Professor George Fegan is a world authority on the use of sclerotherapy for the treatment of varicose veins. His technique for injecting varicose veins is regarded by many to be the best method for achieving success with sclerotherapy. Professor Fegan first published his method in 1963. This book is an update to his previous work and describes his method step by step as well as relevant information on the anatomy, physiology, pathology and investigations of varicose veins. Sclerotherapy is finding its place as an effective weapon in the phlebologist's armamentarium, and its indications are becoming clearer. All involved in the care of patients with venous disease will find this an invaluable read.

This book offers a unique insight into the world of cutaneous lymphomas. In addition to the case description it gives the clinical, histological, and in most cases also the phenotypical features and the results of molecular techniques. A commentary puts the observations into the context of cutaneous lymphomas. High quality pictures accompany this exceptional collection of rare and unusual cases. These will interest dermatologists, oncologists, pathologists and hematologists.

The international symposium "New Trends in Allergy," held in Munich from July 13 to 15, 1990, brought together for the third time since 1980 some of the most experienced researchers working in the field of allergy. This volume comprises the papers presented at this meeting. All over the world, and not merely in the industrialized countries, allergy is becoming a cause of evermore serious diseases. In recent years, research in the field of allergy has provided numerous impor tant and fascinating results extending our knowledge considerably. Despite the new insights into basic mechanisms of allergic reactions, improved diagnostic methods, and new therapeutic approaches, how ever, many questions remain to be answered, including: Are allergies really increasing in frequency? If so, what are the reasons? Especially, does environmental pollution playa role? Which factors influence IgE synthesis? Can the IgE immune response be switched off? Does the nervous system interact with allergic reactions? If so, what are the mechanisms? Are new approaches in allergy prophylaxis and allergy therapy effi cient? What measures have proven useful and deserve to be employed in daily practice? In this volume, these questions and other current topics are dealt with. As each issue is covered by authors competent in the respective fields, the result is an extensive and critical review of the state of the art. Going through these papers, one comes to the conviction that allergy research is a multifacetted, explosively expanding, most stimulating field of work."

During the last 40 years, the study of the biological basis of aging has progressed tremendously, and it has now become an independent and respectable field of study and research. The essential cause of aging is molecular damage that slowly overwhelms cellular and organismic defense, repair and maintenance systems. In recent years, a wealth of highly sophisticated research has transformed this idea from a credible hypothesis not only to a major theory, but essentially to accepted knowledge. Aging at the Molecular Level examines the key elements in this transformation.
Bringing together contributions from an international team of authors, this volume will be of interest to graduates and postgraduates in the fields of medicine and nursing, researchers of different aspects of biogerontology and those in the pharmaceutical, cosmeceutical, nutraceutical and health-care industry.

The two organs of the body most accessible to examination are the eye and the skin and its appendages. That is why, it is said, ophthalmological genetics is in such flourishing good health. Dermatological genetics does not seem to have benefited so much from the skin being on the outside, and there are but few dermatological counterparts to the volumes of Sorsby, Waardenburg, Franceschetti and Franr; ois, among others. But thanks to the growing interest in medical genetics, and the modern sophisticated tech niques of molecular, biochemical, and ultrastructural examination, der matology is beginning to catch up, as the appearance of this volume testifies. Because of the growing body of knowledge and the heightened awareness of genetics by both patients and physicians, dermatologists not only will be asked more often about the inheritance of skin conditions they diagnose but increasingly will have the opportunity to diagnose a variety of inborn errors and syndromes by their dermatologic manifestations. On the other hand, syndromologists, clinical geneticists, and physicians are continually seeing patients with diagnostic clues in the skin that they must be able to appreciate. For both groups this book will be a new and valuable source of help. Spring 1979 F. CLARKE FRASER, Ph.D., M.D."

The impact of the retinoids in clinical practice has primarily been in dermatology. When Dr Werner Bollag began his basic research and screening programme in the early 1960's, the expectation was that the retinoids would have a major impact on oncology. However, the laboratory and clinical experiences of Bollag and his colleagues in Switzerland, Stuttgen and Orfanos in Germany, led to publications on both etretinates (Tigason) and isotretinoin (Roaccutane) in the years between 1972 and 1976 in the field of dermatology. In fact the first symposium on retinoid research held in Berlin in 1981 was almost entirely dermatological. A year later a retinoid workshop in Iowa was designed to provide a forum for dermatolog ists from the USA involved in specific protocols investigating oral retinoids. In the UK, research into the retinoids began rather later than in Continental Europe or in the USA, although Tigason was first marketed here. It was felt in late 1982 that as many dermatologists had relatively little experience with these compounds it would be appropriate to hold an International Symposium on retinoid therapy in the UK. Thus on 16-18 May 1983 in London, 37 speakers from 11 countries addressed an audience of 300, aminly UK, dermatologists. The scientific organizing committee consisted of but two persons Dr William Cunliffe of Leeds General Infirmary, representing the European Society of Dermatolo gical Research, and myself from Roche Clinical Research. The Symposium was held under the auspices of the ESDR and of Roche Products Limited."

The detection of cancer risk factors and their possible avoid ance would most effectively contribute to the fight against cancer. Research in these areas depends to a substantial degree on in vivo experimental animal models and on epide miologic studies, including data from cancer registries. When the Deutsches Krebsforschungszentrum was founded in 1964, its division "Mechanisms of Tumorigenesis" and a number of other divisions became engaged in research on chemical carcinogenesis of the skin, mainly using the mouse skin as an experimental model. Their interest orig inated in part from investigations of the new and at that time controversial pathogenic principle of conditional car cinogens as represented by certain tumor promoters which are per se noncarcinogenic. During the past 25 years, conditional carcinogens in terms of tumor promoters were established as anew, nonclassical category of cancer risk factors besides the classical solitary carcinogens. In the course of this exciting period, scientists of our center started cooperative programs with clinical dermato logists of the University of Heidelberg at the Clinics of Dermatology in Heidelberg and Mannheim, to extend the scope of their investigations into clinical oncology and to contribute by experimental approaches to solving problems in clinical oncology. This led to a gradual shift from mere animal studies to the more direct analyses of human tumors and opened up for us a new phase of research.

Each of the four authors of this book has a particular interest in disorders of porphyrin metabolism and special experience in their management. Their individual involvement in the field varies from 12 to 52 years and, combined, represents more than a century of personal experience. Since it has been written by both basic scientists and practicing physicians, the book is intended to be of value to all those involved in porphyrin metab olism and the porphyrias. It is hoped that the fascination of porphyrin metabolism and the clinical challenge of the porphyrias experienced by each of the authors will be conveyed to the readers. Michael R. Moore Kenneth E. L. McColl Claude Rimington Abraham Goldberg vii CONTENTS Color Plates ............................................ xvii 1. The History, Classification, and Incidence of the Porphyrias 1 1.1. History ........................................ 1 1.1.1. Early Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1.2. Early Descriptions of Porphyria .............. 4 1.1.3. Biochemical Developments .................. 4 1.1.4. Acute Porphyria . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1.1.5. A Complete Pathway ...................... 8 1.2. Classification of the Porphyrias . . . . . . . . . . . . . . . . . . . . . 9 1.2.1. The Current Classification. . . . . . . . . . . . . . . 12 . . . .

Several years ago a friendly looking young man walked into my office at the University Department of Dermatology in Cologne, introduced himself as a diplomate chemist, executive member of a family-owned, rather small German company manufacturing hair care products, and proposed to me straight forward to organize an international meeting on hair research. In view of the large number of new developments in the field something like this should be done after all, he said; he also promised to provide financial support. Such a meeting should be on the highest possible level, I said; and he agreed. I took the challenge and my visitor kept his promise. Three years later the First International Hair Congress was organized at the sophisticated new Congress Center in Hamburg, in which 630 participants from 36 countries were registered. After three and a half days of formal sessions, informal discussions, workshops and poster presentations our unanimous feeling was that this has been a most successful meeting. The young chemist was right. The idea was excellent. The growth and presence of hair and its distribution over the human body as a cosmetic attribute has become during the last two decades a matter of tremendous emotional significance. Hair can be rather easily formed according to one's sence of style, representing his personal image and his social feeling. If it becomes unacceptable or out of fashion, the hair style can be easily changed; the hair regrows as a biological requisite, without any additional cost.

This concise practical guide is designed to facilitate the clinical decision-making process by reviewing a number of cases and defining the various diagnostic and management decisions open to clinicians. It is richly illustrated and diverse in scope, enabling the reader to obtain relevant information regarding both standard and unusual cases in a rapid, easy to digest format. The first in the series will be on Geriatric Dermatology and will be prepared within one month of acceptance and include photos. Each case will also include a narrative description and patient management tips

It goes almost without saying that there has been a marked increase in the incidence of sexually transmitted diseases throughout the world in the past two to three decades. Indeed, despite the progress that has been made in methods of diagnosis and treatment, the sexually transmitted diseases as a whole are the most common communicable diseases and as such constitute an important health problem. The increase in incidence may be accounted for by changes in sexual behaviour, the introduction of contraceptives and the increasing mobility of the population. In addition, during the same time period, the number of infectious agents recognized as being sexually transmitted has increased considerably. These include Chlamydia trachomatis, herpes simplex virus, cytomegalovirus and hepatitis B virus. Indeed, some are as dependent on sexual transmission as the agents which cause the traditional venereal diseases and collectively they cause morbidity which has out-stripped that caused by gonorrhoea and syphilis. It could almost be said that to know the sexually transmitted diseases is to know micro biology. However, the approach taken in this book has not been to consider individual infectious agents and evaluate what they do and do not cause but to consider clinical conditions and what might be responsible for them. To cover the complete spectrum of the sexually transmitted diseases in a comprehensive way now takes a text book of massive proportion."

Urticaria is one of the most common dermatological and allergological cutaneous reactions and, compared to other diseases, it is easily recognized by patients and physicians alike. Nevertheless, the disease is highly complex regarding its eliciting causes, its clinical manifestations and its therapy. Thus, a famous New York dermatologist once mentioned that he would rather have a lion than a patient with chronic urticaria walk into his office. This may seem surprising since, to the uninitiated, different types of urticaria look alike, and the pathomechanisms are rather well understood, with mast cells being almost invariably the main effector cells. In 1986, a monograph of the first editor (Prof. Czarnetzki, now with the married name Henz) appeared, giving a detailed and thorough review of the then current state of knowledge regarding all aspects of the disease. Since then, two updates of this book have appeared in the German language, with coworkers of the clinic of Prof. Henz helping in the revision of the various chapters of the old monograph, and with particular emphasis on practical aspects of the disease. The present book is mainly a translation of the second German edition, with only minor updates and with more citations from the literature since the 1986 monograph is no longer available for purchase.

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.

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."

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.