Proceedings of the 5th Biannual International Meeting on Angiogenesis: From the Molecular to Integrative Pharmacology, held July 1-7, 1999, in Crete, Greece. Angiogenesis, as a vastly complex biological process, has challenged researchers from all basic scientific disciplines, including pharmacology, biochemistry, physiology, embryology and anatomy. The significance of this phenomenon for the study of disease states has also interested clinicians from a number of specialist fields. This multidisciplinary work reflects the growth of awareness of concepts such as angiogenesis based therapy, the enormous therapeutic and commercial potential of which has attracted major research and investment in recent years. This volume, which aims to bridge the gap between basic and clinical methodology and understanding, presents the most up-to-date developments in this field.

In the past two decades, considerable interest in skin cancer has developed in the public and scientific communities. There may have been several reasons for this: - The rise in the global incidence of cutaneous cancers - New molecular biology techniques resulting in a better understanding of pathogenesis and improved diagnostic procedures - The advent of new pathological entities, e. g. , the endemic form of Kaposi's sarcoma - A constantly increasing range of therapeutic modalities, providing even more efficacious treatment and manage ment of skin cancers As N. E. Fusenig describes in the first chapter of this volume, basic research is only beginning to unravel the complex mechanism involved in cellular dedifferentiation and tumor progression. Progress is dearly needed, especially in dermato oncology, where the rise in the incidence of epithelial tumors has inflated the overall skin cancer incidence. The incidence of tumors of the skin exceeds that of all other neoplasias in humans, with recreational sun exposure being a suspected primary cause. Several studies on the effects of UV radiation have been included at the beginning of this volume. Even the role of long wavelength UV (UVA) has become a focus of research activities. The main concern is that the low carcinogenicity of UVA, in comparison to UVB, may be outweighed and exceeded in its effects by increased UV A exposure, e. g.

With chapters from experienced and internationally renowned contributors holding positions in research, industry, and clinical practice, this is the fifth edition of what has become the standard reference for cosmetic scientists and dermatologists seeking the latest innovations and technology for the formulation, design, testing, use, and production of cosmetic products for the skin. *Offers in-depth analysis of specific topics in cosmetic science and research *Presents the latest in international research and its translation to practice *Gives an indispensable guide to a hotly competitive area for research and practice

Androgen Receptors is the most comprehensive and up to date volume on the topic, including discussions of the basic mechanisms of androgen-androgen receptor actions, their roles in the androgen-related diseases, and their potential clinical applications. Key topics covered include: -The discovery and cloning of the androgen receptor; -Androgen receptor coregulators; -Androgen related genes and their consensus DNA response elements; -Basic mechanism of action including functional analyses, cellular localization and phosphorylation studies; -Cross-talk to other signal transduction systems; -The recent connections of androgens to women's diseases, such as osteoporosis and ovarian cancer. This book is of interest to students, basic scientists, and clinicians as both a study guide and reference of research in the androgen field. It could also be used as an advanced level text in endocrinology, urology, OBGYN, or oncology.

Not since the 1965 pUblication of Skin Bacteria lind Their Role in Infection has our knowledge of clinical skin microbiology been reviewed and sum marized. In the more than a decade and a half since that publication, we have seen a careful reevaluation of the ideas and information current in 1965 and the development of important new discoveries and information. This volume, Skin Microbiology: Relevance to Clinical Infection, reviews developments in the field since 1965 and summarizes the current state ofthe art in thirty-six carefully prepared chapters. Emphasis is on the clinical per spective rather than straight microbiology, although we include enough of the latter to put the clinical aspects in a proper scientific context. The authors contributing to this volume represent a cross section of authorities in the many specialty areas that contribute to our knowledge of skin microbiology. They include investigators in microbiology, infectious disease, epidemiology, surgery, pediatrics, and dermatology. Significant ef forts have been made to minimize repetition and overlap in the various chapters. In some cases, however, information is deliberately repeated in order to provide for the reader a necessary frame of reference. We hope that this volume will be of value to dermatologists, microbio logists, pediatricians, surgeons, public health workers, nurses, and others in volved in the diagnosis and treatment of dermatologic problems caused by bacteria. The editors acknowledge with appreciation the assistance of Drs. A. Allen, F. Marzulli, F. Engley, G. Hildick-Smith, A. Kligman, M. Bruch, H. Eiermann, and D. Taplin."

With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent chronic therapy (8-15 months), substantial plasma levels of both unchanged drug and main metabolite (corre sponding carboxylic acid) were observed up to 140 days after cessation of the therapy. An apparent half-life of elimination of 80-100 days can be calculated. The drug appears to be stored at some yet unknown storage site. Investigation of metabolism of Tigason in rats and humans revealed 19 different bio transformation products thus far, most of them appearing in the urine in low amounts (20010 of dose). A few of them (mainly the acid Ro 10-1670) after conjugation to glucuronic acid are excreted in the bile in high amounts (60-80% of dose). No drug appeared unchanged in the excreta after i. v. administration to rats. References 1. Bollag W (1971) Effects of vitamin A acid (NSC-122758) on transplantable and chemically-induced tumors. Cancer Chemother Rep 55:53-58 2."

The skin, uniquely positioned at the interface between the human body and the external world, plays a multifaceted role in the expression of cancer. Primary skin cancer is the most common cancer afflicting mankind and is rising in inci dence, despite the fact that it is often preventable. Besides primary cancer, the skin may show direct and indirect evidence of internal cancer, thus serving as a window to the body for both laymen and physicians alike. In addition, the acces sibility of the skin is useful for the study of carcinogenesis as well as cancer treat ment options. lowe much of my interest in skin cancer to Dr. Leon Goldman, the father of dermatologic laser surgery, and to Dr. Edmund Klein, the father of modern immunotherapy. We, at the Roswell Park Memorial Institute, were indeed for tunate to have a wealth of patients available for study. Many of the illustrations used in this book were of my patients at the Institute, and I kindly thank the fol lowing publications and their respective publishers for allowing me to reuse some of my photographs, most notably: Cancer Medicine (2nd edition), Journal of Surgical Oncology, Journal of the American Academy of Dermatology, Archives of Dermatology, Cancer, and Journal of Dermatologic Surgery and Oncology. We are very fortunate in this work to have some of the world's foremost authorities in their areas as contributors, such as Drs. Zackheim, Lambert, J.W. Trimble, J.R. Trimble, Jackson, Crutcher, Mashberg, Wick, Sidell, F. Helm, G.

Radiation therapy of cutaneous cancers and other dermatologic disorders is not covered adequately in many current textbooks of dermatology and radiation oncology. This book is intended to fill that gap. Both text and illustrations are oriented toward the practical aspects of radiation therapy. The beginner will find a concise introduction to physical and biological principles, selec tion of radiation factors, dose definitions, indications for treatment, and radiation seque lae. The experienced dermatologist and radiation oncologist will find a detailed discussion of specific indications for various radiation techniques in different body regions. A special effort was made to add pertinent references to the world literature for those who wish to pursue particular topics still further. We have tried to include all major American and European publications of the last 20 years in our bibliography of more than 500 refer ences, and we also have attempted to review the most important scientific papers on prin ciples and practice of ionizing radiation therapy in a constructive way. We are grateful to Professor Gorson, Dr. Breneman, and Professor Lindel6f, who generously contributed chapters in their areas of expertise despite their many other com mitments."

Amidst the innumerable articles and books on plastic and reconstructive surgery, a thorough and extensive study of the history of free skin grafting was still missing. This omission has now been rectified by Dr. Klasen. This book is an expansion of a M.D. thesis, written at the State Universi- ty of Groningen, The Netherlands, and was guided by Professor A. J. C. Huffstadt, plastic surgeon, and Professor D. de Moulin, medical historian. Professor T. Gibson kindly revised the manuscript and wrote the epilogue. But, as Goethe put it: "nur ein Teil der Kunst kann gelehrt werden, der Kunstler macht das Ganze" ("only a part of the art can be taught, the artist makes the totality"). The author, Henk Klasen, is a remarkable man. As a general surgeon, he devotes all his interest and skills to traumatology and problems of phys- iology and pathophysiology in surgery. With such talents it is natural that he also works parttime as one of the coordinators ofa modern burn unit. Among his hobbies are love of antiques and old books. This historical inclination has induced him to write the present book, in which he vividly describes the development of free skin grafting in its rel- evant theoretical and practical aspects. His elaborate study has resulted in an excellent reference book which at the same time provides enjoyable reading, once again demonstrating the value of history in understanding the present. A. J. C. HUFFSTADT, M.D.

Interest in the etiology of malignant melanoma has increased enor mously in the last 10 years, after it was realized that the incidence of the cutaneous form of the disease was rising. Treatment of the disease has not improved dramatically, and our best hope for curtailing the rise in mortality and morbidity from the disease appears to be primarily through early detection and, per haps in the future, through prevention. It is thus very important for the medical community to be able to recognize individuals and groups at high risk of the disease because of either familial and con stitutional factors and lifestyle or exposure to environmental risk factors. This book, arising from a meeting held in Vancouver in 1984, pro vides a summary of the latest findings amo ~ Caucasian popula tions along with perspectives on the most im, Jrtant environmental risk factors identified to date. Comparison of results from the four major analytic studies presented here also demonstrates that a num ber of factors implicated in other common cancers are probably not related to the incidence of melanoma. These include smoking, alco hol consumption, and for the most part, diet. The Vancouver conference was sponsored by the Cancer Control Agency of British Columbia, and was financially supported by Health and Welfare Canada (6610-1429-50), the Northern Califor nia Cancer Program (NCCP), Miles Laboratories (Canada), Bristol Myers Laboratories (Canada), and Plough Canada Inc.

More than 10 years ago, I had the chance to visit the university hospital in Munster, Germany. At the outpatient clinic there, I accidently met a young dermatologist who was devoted to the study of the quantification of irritated skin during his busy daily clinical work. I sensed immediately that this Dr. P. Frosch was conducting his research with the ideals and enthusiasm which were so familiar to me. Soon we found that we shared a similar past experience; we both had begun our careers in dermatological investigation with the same mentor. For me it was more than 25 years ago that I first met Dr. Kligman, Professor at the University of Pennsylvania in Philadelphia, USA. I reminisced that I had been greatly shocked by his initial question ''As a dermatologist, do you want to study living or dead skin?" because, at that time and even today, whenever we cannot collect enough information about the skin with the naked eye, it is invasively removed is common practice to histologically examine a skin sample that from living tissue. Many dermatologists still would never think of studying the living intact skin itself noninvasively with the aid of existing advanced technologies to assess its structural and functional properties. At that time Dr. Kligman intended to build up a system of evaluating the skin from various aspects, using methods that had been unduly neglected in the past and introducing various technological instruments.

The epididymis has great significance in the reproductive biology of the male and it is gaining recognition as an organ worthy of study in its own right - where the secretory and absorptive activities of one tissue (the epithelium) profoundly modify the function of another (the spermatozoon). Apart from cases of epididymal agenesis or physical blockage, however, it is not yet known to what extent mal functions of the epididymis contribute to "unexplained" male infer tility, but its importance as a target for antifertility agents in the male is now widely appreciated. This monograph evolved from two lectures on epididymal func tion given at the National Research Institute for Family Planning, Beijing and the Sichuan Provincial Family Planning Research Insti tute, Chengdu, China in 1983. In order to stress for this audience the central importance of the epididymis in fertilisation, and so highlight its potential for attack by antifertility agents, the talks attempted to put the epididymis in reproductive perspective by stressing the func tional development of the sperm cells during their sojourn in the epididymis, rather than merely listing the changes observed in them."

Mohs surgery is a highly effective treatment for certain cutaneous and oral pharyngeal cancers. The procedure allows for the precise and complete removal of cancers while preserving significant amounts of normal tissue. Through the presentation and orientation of the specimens' complete surgical margin on pathology slides, the location of tumor foci and other relevant findings can be correlated with their locations on the surgical wound. The ability to create perfect slides for histological examination lies at the core of effective Mohs surgery. These procedures have a 99 per cent cure rate for certain cancers when implemented correctly. This book describes the methods the dermatologist, pathologist, or technician can use to optimize the Mohs technique and produce the highest-quality slides and highest cure rates possible.

Urticaria is a vexing problem, to the patient who teachers who have stimulated my interest and helped suffers from the annoying pruritus and the fear oflife me to understand the basic and clinical aspects of mast threatening reactions, to the physician who faces the cell-related problems is long. I would like to specifi challenge to find the cause of the eruption and to cally mention J.N. Fink during medical school train control the symptomatology, and to the scientist who ing in Milwaukee, J.R. Pomeranz and R.W. Belcher is asked to explain the process that elicits tissue during dermatology residency in Cleveland, L.M. swelling at the cellular and molecular levels. Lichtenstein and P. Norman during a research fellow The last thorough treatise on urticaria was the ship at the Department of Clinical Immunology and superb monograph by R. P. Warin and R.H. Champion, Allergy at Johns Hopkins University in Baltimore, and published more than a decade ago. Since then, there E. Macher at the University Clinics in Miinster where have been major advances in the field. This holds much of what I have learned in the past could be particularly for the clinical aspects of anaphylactoid broadened through further basic research and clinical reactions, the urticarial vasculitis syndrome, and the experience.

Herpes Simplex Virus is the fifth monograph to be published in the Bloomsbury Series of Clinical Science. It provides an authoritative review of the key issues related to this common clinical problem. The characteristics of the virus, its epidemiology and the diag nosis and management of the various forms of infection are all considered. Adrian Mindel is an international authority on this subject; he joined the Academic Department of Genito-urinary Medicine at the Middlesex Hospital in 1980 and has been actively involved in HSV research since that time. His major research interests include the epidemiology and treatment of genital herpes, the epidemi ology of neo-natal herpes and the many and varied features of HSV infections in immuno-compromised patients. The continuing aim of the Bloomsbury Series is to identify the growing areas of clinical research and relate these to current and future medical practice. In Herpes Simplex Virus such aspirations have been successfully achieved. London, May 1989 Jack Tinker Preface There has been considerable interest in herpes simplex viruses (HSV) over recent years. Amongst the many reasons for this are the introduction of safe and efficacious therapy, the recognition that HSV may cause life-threatening infections in neonates and immunocompromised patients, the observation that genital herpes is one of the commonest viral sexually transmitted diseases and the possible association of HSV with cervical cancer."

The first edition of "Testosterone: Action, Deficiency, Substitu tion" was published in 1990. Since then our understanding of the hormone that turns males into men has tremendously increased. Therefore, the editors felt that a second extended edition of the book is warranted in order to summarize established and recent findings in the field and to present the reader with an up-to-date is reflected by the textbook. The increased mass of knowledge growth of the volume from 14 to 20 chapters. In the updated edition the biochemistry and metabolism of androgens have been complemented by extensive information on the molecular biology of the androgen receptor and its disorders. The key role of testosterone in spermatogenesis is now better de fined. We have a more complete understanding of the psychotro pic effects of testosterone and know so much about the different target organs and functions that individual chapters deal with testosterone and the prostate, lipids and the cardiovascular sys tem, hair, bones and muscles. The general chapter on pharmacol ogy and clinical uses of testosterone, in particular in male hypo gonadism, is extended by pharmacokinetic studies on testoster one preparations and individual substitution modalities using testosterone esters as well as implants and advanced trans dermal applications. The physiologic basis and possible clinical applica tions of testosterone in non-gonadal diseases, in male senes cence, in hormonal male contraception and in transsexuals are discussed. The last chapter describes the role of "investigative" steroid biochemistry applied to tracking anabolic steroid abuse."

Measuring the Skin presents all techniques devoted to non-invasive normal or diseased skin measurement. As opposed to other books, this text embraces old and new validated techniques for all skin suborgans and functions, and is ideal as a small encyclopedia since it provides the answer to any question concerning skin measurement. Within each chapter, the meaning of the obtained parameters is highlighted so that the user is able to interpret the results correctly, and each technique is discussed to help select the most appropriate one for each special case. Another novel feature is that the book bases the skin investigation on the physiology and anatomy. A compendium of current knowledge on the structure or function dealt with precedes each chapter. The book may also be used as a research tool. This comprehensive text contains an innovative and unique list of more than 400 physical and biological skin constants, which are all referenced. The clinical dermatologist will also find this text useful as some chapters contain valuable maps and are devoted to clinical scoring of current skin diseases. Measuring the Skin is a resource for all those interested in or already dealing with the skin.

Aspects of Lyme Borreliosis is a comprehensive scientific presentation of virtually all aspects of lyme borreliosis. It starts with a concise history of lyme borreliosis and its causative agent, Borrelia burgdorferi. The morphological and biological characteristics of B. burgdorferi are presented, followed by outlines on the ecology and histopathology of LB.The various aspects of the clinical manifestations of LB are systematically dealt with, starting with a clinical overview. A special chapter covers the microbiological diagnosis. After a presentation on the susceptibility of B. burgdorferi in vitro and in animals against a great variety of antibiotics, a thorough discussion on the treatment of LB including criticalremarks follows. The book closes with a chapter on the epidemiology of LB.

Wc have felt for some years that an atlas of paediatrie dermatology merired a place in the world dcrmatologicallitcrature. Non-dermatologists find skin conditiom difficult to describe and diagnose and this may bc cvcn mare difficult in children. Wc usually rely on the paTents for a history in childrcn, although many conclitions can bc spur dtagnoses. In this atlas wc have med to illustrare cOllditions seen regularly 111 our dinics as weIl as some seen mare rarely but which arc nevercheless important to recognize. Wc have limired the number of illustrations tn order to producc a realistically-priced book and thus it has not always becn easy to decide what to indude and whae to omu. Howevee, wc hope that wc havc produced a reasonably comprehensive work. We hope that this atlas will have a wide appeal both at home and abroad. It is a book either to read or to browse through. It is intended for senior medical students, family practitioners, and for trainees both 111 dermatology and in paediatrics. We would like it acttlally taken to skin clinics to be avatlablc for instant pcrusal, and to bc on hand in the paediatric ward. Wc have said comparatively little about treatment because this alters regularly and often varies in different centres and bccause we do not think that an atlas is the place for this."

The morphological behaviour of leucocytes* leaving the blood has been studied for more than a hundred years and can be described in some detail, but the mechanisms involved are for the most part still unclear. Following an inflammatory stimulus, dy- namic changes occur in small blood vessels near the inflamed site and are followed by margination of leucocytes and by their adherence to the endovascular surface of endo- out of the vessel in the gaps between endothelial thelial cells. The leucocytes migrate cells and move towards the noxious stimulus, directed presumably by chemotactic gra- dients. Having reached the gradient source, they may engage in phagocytosis, killing and digestion of micro-organisms or of damaged tissue. In this review, we deal with the adhesive properties of leucocytes, which have US1,l;ll- ly been measured in vitro, and with their possible relevance to the leucocyte-endo- We also deal with the locomotion of leucocytes, its machinery thelial cell interaction.

R. MARKS Biology has become a 'numbers game'. The advantages of being able to grade changes in tissue, submit results to statistical analysis and accurately record biological phenomena make measurement essential. This is as true for the various disciplines in applied biology as it is for the more esoteric aspects ofthe subject. Regrettably, sk in biologists until recently had not seized the opportunities that the availability of their tissue of interest afforded and fell behind in the exploration of measurement techniques. Probably this resulted in part from the mistaken sentiment that 'to see is to know'. It also originated from the complexity ofthe skin which. as a closely interwoven mixture oftissue types. makes assessments technically difficult. However, we are optimistic about the future. The International Society for Bioengineering and the Skin was formed in Cardiff in ] uly 1979 in response to the wishes of the delegates who had attended the first International Symposium on the subject in Miami in 1976 and the second in Cardiff 3 years later. This volume is the proceedings of the Cardiff meeting. We believe that it demonstrates the brave efforts and variety of new ideas that characterise the studies of scientists who realise the importance of blending the phYSICal sciences with skin biology.

Dermatology is a complex and puzzling world of itching bumps, pim ples, and rashes. The multitude of clinically distinct skin diseases, their frequently unresolved pathogenesis, and the exponentially in creasing amount of scientific information add to the confusion about skin diseases. The great prevalence of skin diseases makes them an urgent priority for intensive research effort, and although many scientists and academic clinicians are vigorously trying to uncover we are only at the very brink of understanding the etiol their secrets, ogy of most dermatoses. The principle mechanisms of general organ pathology (physical, chemical, microbial, ischemic, degenerative, and neoplastic disturb ances) are believed to be relatively well understood. In contrast to skin pathomorphology, however little is known regarding the bio chemistry and physiology of dermatoses. The difficulty in under standing skin diseases may be overcome partially by finding biome dical simplifications, and the concept of "oxidative injury in dermatopathology" is just such a simplification. It should, of course, always be kept in mind that no single mechanism alone can explain the pathogenesis of a disease and that there may be a danger of over looking other important biological determinants."

Substances that are applied to the skin to heal it, make it feel better or improve its appearance, have much in common. They can all do damage to the skin as well as perform the task for which they were designed. They and the substances they contain are all absorbed through the skin to a greater or lesser extent. In addition, all these agents are constructed in the same general way. For these reasons it seems odd and uneconomical to consider topical pharmaceuticals, toiletry products and cosmetics separately. This was the reasoning behind the holding of a small symposium of workers involved with one or another aspect of the formulation of substances destined for application to the skin. Several aspects of the subject are covered in this book which is based on the symposium and the contents should be of interest to all who are concerned with the prescription, assess ment or formulation of topical agents. 9 1 Acne Caused and Treated by Topical Agents W. J. CUNLIFFE The four main aetiological factors involved in the development of l acne are (1) an elevated sebum excretion rate ; (2) ductal hyper 3 keratinization 2; (3) an abnormality of microbial function ; (4) host 4 inflammatory response * Although opinions differ on both sides of the Atlantic, most authorities in the United Kingdom believe that increased sebum excretion rate is the main drive to acne, there being a definitive relationship between the severity of the acne and the seborrhoea of this disease.

This text was designed for the physicians, nurses, technical personnel, and staff members of medical facilities using lasers for surgical, therapeutic, and diagnostic purposes. The objective is to provide an understanding of the potential health and safety hazards associated with the use of medical laser systems and the precautions needed to use them safely. To do this, it is necessary to have an awareness of applicable standargs and regula tions that apply to laser use. This book is not intended as a substitute for the American National Standards Institute (ANSI) Z-136. 3, "Safe Use of Lasers in Health Care Facilities," but to facilitate its implementation as well as the implementation of the many other related regulations and guidelines that are pertinent. These other regulations include the Medical Device Amendments to the Food and Drug Act, the Federal Laser Product Performance Standards issued under the Radiation Control for Health and Safety Act, and applicable regulations of the Occupational Safety and Health Administration (OSHA). The text is organized to provide first an overview of laser hazards, laser surgical applications, and laser biological effects. General safety control measures and safety standards are then presented. Because laser tech nology is rapidly evolving, these general guidelines will allow safe use of new laser systems as they become available. Finally, specific safety guide lines and precautions are provided for specialized laser applications in the different health care specialties."