Dr. BRUNO BLOCH, professor of the Dermatological clinic of Zurich, began a new era of eczema research by attempting to sensitize guinea pigs to primula. It was during this period that I had the pleasure of being Dr. BLOCH's chief resident, and could observe these experiments. It was only in 1955 that Dr. E. BUJARD, professor of Histology of the University of Geneva, Dr. R. BRUN, chief of laboratories of my Dermatology Department and I began to work in the field of experimental eczema on the nipples and flanks of guinea pigs. Besides these collaborators, to whom I am very grateful, a few others have participated in our experiments. Among these new co-workers the most im portant was Mrs. NICOLE HUNZIKER, chief resident of my clinic. From 1960 on, she worked on the eczema experiments with guinea pigs. Our research has been conside rably advanced by Dr. HUNZIKER. Untill now we have published 30 communica tions on this subject, but the publications about our results have been very short. It now seemed appropriate to publish a monograph and Dr. HUNZIKER undertook this very toilsome task. I would like to take this occasion to thank her for her many years of collaboration both in the clinic and in the laboratory. I am also very grateful to Professor BUJARD who, in spite of the fact that he is retired, continues to work with us. We continually profit from his great experience. Dr.

Taking advantage of the accessibility of the skin "in vivo," non-invasive methods were developed about 40 years ago, which have now developed as accurate sources to measure skin properties and structures at the microscopic and macroscopic levels. However, even at the dawn of the twenty-first century, the mechanisms involved in these properties are still only partly understood. As in many domains, including biomedical engineering, numerical modeling has appeared as a complementary key actor for improving our knowledge on skin physiology.

This book gathers, for the first time, chapters describing scientific computing and numerical modeling for a deeper understanding of mechanisms involved in skin physiology. The book is structured around some skin properties and functions, including optical and biomechanical properties, skin barrier function, and homeostasis, covered through several chapters describing either biological or physical models at different scales.

It is now thirty years since William Montagna and Richard Ellis edited 'The Biology of Hair Growth". In his introduction, Stephen Rothman, of the University of Chicago, USA and one of the driving forces behind research on skin at the time, wrote: 'The pilary system is a perfect micr9cosmic structure. In this microcos- mos we find birth, development, ageing and death, activity and rest, color for- mation and decolorification, greasiness and dryness, infection and sterilization, hypertrophy and atrophy, Qenign tumours and malignant ones. " He foresaw the human pilary system as a model for the study of a multitude of human diseases including ageing and cancer. It was not, how- ever, until the seventies that the development of micro-biochemical tech- niques indeed allowed the use of the human hair follicle as a convenient biopsy tissue for Biomedical Research in general. Measurement of enzyme activities, and important co-factors, and culturing of cells from single follicles all became possible. In the eighties dermal papilla cells were grown in cul- ture and this opened the way to study hair differentiation in vitro. Studying hair differentiation is, in fact, studying growth regulation and it is this aspect that by far transcends the importance of studying hair growth itself. Let us not forget that metastatic prostate cancer is treated with the same drug -cyproterone acetate -that is used for the treatment of alopecia and hirsutism in women.

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.

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 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."

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 recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued un resolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

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.

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.

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 . . . .

Both the major and minor salivary glands can be the site of a wide variety of diseases and functional disturbances. This monograph covers both the common lesions and conditions of the salivary glands as well as the rare ones. Much attention is given to the problematic complaint of dry mouth and the even more cumbersome diagnostic aspects of Sjogren's syndrome. Emphasis is on the clinical aspects and the management of the various disorders. The vast experience of the authors is reflected in their clear and concise style. The illustrations are well chosen and updated references are provided, where appropriate."

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.

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."

Numerous diseases in the areas of orthopaedics, rheumatology, and radiology can only be completely diagnosed if the corresponding conditions of the skin and mucous membranes are included in the diagnostic work-up (skin-bone). Conversely, dermatologic assessment of skin symptoms in isolation may lead to serious delays and errors in the diagnosis and treatment of associated changes in the musculoskeletal system. This monograph gives an interdisciplinary synopsis, from a dermatologic and clinical radiologic perspective, of 85 disease entities which in practice are likley to present. For orientation purposes the main dermatologic and radiologic symptoms are presented in table form at the beginning of the book.

Evaluation and Treatment of the Aging Face is the definitive source for physicians wishing to master the latest advances in facial refinement. Solely addressing the aging face, the authors - all international authorities in dermatologic surgery - have compiled instructional, practical information on basic technique, anesthetics, causes, and treatment for a wide variety of procedures, including: - factors involved in the initial patient evaluation - sunscreens and retinoids - the use of glycolic acid - chemical peels and dermabrasion - liposuction and lipotransfer - rhytidectomy and blepharoplasty - diagnosis and treatment of skin lesions of the aging face - hair replacement - treatment of aging hands - how to develop an office based cosmetic surgery center.

Over the past ten years, carbon dioxide laser surgery has made impressive strides and is now applied to every field of surgery without exception. It is the intention of this book to record the work done in this field in the Department of Plastic and Maxillofacial Surgery of the Beilinson Medical Center and Tel Aviv University Medical School, Israel, as well as that performed in association with other depart ments. In this context, one feels that it is incumbent upon one to acknowledge the cooperation of the medical and paramedical staff of the Department of Plastic and Maxillofacial Surgery of the Beilinson Medical Center, as well as that of Prof. Yehuda Shindel and Dr. Daniel Katenelson of the Department of Ear, Nose and Throat, Dr. Y ona Tadir of the Department of Obstetrics and Gynecology and Dr. Itamar Kott of the Department of General Surgery. I should like to make special mention of Dr. Ralph Ger of New York, who worked with me on the original clinical trials, and the engineer Uzi Sharon, who developed the Sharplan Laser with me. The progress of Laser Surgery is well demonstrated by the participation in the four meetings of the International Society for Laser Surgery, the first of which was held in Tel Aviv in 1975 with an attendance of 65 and the last in Tokyo in 1981 with an attendance of 1200.

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.

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."

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."

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."

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.