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."

This series is intended particularly for young doctors working in hospitals and in primary care and for those involved in training them. The series has been designed to cover growing points in medicine and the authors have been chosen, not just because of their expertise, but also because they are working both in hospitals and the community and are thus sensitive to the problems and needs of doctors in both areas.

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."

In recent years, papillomaviruses in general and human papillo maviruses in particular have been recognized as possible agents of important diseases, including some forms of human cancer. The purpose of this book is to present a concise panorama of the pre sent status of knowledge of this topic. This knowledge is as impor tant to molecular biologists and virologists as it is to clinicians and pathologists. To bridge the gap among these diverse groups of investigators, we conceived of a book covering a broad spectrum of the basic scientific, clinical, and pathological aspects of diseases associated with papillomaviruses. Although the principal thrust of this book is directed at human papillomaviruses, fundamental knowledge of animal viruses is essential to the current understand ing of the molecular mechanisms of cell transformation. For this reason, a chapter on animal viruses has also been included. Some of the experimental work having to do with the elucidation of transformation and other aspects of interaction between the virus and the cell cannot be based on human papillomaviruses because of a lack of suitable experimental models. Hence, some of the chapters dealing with fundamental aspects of viral molecular biol ogy are based on animal models. We were very fortunate in having persuaded a number of distin guished colleagues to contribute to this work."

The control of cancer is at once a major public health problem and a problem of fundamental biologic interest. As a result of technologic developments and new insights in the realm of molecular biology, new and important approaches to an understanding of neoplasia are now possible. Several aspects of neoplasia are clearly of microbiologic interest, including the role of viruses in the etiology of cancer, control of the immune response to tumor cells, and the susceptibility of tumor-bearing hosts to overwhelming infection as a result of immuno deficiency. Recent advances in these areas led us to organize this symposium, and, through this publication, to record some of the progress being made in laboratories around the world in understanding some of the basic aspects of the cancer problem. This symposium was held as part of the commemoration of the twentieth anniversary of the Waksman Institute of Microbiology. Dr. Waksman's devo tion to the study of the smallest forms of life and the commitment of the Waksman Institute to the free pursuit of knowledge are the underpinnings of the institute's research eHorts in the broad area of microbiology, including the problem of neoplasia. It is of interest to note that actinomycin, one of the earliest antibiotics discovered in Waksman's laboratory, was also one of the first compounds found to be clinically useful in the treatment of certain types of cancer."

In the last fifty years dramatic progress has been made in the under standing of skin and skin diseases. Although we are still someway off understanding the ultimate causes of such disorders as psoriasis, atopic dermatitis and the congenital disorder of keratinization, we now have considerable information on the physiological disturbances in various diseases. This has permitted and encouraged a rational approach to treatment. The successful use of antimitotic agents, immunomodulators and retinoids may be cited as examples. A major reason for this im provement may be the fact that researchers accept models for the in vestigation of skin diseases. Increasing numbers of them have become available in the past years. So many have been described that it is doubtful whether anyone researcher is aware of all the other models described - even in his own field of interest. This book is a challenge for those involved in the study of skin and its disorders to use the sundry models of skin that have proven helpful. It would be impossible for this work to be all-embracing but it is hoped that the choice of models offered in this publication will be stimulating and helpful in the solution of knotty skin questions. April,1986 Ronald Marks, Cardiff Gerd Plewig, DUsseldorf Table of Contents In Vivo Models Human Model for Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 L. C Brummitt, W. J. Cunliffe, G. Gowland Models to Study Follicular Diseases l3 G. Plewig Models for Wound Healing. . . . . . . . . . . . . . . . . . . . . . . . . 24 R. Marks, D. Williams, A. D."

Recent progress in the fields of pharmacology and immunology has provided us with new possibilities for treating dermatological diseases. This book reviews the most important immunosuppressive and immunostimulatory drugs and gives helpful, practical information on the treatment of various dermatoses, including autoimmundiseases, atopic dermatitis, psoriasis, vasculitis, contact dermatitis, pyoderma gangrenosum, infectious diseases, and neoplasms of the skin - in particular, malignant melanoma.

The induction of immune responses against tumor cells by vaccination is rapidly evolving as a therapeutic modality with new potentials for the treatment of cancer. It is based on the fact that our immune system can identify tumor cells and, once activated, is capable of developing specific immunity against the neoplastic cells. Numerous observations and intense research clearly document the major contribution of the immune system to the prevention of cancer. And there are many re ports of patients suffering from malignant melanoma or other tumors who mount a spontaneous immune response against their tumor cells that results in tumor regression. Based on the recent advances in our understanding of the compo nents of our immune system, their interactions and the regulation of immune responses, we are now able to design vaccination strategies that induce or enhance cell-mediated immunity against tumors. A ma jor advancement came with the identification and characterization of relevant tumor antigens, which are suitable target structures for anti-tu mor immune response. First clinical trials using such vaccine strategies have yielded encouraging results in patients. However, in spite of many reported cases of successful therapy of cancer by vaccination many patients still do not experience relief after such treatments. These initial clinical trials and the accompanying investigations have revealed a number of important results that indicate the direction of future re search and development in the field.

There is no doubt among experts that the prevalence of allergic diseases has increased in many industrialized countries in recent years. The rea sons for this increase are unknown; only suppositions exist. Many people focus on environmental influences. However, the assumption that air pollution alone is responsible for this increase seems to be too simple: many other influences, including the genetic predisposition of individual patients, allergen exposure, and possibly socioeconomic factors, also have to be taken into consideration. Although our understanding of the complex mechanisms of allergic diseases has considerably improved thanks to the progress made in ex perimental immunology and allergology, we still have a long way to go before this scientific knowledge is translated into new therapeutic mo dalities. For this reason, the scientific community welcomed the gathering of scientists from very different disciplines and different parts of the world at an international symposium, "New Trends in Allergy IV" together with "Environmental Allergy and Allergotoxicology III" in Hamburg in 1995. This volume contains the invited papers, covering a wide range from basic science to practical clinical diagnosis and therapy. A further unique feature of this event was the concomitant first official workshop of the Environmental Pollution and Allergy Committee of the International Association of Allergy and Clinical Immunology (IAACI), at which the state of scientific knowledge in this field was defined and formulated."

Because skin blisters are the initial manifestation of epidermolysis bullosa (EB), patients invariably present to the dermatologist for diagnosis and treatment. However, EB is a systemic disease whose management requires input from clinicians in virtually all fields of medicine, including pediatri cians, surgeons, dentists, gastroenterologists, hematologists, otorhinolaryn gologists, dietitians, and physical therapists, to name a few. Because EB is a rare disease, few clinicians are familiar with it, and many recoil at the pros pect of caring for individuals covered with blisters caused by a disease they know little about. For patients, insult is thus added to injury and they feel abandoned, neglected, and frustrated. One way to remedy this deplorable situation is to provide clinicians with a compact source of information de tailing the principles of EB diagnosis and treatment. This text seeks to fulfill this role. From 1986-1991, The Rockefeller University Hospital has been the co ordinating center of the National EB Registry. Supported by The National Institutes of Health, this Registry consists of four university centers* commit ted to collecting clinical data concerning diagnosis, treatment, and epidemio logy on all American EB patients. As of April 1992, nearly 1,799 EB patients have enrolled nationwide. The Registry is now in its second five-year phase of operation."