5, 172 Involuntary, 89, 145, 172, 179, 199 Ion Channels, 91, 144, 172, 186, 202 Ionizing, 139, 160, 172, 193 Ions, 137, 145, 157, 158, 159, 169, 172, 178, 188, 199 Irinotecan, 34, 55, 172 Irradiation, 9, 172, 208 Ischemia, 141, 144, 155, 172 Isoflurane, 6, 172 Isopropyl, 100, 172 Isradipine, 38, 172 J Joint, 5, 9, 151, 172, 202 K Kainate, 26, 157, 172

Kb, 118, 172 Keratinocyte growth factor, 73, 172 Keratinocytes, 171, 172 Keratolytic, 155, 173 Ketamine, 173, 186 Ketoacidosis, 173 Ketone Bodies, 173 Ketosis, 4, 173 Kidney Disease, 8, 37, 85, 118, 173 Kidney stone, 8, 173, 180, 206 Kinetic, 13, 18, 172, 173 L Large Intestine, 157, 171, 173, 194, 198 Lavage, 134, 173 Least-Squares Analysis, 173, 194 Leg Ulcer, 31, 71, 173 Lethal, 28, 144, 173 Lethargy, 92, 173 Leukocytes, 147, 160, 166, 171, 173, 178, 181 Levorphanol, 156, 173 Library Services, 130, 173 Lice, 20, 173 Lidocaine, 10, 65, 92, 174, 177 Ligands, 12, 16, 174 Likelihood Functions, 174, 194 Limbic, 21, 140, 174 Limbic System, 140, 174 Linear Models, 174, 194 Linkage, 66, 90, 149, 174 Lipid, 41, 67, 143, 165, 174, 177, 183 Lipid Peroxidation, 67, 174, 183 Liquor, 174, 192 Lithium, 7, 106, 107, 108, 174 Loading dose, 50, 174 Lobe, 26, 93, 174, 184 Localization, 25, 174 Localized, 8, 155, 167, 170, 174, 178, 187, 196, 205, 206 Logistic Models, 174, 194 Long-Term Care, 53, 174 Loop, 16, 175 Lower Esophageal Sphincter, 164, 175 Lupus, 69, 175, 202 Lymphatic, 170, 175, 199 Lymphocyte, 142, 175, 176 Lymphoid, 141, 175 M Malabsorption, 149, 175 Malaria, 28, 61, 151, 175 Malaria, Falciparum, 175 Malaria, Vivax, 175

Index 217

Malignant, 71, 142, 175, 176, 180, 193 Malnutrition, 139, 144, 175 Mammary, 175, 202 Mandible, 139, 150, 175, 195 Mania, 56, 175 Manic, 146, 174, 175, 192 Manic-depressive psychosis, 175, 192 Mastication, 3, 15, 103, 175, 205 Maxillary, 8, 175, 184 Medial, 143, 176, 203 Mediate, 158, 176, 194 Mediator, 27, 176, 197 Medical Errors, 16, 176 Medical Staff, 158, 176 Medicament, 97, 176, 201 Medication Errors, 16, 19, 176 MEDLINE, 119, 176 Medullary, 143, 156, 176 Medulloblastoma, 77, 176 Megaloblastic, 163, 176 Meiosis, 176, 202 Membrane Glycoproteins, 176 Memory, 83, 141, 176 Meninges, 149, 176 Mental, iv, 10, 16, 83, 85, 89, 103, 118, 120, 150, 157, 170, 175, 176, 182, 192, 196, 206 Mental Disorders, 85, 176, 192 Mental Health, iv, 10, 85, 118, 120, 176, 182 Mental Processes, 157, 176, 192 Mental Retardation, 104, 176 Mephenytoin, 11, 17, 58, 177 Mercaptopurine, 10, 177 Metabolite, 12, 13, 39, 49, 51, 54, 58, 63, 157, 177, 182, 189 Methotrexate, 10, 177 Methyldopa, 8, 177 Metoclopramide, 10, 177 Mexiletine, 6, 177 MI, 51, 77, 88, 92, 135, 177 Microbe, 177, 204 Microbiology, 137, 144, 145, 177 Microglia, 144, 177, 178 Microorganism, 152, 177, 184, 207 Micro-organism, 155, 177 Microsomal, 13, 76, 77, 177 Midazolam, 11, 177 Misoprostol, 10, 177 Mitosis, 143, 178 Mobility, 16, 178 Modeling, 12, 14, 23, 178 Modification, 140, 178, 193

Molecular, 15, 27, 28, 72, 73, 91, 99, 100, 119, 121, 146, 152, 156, 163, 178, 189, 190, 194, 201, 204, 205 Molecular Structure, 178, 205 Molecule, 19, 99, 142, 145, 152, 157, 159, 169, 178, 183, 193, 194, 198, 201 Monitor, 16, 89, 178, 182 Monoamine, 8, 140, 156, 178, 205 Monoamine Oxidase, 8, 140, 156, 178, 205 Monoclonal, 15, 168, 172, 178, 193, 208 Monocytes, 171, 173, 178 Mononuclear, 166, 178 Monotherapy, 22, 25, 36, 40, 45, 54, 55, 57, 60, 67, 70, 72, 78, 178 Morphine, 152, 178, 179, 183 Morphology, 77, 178 Motility, 178, 197 Motion Sickness, 62, 91, 92, 157, 178, 179, 190, 196 Motor Activity, 153, 178 Mucins, 156, 166, 178, 196 Mucociliary, 178, 198 Mucosa, 175, 179, 190, 201 Mucositis, 106, 179, 203 Mucus, 145, 178, 179, 205 Muscle relaxant, 151, 179, 186 Muscle Relaxation, 179, 180 Muscle Spindles, 179, 186 Mutilation, 107, 179 Mydriatic, 179, 196 Myocardial infarction, 145, 153, 177, 179, 208 Myocardium, 141, 177, 179 Myoglobin, 179, 188 Myotonia, 179, 193 N Narcolepsy, 156, 160, 179 Narcosis, 179 Narcotic, 6, 173, 178, 179, 181 Nausea, 7, 142, 157, 170, 173, 179, 184, 206 NCI, 1, 85, 117, 179 Necrolysis, 63, 72, 179 Need, 3, 4, 22, 28, 93, 94, 100, 103, 105, 106, 111, 126, 138, 151, 179, 204 Nelfinavir, 32, 180 Neonatal, 61, 77, 110, 180 Neoplasms, 142, 180, 193, 203 Nephritis, 8, 107, 180 Nephrolithiasis, 8, 180 Nephropathy, 173, 180 Nephrosis, 180 Nephrotic, 8, 180

218

Phenytoin

Nephrotoxic, 16, 180 Nerve, 5, 18, 138, 140, 144, 149, 150, 155, 176, 178, 180, 185, 188, 189, 196, 199, 200, 205 Nerve Growth Factor, 18, 180 Nervous System, 11, 51, 91, 94, 140, 148, 149, 151, 156, 160, 161, 163, 164, 165, 167, 176, 177, 178, 180, 181, 185, 196, 197, 201, 202, 203, 205 Neural, 11, 21, 26, 164, 168, 177, 178, 180, 199 Neuralgia, 4, 5, 50, 109, 112, 180 Neurodegenerative Diseases, 29, 92, 93, 145, 180 Neurologic, 28, 38, 180 Neurologist, 29, 180 Neuromuscular, 35, 66, 124, 180, 203 Neuromuscular Blockade, 66, 180 Neuromuscular Junction, 180 Neuronal, 21, 26, 91, 179, 180 Neurons, 21, 30, 91, 152, 155, 156, 161, 164, 179, 180, 181, 192, 199, 201, 202 Neuropathy, 6, 18, 181, 185, 196 Neurophysiology, 69, 156, 181 Neurotoxicity, 156, 181 Neurotransmitter, 137, 140, 158, 163, 165, 166, 168, 172, 181, 198, 200, 202, 205 Neutrons, 139, 172, 181, 193 Neutrophils, 166, 171, 173, 181 Niacin, 7, 181, 205 Nifedipine, 8, 15, 43, 48, 54, 98, 99, 107, 181 Nitrendipine, 76, 181 Nitrogen, 16, 101, 111, 138, 139, 140, 154, 181, 205 Nitrous Oxide, 6, 181 Nizatidine, 10, 32, 181 Nocardia, 48, 181, 196 Norepinephrine, 138, 158, 160, 177, 181, 195 Nortriptyline, 89, 182 Nuclear, 27, 145, 148, 152, 164, 174, 182 Nuclei, 139, 140, 153, 174, 178, 181, 182, 191 Nucleic acid, 181, 182 Nucleus, 143, 145, 150, 154, 155, 160, 163, 171, 176, 178, 181, 182, 190, 191, 203 Nursing Care, 106, 182 Nutritional Support, 164, 182 Nystagmus, 89, 134, 182 O Obsessive-Compulsive Disorder, 163, 182

Occult, 95, 182 Occupational Medicine, 16, 182 Odds Ratio, 182, 195 Odour, 143, 182 Oestradiol, 59, 182 Oliguria, 8, 182 Omeprazole, 5, 10, 32, 65, 182 Oncogene, 54, 182 Opacity, 8, 155, 183 Opiate, 95, 178, 183 Opium, 178, 183 Opportunistic Infections, 28, 183 Oral Health, 105, 183 Oral Hygiene, 4, 5, 7, 15, 105, 183 Organ Transplantation, 5, 183 Osmotic, 139, 183, 197 Osteoblasts, 183 Osteocalcin, 47, 183 Outpatient, 71, 183 Ovaries, 183, 197, 203 Overdose, 33, 37, 46, 58, 107, 133, 163, 183 Oxidation, 137, 142, 154, 174, 183 Oxidative Stress, 45, 183 Oxytocic, 177, 183 P Paediatric, 45, 183 Palliative, 183, 203 Pancreas, 137, 146, 157, 184 Pancreatic, 164, 184 Pancreatic Juice, 164, 184 Panic, 163, 184 Panic Disorder, 163, 184 Paradoxical, 61, 65, 184 Paralysis, 184, 203 Paranasal Sinuses, 184, 198 Parasitic, 173, 184 Parenteral, 52, 89, 93, 94, 96, 184 Paresthesia, 184, 203 Parietal, 182, 184, 185 Parkinsonism, 146, 184 Patch, 30, 99, 184, 205 Pathogen, 29, 184 Pathogenesis, 8, 108, 184 Pathologic, 143, 146, 148, 153, 169, 184, 192, 195, 207 Pathologic Processes, 143, 184 Pathologies, 15, 184 Patient Education, 124, 128, 130, 135, 185 Pediatric Dentistry, 8, 103, 105, 185 Pelvis, 137, 183, 185, 192 Pepsin, 151, 177, 185 Pepsin A, 151, 185

Index 219

Peptic, 185, 201 Peptide, 140, 185, 191 Percutaneous, 5, 185 Perinatal, 46, 92, 105, 185 Periodontal disease, 4, 103, 105, 107, 185 Periodontist, 4, 185 Periodontitis, 105, 165, 185 Peripheral Nervous System, 146, 177, 180, 181, 185, 201 Peripheral Neuropathy, 48, 185 Peristalsis, 158, 185 Peritoneal, 106, 156, 185 Peritoneal Cavity, 185 Peritoneal Dialysis, 106, 156, 185 Peritoneum, 185 Pharmaceutical Preparations, 97, 149, 161, 164, 186, 190 Pharmacist, 27, 186 Pharmacodynamics, 14, 107, 186 Pharmacokinetic, 17, 23, 24, 32, 35, 38, 48, 57, 62, 71, 73, 186 Pharmacologic, 3, 6, 9, 11, 15, 140, 166, 186, 204, 206 Pharmacotherapy, 13, 33, 36, 38, 39, 40, 44, 47, 52, 55, 56, 62, 63, 66, 71, 186 Pharynx, 164, 186 Phencyclidine, 106, 186 Phenotype, 25, 91, 146, 186 Phenprocoumon, 12, 186 Phenyl, 90, 92, 93, 186 Phlebotomy, 9, 186 Phospholipases, 186, 198 Phosphorus, 111, 148, 186 Photosensitivity, 187, 188 Physical Examination, 83, 187 Physical Therapy, 9, 187 Physicochemical, 96, 187 Physiologic, 139, 166, 187, 190, 194, 195 Physiology, 20, 77, 146, 159, 181, 187 Pigmentation, 106, 187 Pilot study, 33, 187 Plants, 139, 144, 151, 157, 165, 168, 178, 182, 187, 196, 204 Plaque, 4, 7, 9, 103, 105, 107, 150, 187 Plasma, 40, 41, 42, 59, 63, 68, 70, 79, 111, 139, 141, 145, 149, 164, 165, 167, 168, 187, 197 Plasma cells, 141, 187 Plasma protein, 139, 187, 197 Plasticity, 11, 187 Platelet Activation, 187, 198 Platelet Aggregation, 187, 203

Platinum, 108, 175, 187 Pneumonia, 36, 153, 188, 205 Poisoning, 58, 106, 158, 171, 179, 188 Polyethylene, 33, 188 Polymorphic, 89, 156, 188 Polymorphism, 51, 70, 188 Polysaccharide, 138, 142, 149, 188 Polytherapy, 15, 40, 188 Porphyria, 9, 186, 188 Porphyria Cutanea Tarda, 9, 186, 188 Porphyria, Hepatic, 188 Porphyrins, 9, 188 Posterior, 144, 150, 158, 184, 188, 196 Postsynaptic, 188, 198, 202 Potassium, 62, 111, 158, 188, 193 Potassium Channels, 62, 188 Potentiate, 77, 188 Potentiating, 91, 92, 188 Potentiation, 77, 189, 198 Practice Guidelines, 120, 189 Prealbumin, 111, 189 Precancerous, 150, 189 Precipitation, 36, 96, 189 Preclinical, 10, 189 Precursor, 143, 154, 158, 159, 160, 181, 189, 205 Prednisolone, 42, 189 Pre-eclamptic, 159, 189 Pregnancy Maintenance, 189 Premedication, 189, 196 Prenatal, 35, 37, 159, 189 Presumptive, 9, 189 Presynaptic, 181, 189, 202 Prevalence, 14, 23, 95, 182, 189 Primitive neuroectodermal tumors, 176, 189 Procainamide, 10, 189 Procaine, 174, 189 Prodrug, 51, 96, 189 Progesterone, 190, 200 Progression, 141, 190 Progressive, 8, 13, 26, 149, 151, 158, 166, 180, 187, 190, 195 Prolactin, 158, 190 Proline, 152, 169, 190 Promethazine, 92, 150, 190 Promoter, 27, 190 Prone, 24, 190 Propanolol, 7, 190 Prophase, 190, 202 Prophylaxis, 7, 39, 68, 189, 190, 195, 207 Proportional, 99, 190

220

Phenytoin

Propylene Glycol, 93, 94, 96, 190 Prospective study, 34, 190 Prostaglandin, 15, 141, 177, 190 Prostaglandins A, 190, 191 Prostate, 191 Prostatitis, 8, 191 Protease, 152, 180, 191 Protective Agents, 148, 191 Protein Binding, 24, 40, 44, 45, 56, 67, 70, 107, 191 Protein C, 99, 139, 140, 144, 183, 191, 206 Protein S, 104, 146, 183, 191 Proteinuria, 8, 52, 191 Protocol, 5, 13, 191 Proton Pump, 182, 191 Protons, 139, 169, 172, 191, 193 Protozoa, 28, 152, 177, 191 Protozoan, 175, 191 Proximal, 157, 189, 191 Pruritus, 157, 190, 192 Psoralen, 9, 192 Psoriasis, 192, 195 Psychiatric, 20, 21, 22, 146, 176, 192 Psychiatry, 20, 24, 31, 39, 40, 52, 53, 56, 192, 200 Psychic, 94, 176, 192, 197 Psychoactive, 192, 203, 208 Psychology, 16, 20, 21, 157, 192 Psychomotor, 76, 93, 148, 192 Psychopathology, 22, 192 Psychosis, 33, 192 Psychotomimetic, 140, 156, 192 Puberty, 105, 192 Public Policy, 119, 192 Pulmonary, 42, 146, 153, 192, 207, 208 Pulmonary Embolism, 192, 208 Pulse, 77, 134, 178, 192 Pyelonephritis, 8, 192 Pyogenic, 8, 192 Pyramidal Cells, 156, 192 Q Quality of Life, 13, 18, 103, 193 Quaternary, 193, 196 Quinidine, 65, 95, 151, 193 Quinine, 106, 151, 193 R Race, 24, 193 Radiation, 99, 106, 141, 160, 162, 163, 171, 172, 193, 200, 205, 208 Radiation therapy, 162, 171, 172, 193, 200, 208

Radioactive, 26, 166, 169, 170, 171, 172, 182, 193, 208 Radioimmunotherapy, 193 Radiolabeled, 172, 193, 208 Radiological, 185, 193 Radiotherapy, 68, 147, 172, 193, 200, 208 Randomized, 12, 18, 32, 33, 56, 64, 159, 194 Ranitidine, 10, 194 Reagent, 33, 194 Reality Testing, 192, 194 Receptor, 9, 21, 27, 30, 73, 137, 142, 151, 152, 156, 158, 161, 162, 172, 181, 194, 197, 198 Receptors, Serotonin, 194, 197 Recovery of Function, 11, 194 Rectal, 33, 194 Rectum, 143, 147, 152, 157, 162, 164, 170, 171, 173, 191, 194, 201 Recurrence, 146, 175, 194 Red blood cells, 161, 188, 194, 196 Red Nucleus, 144, 194 Reductase, 70, 177, 194 Refer, 1, 147, 158, 163, 165, 168, 174, 181, 192, 193, 194, 204 Reflective, 11, 194 Reflux, 112, 164, 194, 201 Refraction, 141, 194, 199 Refractory, 30, 65, 194 Regimen, 16, 159, 186, 194 Regression Analysis, 39, 194 Regurgitation, 164, 167, 194 Relative risk, 22, 137, 195 Reliability, 111, 195 Remission, 146, 175, 194, 195 Renal failure, 17, 111, 195 Renal pelvis, 173, 195 Research Support, 20, 195 Resection, 13, 195 Reserpine, 146, 195 Resorption, 106, 195 Respiration, 178, 195 Respiratory failure, 32, 195 Restoration, 187, 195, 208 Resuscitation, 159, 195 Retinoids, 9, 195 Retrospective, 74, 195 Reversion, 5, 195 Rheumatism, 169, 195, 196 Rheumatoid, 150, 196 Rhinitis, 150, 160, 166, 196 Risk factor, 4, 20, 28, 160, 174, 190, 195, 196

Index 221

Ristocetin, 196, 206 Rod, 151, 196 Root Planing, 5, 196 S Salicylate, 73, 106, 196 Saliva, 196 Salivary, 4, 155, 156, 157, 196, 208 Salivary glands, 155, 156, 157, 196 Saponins, 196, 200 Schizoid, 196, 208 Schizophrenia, 20, 196, 208 Schizotypal Personality Disorder, 196, 208 Sciatica, 57, 196 Scleroderma, 8, 196 Sclerosis, 6, 92, 93, 143, 196 Scopolamine, 92, 196 Screening, 13, 20, 29, 90, 91, 100, 151, 196, 206 Sebaceous, 156, 196, 197 Sebaceous gland, 156, 197 Secretion, 47, 151, 154, 162, 168, 177, 178, 179, 181, 182, 194, 197 Secretory, 182, 197, 202 Sedative, 145, 152, 157, 165, 177, 190, 197 Sediment, 197, 206 Selective estrogen receptor modulator, 197, 202 Self Care, 137, 197 Self Mutilation, 105, 197 Self-Injurious Behavior, 104, 197 Sequence Homology, 12, 197 Serologic, 169, 197 Serotonin, 21, 56, 162, 163, 178, 181, 186, 194, 195, 197, 205 Sertraline, 46, 68, 197 Serum Albumin, 189, 197 Sex Characteristics, 192, 197, 203 Shock, 18, 159, 197, 205 Side effect, 4, 5, 9, 15, 62, 68, 89, 91, 92, 94, 112, 113, 124, 138, 154, 172, 197, 204 Signal Transduction, 15, 198 Silver Sulfadiazine, 88, 198 Simethicone, 7, 198 Sinusitis, 5, 198 Skeletal, 40, 151, 179, 193, 198, 199 Skeleton, 162, 172, 190, 198, 203 Skin Aging, 99, 198 Skull, 154, 198, 200, 202 Small intestine, 158, 168, 169, 171, 198 Smooth muscle, 139, 145, 147, 148, 153, 168, 172, 178, 198, 199, 201 Social Environment, 193, 198

Social Support, 16, 198 Sodium Channels, 18, 193, 199, 206 Soft tissue, 8, 9, 106, 147, 198, 199 Solvent, 93, 94, 161, 166, 183, 190, 199 Somatic, 168, 174, 176, 178, 185, 199 Sound wave, 152, 194, 199 Spasm, 142, 153, 199 Spasticity, 144, 199 Spatial disorientation, 158, 199 Specialist, 125, 185, 199 Specificity, 29, 90, 138, 199 Spectrum, 8, 177, 199 Spinal cord, 20, 29, 143, 144, 147, 149, 150, 176, 180, 181, 185, 199, 201 Spinal Nerve Roots, 196, 199 Spleen, 155, 175, 199 Sporadic, 180, 188, 199 Stabilization, 186, 199 Status Epilepticus, 26, 30, 49, 53, 61, 65, 110, 199 Steady state, 60, 200 Steel, 151, 200 Stereotactic, 5, 200 Stereotactic radiosurgery, 5, 200 Sterile, 8, 200 Sterility, 154, 200 Steroid, 9, 154, 196, 200 Stimulant, 11, 140, 148, 156, 168, 200 Stimulus, 159, 161, 171, 172, 200, 203 Stomach, 7, 83, 97, 112, 137, 145, 157, 161, 164, 168, 173, 175, 179, 185, 186, 194, 198, 199, 200 Stress, 16, 149, 154, 159, 179, 183, 200, 206 Stroke, 11, 59, 85, 93, 118, 200 Stupor, 173, 179, 200 Subacute, 69, 170, 198, 200 Subarachnoid, 29, 63, 167, 200 Subclinical, 69, 170, 197, 200 Subcutaneous, 59, 96, 184, 200 Subiculum, 168, 200 Subspecies, 199, 200 Substance P, 177, 196, 197, 200 Substrate, 12, 15, 18, 201, 205 Substrate Specificity, 16, 201 Sucralfate, 10, 79, 201 Sulfadiazine, 88, 201 Sulfaphenazole, 65, 201 Sun protection factor, 9, 201 Sunburn, 201, 205 Superoxide, 67, 201 Superoxide Dismutase, 67, 201 Suppositories, 7, 33, 164, 201

222

Phenytoin

Suppression, 48, 73, 78, 154, 201 Supraspinal, 144, 201 Supratentorial, 33, 201 Sweat, 156, 201 Sweat Glands, 156, 201 Sympathetic Nervous System, 141, 201 Sympathomimetic, 92, 140, 156, 158, 161, 182, 201, 205 Symptomatic, 6, 18, 26, 202 Symptomatic treatment, 6, 202 Synapse, 91, 138, 180, 189, 202, 205 Synapsis, 202 Synaptic, 20, 26, 30, 91, 181, 198, 202 Synaptic Transmission, 21, 202 Systemic, 15, 52, 69, 114, 146, 148, 150, 161, 170, 172, 189, 193, 196, 201, 202, 208 Systemic lupus erythematosus, 150, 202 Systemic therapy, 150, 202 T Tacrolimus, 5, 33, 202 Talc, 98, 202 Talus, 202, 203 Tamoxifen, 59, 197, 202 Tegafur, 61, 202 Temporal, 12, 26, 140, 168, 202 Temporal Lobe, 12, 26, 140, 202 Teratogenic, 157, 202 Teratogenicity, 37, 202 Testosterone, 17, 140, 194, 203 Tetrahydrocannabinol, 148, 203 Tetrodotoxin, 92, 203 Thalamic, 144, 203 Thalamic Diseases, 144, 203 Theophylline, 7, 10, 42, 65, 95, 106, 107, 112, 157, 203 Therapeutics, 17, 29, 45, 47, 51, 54, 57, 58, 60, 64, 67, 68, 72, 114, 178, 203 Threshold, 25, 161, 169, 203 Thrombin, 187, 191, 203 Thrombomodulin, 191, 203 Thrombosis, 145, 191, 200, 203 Thrush, 105, 148, 203 Thymidine, 203 Thymidylate Synthase, 28, 203 Thyroid, 7, 203 Thyroxine, 139, 203 Tibia, 37, 162, 203 Ticlopidine, 65, 203 Tin, 184, 185, 187, 204 Titre, 67, 204 Tolerance, 50, 151, 204 Tone, 145, 183, 199, 204

Tonic, 13, 78, 93, 99, 149, 151, 177, 204 Tooth Preparation, 137, 204 Toothache, 5, 204 Topical, 9, 31, 71, 73, 88, 98, 99, 150, 161, 169, 204 Topoisomerase inhibitors, 172, 204 Topotecan, 77, 204 Toxic, iv, 6, 46, 63, 72, 100, 144, 151, 153, 157, 160, 166, 180, 181, 204, 206 Toxicity, 11, 24, 28, 38, 53, 54, 60, 61, 63, 69, 72, 74, 78, 158, 181, 196, 201, 204 Toxicology, 35, 45, 49, 58, 59, 65, 76, 77, 78, 105, 120, 204 Toxin, 203, 204 Toxoplasmosis, 201, 204 Trace element, 67, 204 Trachea, 147, 186, 203, 204 Traction, 151, 205 Transdermal, 99, 205 Transduction, 198, 205 Transfection, 146, 205 Translation, 140, 205 Transmitter, 144, 158, 172, 176, 177, 182, 205 Transplantation, 40, 52, 68, 151, 205 Trauma, 29, 66, 72, 93, 104, 145, 161, 167, 194, 203, 205 Triad, 8, 205 Tricyclic, 6, 18, 56, 89, 205 Trigeminal, 4, 5, 50, 109, 112, 205 Trimethoprim-sulfamethoxazole, 33, 205 Tryptophan, 152, 197, 205 Tuberous Sclerosis, 6, 205 Tyramine, 178, 205 U Ulcer, 9, 105, 155, 158, 177, 201, 205, 206 Ulceration, 155, 173, 205 Ulcerative colitis, 9, 171, 205 Ultraviolet radiation, 198, 201, 205 Unconscious, 134, 141, 169, 206 Urea, 92, 146, 201, 206 Uremia, 195, 206 Ureters, 173, 206 Urethra, 191, 206 Uric, 139, 145, 166, 206 Urinalysis, 8, 206 Urinary, 14, 57, 145, 151, 154, 160, 170, 182, 196, 206, 208 Urinary Retention, 145, 206 Urine, 8, 9, 26, 145, 146, 157, 167, 170, 173, 182, 191, 195, 206

Index 223

Uroporphyrinogen Decarboxylase, 188, 206 Urticaria, 150, 206 V Vaccine, 191, 206 Vagina, 148, 206 Vaginitis, 148, 206 Valproic Acid, 12, 13, 14, 24, 44, 47, 79, 99, 206 Vancomycin, 95, 111, 206 Varicose, 173, 206 Varicose Ulcer, 173, 206 Vascular, 8, 49, 139, 148, 156, 170, 172, 206, 207 Vasculitis, 69, 207 Vasoconstriction, 161, 207 Vasodilator, 142, 158, 168, 181, 207 VE, 59, 207 Vein, 84, 143, 172, 182, 186, 207 Venous, 43, 143, 145, 167, 173, 191, 204, 206, 207 Venous Thrombosis, 145, 204, 207, 208 Ventricle, 140, 144, 168, 192, 207 Ventricular, 46, 207 Verapamil, 98, 99, 207 Vertebrae, 171, 199, 207 Vertigo, 157, 207 Vesicular, 168, 177, 207 Veterinary Medicine, 76, 119, 207 Villous, 149, 207

Viral, 18, 205, 207 Virulence, 204, 207 Virus, 32, 44, 105, 144, 160, 171, 187, 205, 207 Vitiligo, 192, 207 Vitro, 15, 18, 207 Vivo, 11, 18, 207 Volition, 172, 207 Voriconazole, 38, 207 W Warfarin, 6, 7, 10, 15, 17, 18, 19, 112, 207 Wart, 17, 208 White blood cell, 8, 141, 173, 175, 179, 187, 208 Windpipe, 186, 203, 208 Withdrawal, 5, 26, 71, 77, 78, 208 Wound Healing, 66, 73, 88, 208 X Xanthine, 139, 208 Xanthine Oxidase, 139, 208 Xenograft, 141, 208 Xerostomia, 106, 208 X-ray, 6, 89, 162, 163, 172, 182, 193, 200, 208 X-ray therapy, 172, 208 Y Yeasts, 148, 163, 186, 208 Z Zymogen, 191, 208

224

Phenytoin