This volume focuses on the investigatory methods applied to autosomal dominant polycystic kidney disease (ADPKD), one of the most common human genetic diseases. ADPKD is caused by mutations in PKD1 and TRPP2, two integral membrane proteins that function as receptor/ion channels in primary cilia of tubular epithelial cells. Thus, ADPKD belongs to ciliopathies, a group of disorders caused by abnormal cilia formation or function. This proposed book will cover the state-of-the-art methods ranging from molecular biology, biochemistry, electrophysiology, to tools in model animal studies. Key Features Explores the role of cilia in polycystic kidney disease Focuses on myriad state-of-the-art methods and techniques Reviews specific mutations integral to this autosomal genetic disease Includes discussions of model systems

His scientific contributions are regarded as classics: the studies about the insulin effect on adipose tissue (together with George F. Cahill Jr. ), his work on the biosyn- thesis and secretion of insulin (together with Lelio Orci and Claes W ollheim) and his studies on various spontaneous and induced diabetes syndromes in rodents (together with Bernard Jeanrenaud and Eleazar Shafrir). Albert Renold will be remembered for a long time by all who knew him for his achievements, for his kindness and his humanity. We dedicate the Proceedings of this symposium to his memory. Werner Creutzfeldt Pierre Lefebvre G6ttingen Liege History and Philosophy of Bayer Pharmaceutical Research W. -D. Busse Fachbereich Forschung Pharma, Bayer AG, D-5600 Wuppertal, FRG Research has a long tradition at Bayer. This year, 1988, marks 100 years of our pharmaceutical activities. In 1888 the first Bayer drug - phenacetin, an antipyreti- was synthesized, starting from a by-product of dye manufacture. This finding led to the establishment of a Pharmaceutical Department within Friedrich Bayer and Co. in Elberfeld, with all its associated facilities (Fig. 1). The beginning of the company itself, however, dates back to 1863. In that year, Friedrich Bayer started the produc- tion of aniline dyestuffs in his private house in Barmen-Rittershausen. During the 125 years of the company's life and the 100 years of pharmaceuticals, many developments and products have been discovered by Bayer researchers and launched by Bayer.

"Endocrine and Metabolic Disease" is in two sections. The first is a systematic review of clinical and therapeutic aspects of endocrine diseases, whilst the second considers the clinical pharmacology of drugs used in endocrinology. All the major areas of endocrinology and metabolism are covered. Thyroid, adrenal and pancreatic disease are discussed in depth and there are separate chapters on the ovary and testes as well as on the pituitary gland and parathyroids. There is a useful pharmacopoeia of drugs used in endocrinology at the end of the volume.

Although impotence may be the most widely recognized manifestation of male sexual dysfunction, many other forms of sexual disorders do not involve the erectile mechanism, from deficiencies of desire to disturbances in ejaculatory function to the failure of detumescence. With such a myriad-and often co-existing-number of disorders, the successful treatment of male sexual dysfunction requires not only a thorough understanding of the underlying physiology and pathophysiology, but also the coordinated efforts of multiple specialties, including endocrinology, andrology, urology, radiology, sex therapy, and even sometimes psychiatry, cardiology, or oncology. Male Sexual Dysfunction: Pathophysiology and Treatment presents the collective expertise of more than 60 international authorities in a single landmark text. From foundations in the anatomy of the male genital tract to the latest neuroimaging data, readers will appreciate the comprehensive information detailing the tremendous advances made in the delineation of sexual function and its disorders as well as the expert descriptions of practical and cost-effective medical, surgical, and psychological strategies for the treatment of all forms of male sexual dysfunction.

Das Spektrum der in den westlichen Industrienationen filhren- den Krankheiten und der darauf basierenden Thdesursachen hat sich in den letzten J ahrzehnten gewandelt. Wahrend frliher die Infektionskrankheiten und speziell die Thberkulose den hochsten Todeszoll forderten, sind in den Jahrzehnten nach dem zweiten Weltkrieg mit steigendem Wohlstand die Herz- und GefaBkrankheiten an die erste Stelle gerlickt. Trotz gewis- ser Erfolge in der Pravention in einigen Uindern wie z. B. in den USA, Kanada, Australien; aber auch in einigen Gebieten West- europas, in denen die Zahl der tOdlichen Hirnschlage und Herzinfarkte inzwischen wieder rlicklaufig ist, wird die Spit- zenposition in der Todesursachenstatistik hier auch weiterhin von diesen Krankheiten eingenommen. In anderen Uindern wie z. B. in Osteuropanehmen die Erkrankungsraten weiter zu. Wenn man sich fragt, was getan werden kann, urn weitere Er- fqlge auf diesem Gebiet zu erzielen, dann ist ein Blick in die Lander des Fernen Ostens hilfreich. In der Volksrepublik Chi- na undin J apanliegt die Sterblichkeit an koronarer Herzkrank- heit bzw. an Herzinfarkten flinf- bis zehnmal niedriger als in der Bundesrepublik Deutschland. Arteriosklerotische Durch- blutungsstorungen der unteren Extremitaten, auch diabeti- sche GefaBerkrankungen kommen dort kaum vor. Vergleicht man die Lebensweise der Bevolkerung in diesen Uindern mit den Verhaltnissen in den westlichen Industriena- tionen, so fallenerhebliche Unterschiedeinder Ernahrungauf. Wahrend in China Fleisch und Molkereiprodukte in deutlich geringeren Mengen als bei uns verzehrt werden, besteht der Hauptanteil der Ernahrung aus einer an pflanzlichem EiweiB und Schlackenstoffen reichen Kost.

In September of 2007 Gaucher Disease received a commendation in the Haematology category of the 2007 British Medical Association Medical Book Competition! Although rare in the general population, Gaucher disease is the most prevalent of the lysosomal storage disorders, making research into this particular orphan disorder an invaluable prototype for the diagnosis, research, and treatment of others. Like many rare conditions, Gaucher disease has benefited from the explosion of medical research in the last decade, the amount of new information on this disease is staggering and the rate of new discoveries has left previous books on the subject unable to provide useful, up-to-date information. The most current, fully comprehensive reference to date, Gaucher Disease provides valuable information for academic and industry scientists, and clinicians. Outlining the latest research on the biochemical mechanisms and pathology of lysosomal storage disorders, this book covers diverse topics including animal models, crystallography, imaging and radionuclide evaluation. It not only addresses the developmental basis for current treatments like the now widely available enzyme replacement therapy, but also includes chapters introducing new therapies on the horizon. With contributions from world-renowned experts in substrate reduction therapy, pharmaceutical chaperone therapy, hematopoietic stem cell transplantation and gene therapy, as well as chapters on a second generation of enzyme replacement therapy, this book explores the full spectrum of possibilities offered by the most recent advances in medicine. Some of the most interesting aspects of the book include the discussions on patient management, those touching on the ethics of research, and the societal aspects of treating rare diseases with expensive therapy.

In recent years, the clinical evolution of thyroid diseases has been studied exhaustively as new discoveries have been made about thyroid malfunction and the effective management of patients. Thyroid Diseases presents a comprehensive exposition of a range of disorders caused by thyroid dysfunction. With contributions by well-known experts in the field, the book is the first compendium in several decades to assemble a vast amount of data and research into one volume. Following a methodological format, each chapter explores a different malady or condition. After defining the dysfunction or disease, the text presents the epidemiology, etiopathogenesis, clinical features, first and second level tests for diagnosis, first and second line therapies, prognosis, and recommendations for follow-up. Highlighted topics include: Transient forms of hyper- and hypothyroidism Subclinical hyper- and hypothyroidism Thyroid dysfunction during gestation and postpartum The influence of iodine on the thyroid during pregnancy The importance of drugs that modify thyroid function Thyroid disrupters that affect thyroid homeostasis The bimodal and/or transient development of some thyroid diseases The evolution of diagnosis, priorities of therapies, and lifelong monitoring of patients All of the contributors to this text pursued long periods of training in elite research laboratories. They are active investigators and well known in the international arena. The information presented in this volume is invaluable for practicing clinicians and those training in internal medicine, endocrinology, surgery, and other areas of medicine.

The authors have provided an overview of the relationships between hormones that are physiologic constituents of the body as well as their pharmacologic use in replacement therapies and related endocrine dys function. Principles of Endocrine Pharmacology concerns itself with the ther apeutic use of hormones, and hormone like substances, or drugs that can act either by suppressing or enhancing the metabolism of certain glands of internal secretion. Other drugs used for nonendocrine ther apies can likewise affect the endocrine system. Endocrine pharmacology emerged in the early 1900s with the use of crude pituitary extracts. By the mid-1900s several investigators had isolated and begun to synthesize hormones or hormonelike substances. Recognizing the limited supply of hormones that could be obtained both from animal sources and human autopsy material, the search for so called hormone substitutes also began early in the 1900s. Recently, re combinant DNA technologies have been used to provide alternative therapeutic sources of human insulin and human growth hormone. Aside from insulin, perhaps no other use of hormonally-active sub stance is better exemplified by those drugs which affect fertility. The synthesis of an orally-effective steroid represented one of the first major breakthroughs in the chemical suppression of ovulation. Since the orally active 19-norsteroids were introduced in the 1950s, several oral contra ceptive steroid preparations have been marketed. Indeed, the advent of oral contraceptives for birth control has led to a renewed interest in endocrine pharmacology."

Clearly presented and thoroughly up to date, this important text provides an overview of current knowledge of the polycystic ovary syndrome (PCOS) - its etiology, pathology, and the implications for effective medical management. In contrast with existing titles, this book focuses on the difficulty in making an accurate diagnosis and the consequential problem of identifying the most effective program of management. Key features: * coherent approach, integrating international contributions * first book on PCOS since the Rotterdam Consensus meeting * focuses on clinical manifestations of disease, diagnostic criteria and options for management * illustrated with tables, graphs and charts to explain physiologic principles. Among the most important consequences of PCOS is infertility, and the authors provide clear guidance on the role of new assisted reproductive technologies to overcome this problem.

This book contains the necessary knowledge and tools to incorporate nutrition into primary care practice. As a practical matter, this effort is led by a dedicated primary care physician with the help of motivated registered dietitians, nurses, psychologists, physical therapists, and office staff whether within a known practice or by referral to the community. It is essential that the nutrition prescription provided by the physician be as efficient as possible. While many team members have superior knowledge in the areas of nutrition, exercise, and psychology, the health practitioner remains the focus of patient confidence in a therapy plan. Therefore, the endorsement of the plan rather than the implementation of the plan is the most important task of the physician. This book proposes a significant change in attitude of primary health care providers in terms of the power of nutrition in prevention and treatment of common disease. It features detailed and referenced information on the role of nutrition in the most common conditions encountered in primary care practice. In the past, treatment focused primarily on drugs and surgery for the treatment of disease with nutrition as an afterthought. Advanced technologies and drugs are effective for the treatment of acute disease, but many of the most common diseases such as heart disease, diabetes, and cancer are not preventable with drugs and surgery. While there is mention of prevention of heart disease, this largely relates to the use of statins with some modest discussion of a healthy diet. Similarly, prevention of type 2 diabetes is the early introduction of metformin or intensive insulin therapy.

In 1920, Hirose demonstrated the luteinising effect of placental tissue and one year later, Evans and Long described luteinised ovaries in rats treated with hypophysial extracts. In 1926, Zondek and Aschheim as well as Smith, independently of each other, showed that a gonad-stimulating hormone was secreted by the adenohypophysis. In 1927, Aschheim and Zondek found their "Prolan" in human pregnancy urine and the first reliable pregnancy test was available. In the following years it could be demonstrated that the gonadotropic hormones from pituitary and from pregnancy urin were not of identical structure. During the years 1931 - 1933 Fevold and coworkers prepared follicle stimulating hormone from sheep pituitaries which were free of other hormone activities. Already in 1934, Collip found "antihormones" in animals treated with proteinhormones from animals of another species. It could be shown that they were antibodies against these hormones and this was the future basis for the immunological era starting in 1960. The quantitative determination of gonadotropins has been performed over several decades by difficult bioassays and since 1960 immunological and later radioimmunological assays became available. Since that time a new field was opened for the studies of gonadotropins. During this time, highly purified preparations of gonadotropins were available for research and clinical treatment. I recall the first successful attempt of inducing follicle growth and ovulation by Gemzell and coworkers 1958 as well as by Lunenfeld and Bettendorf at about the same time.

Der innersekretorische EinfluB auf Stimmung, Befindlichkeit und Leistungsfahigkeit des Menschen ist ein faszinierendes Aufga- benfeld der forschenden und praktizierenden Medizin; er ist auch fOr die betroffenen Menschen von groBtem Interesse und groBer Bedeutung. Mit den damit zusammenhangenden Fragen befassen sich besonders die Arbeitsmedizin und in den letzten Jahren zuneh- mend auch die Sportmedizin. Dieses Engagement ergibt sich einmal aus der Bedeutung der Leistungsfahigkeit fOr diese Berei- che, zum anderen methodisch aus der Moglichkeit, innersekreto- rischen Parametern exakte Werte der Arbeit und des Leistens gegen 0 berzustellen. Gerade beim weltweiten Phanomen stark ansteigender Zahlen im Frauensport und der gleichzeitigen rasanten Entwicklung der Spitzenleistungen treten verstarkt Probleme innersekretorischer Regulationen aus frauenheilkundlicher Sicht in Erscheinung. Vielerorts wird von Arzten, Trainern und Sportlern mit Hormon- wirkungen argumentiert, ohne daB solchen Aussagen immer auch gesicherte Fakten zugrundeliegen. Der Deutsche Leichtathletikverband, darOber hinaus aber der Sport schlechthin haben allen AnlaB, der Universitatsfrauenklinik in TObingen fOr ihr Engagement auf diesem Sektor zu danken. Die im Rahmen dieses Symposiums ausgetauschten Kenntnisse, Erfahrungen und Anregungen werden dazu beitragen, die in Frage stehenden Zusammenhange aufzuklaren. Das aber wirQ nicht nur fOr den Sport von Nutzen sein, sondern Vorteile fOr Diagnostik und Therapie in Klinik-, Fach- und Aligemeinpraxis bringen konnen.

Klinefelter's syndrome occurs relatively frequently, being diagnosed for one in 600 male infants, yet it is probably very rare that it is recognized early enough to make effective treatment possible. Often the person afflicted does not go to a doctor until physical and emotional disturbances have developed on the ba sis of the syndrome. The appropriate therapy at the correct time can prevent many of these disturbances. In our andrology outpatient clinic we encountered Klinefelter's syndrome almost three decades ago in patients suffering from impotentia generandi. It was not until later that we dealt with it in our capacities as dematologists. It was observed at a rate too high to be coincidental among younger men suffer ing from ulcera crurum. On the other hand, we failed to see the condition during our work as con sultants in other specialities, especially internal medicine, although we re peatedly attempted to identify it. We should have encountered it at least occa sionally in our 10 years working in the Munich hospitals with their more than 4000 beds. It was this imbalance between the allegedly relative frequency of this condition and its rare detection which led us to plan a Klinefelter sympo sium. We soon determined, during a first search of the literature, that there was information in many more subject areas that we had expected or even guessed."

Table 19. Local structural effects of endocrine diseases Endocrine symptoms and signs are rarely specific. This fact renders the art of recognizing an endocrine Structure affected Feature disorder in a patient more often one of suspecting rather than 'diagnosing' it. Unlike most other body Hypothalamus Headaches Pituitary Headaches, visual defect 'systems' the very nature of the endocrine system Thyroid Pressure symptoms, dysphagia, ensures that the effects of disordered function in a goitre gland affect the body as a whole and cause diffuse Gonads Testicular lumps, ovarian masses symptoms and signs. Most patients with a cardiac problem present with one or more specific symptoms such as chest pain, palpitations and oedema. The problem then becomes one of resolving whether a cardiac problem exists or not and, if so, what is the nature of the disease process. HISTORY Similarly, most patients with a gastro-enterological and neurological problem will present with a specific Present history symptom - diarrhoea, or tremor - which will direct attention to that organ system.

During the past 3 years, little has been added to our funda mental knowledge of hormonal disorders in gynecology. Diagnostically, however, there has been an almost com plete departure from traditional chemical methods in favor of radioimmunoassay techniques. As a result, diagnostic capabilities which previously were restricted to large cen ters have now been extended to the office and small clinic. Accordingly, the chapters dealing with these techniques have been revised and updated. There is also new material on advances in the hormonal treatment of endometriosis and hyperprolactinemic states. Finally, the bibliography has been extensively revised to include a number of recently published books and survey articles of general interest. Paul J. Keller v Preface to the First German Edition Menstrual disorders and sterility are among the most com mon complaints noted by both the specialist and general practitioner. For many patients they are far more distress ful than is generally assumed. Recent years have brought our knowledge. While this has led to great advances in major improvements in the results of treatment, it has made it difficult for the nonspecialist to keep abreast of developments in the field of gynecologic endocrinology.

The development of accurate hormonal assays in recent years has evoked much interest in the area of anaesthesia and surgery. In an effort to allow an exchange of ideas and new information in this area, the First International Symposium on Endocrinology in Anaesthesia and Surgery was held in Bonn during September 1978. The contents of this book represent much of the information presented by the leading authorities in this field. The presentations were grouped in three areas: 1. Basic problems of endocrinology in anaesthesia and surgery; 2. The response of the endocrine system to anaesthesia and surgery; 3. Hormone and anaesthetic management of endocrine disease. As with any multi-authored text, there is both repetition and diversity but hopefully the reader will be able to obtain much of the useful information. As Editors, we wish to express our deep appreciation to Profes sor R. Frey and Springer-Verlag for including this book in the series on "Anaesthesiology and Intensive Care Medicine." H. Stoeckel T. Oyama Table of Contents I. Basic Problems of Endocrinology in Anaesthesia and Surgery H. Breuer Basic Principles Regulating the Endocrine System . . . . . . . .. 3 G. Wesemann and E. Grote Pathophysiology of Intra- and Postoperative Stress .. . . . . .. 10 M. Trede Surgical Treatment of Endocrine Disorders .. . . . . . . . . . .. 24 T. Oyama Influence of Anaesthesia on the Endocrine System ... . . . .. 39 L. Nocke-Finck Radioimmunological Determination of Hormones."

We live in an era of "explosions." Not the least threatening of these inflationary events is the information explosion. In spite of data banks, automated indexes, and computerized retrieval systems, science is being overflooded by its products. Much of the responsibility for this state of affairs must rest with a system that tends to reward quantity rather than quality of publications, and on the resulting misap prehension that the aim of scientific research is the gathering of data rather than the advancement of knowledge. The sponsors of congresses and symposia who insist on a lasting record of their proceedings, the authors and editors who have no compunc tion about printing trivial or redundant information, and the publishing houses them selves, which can hardly be expected to favor restraint, also bear part of the respon sibility. One of the consequences of the information explosion is a change in our attitude towards new books. Whereas we used to welcome their appearance and to take them as useful and good until proven otherwise, we now greet them with suspicion and wonder even before opening them whether they were really necessary. Fortunately, some of them still are and perform a real service by taking an unwieldy mass of data dispersed in a variety of journals, and organizing it into a coherent synthesis of the state of knowledge in a given field. Such books actually serve to advance knowledge and become landmarks."

Either deficient or excessive hormone production has been observed with respect to some rather bizarre clinical manifestations. Starting with the synthesis or isolation of pure hormones in the early 30s, estrogens (the female sex hormones) and androgens (the male sex hormones) have become readily available for clinical and other uses and their physiologic activity has been intensively studied. The relationship between hormones and cancer was perhaps one of the earliest research areas in cancer. In the early work of the 20s it was clearly shown in experimental animals that under certain conditions both endogenous and exogenous hormones could induce certain cancers and tumors. More recently, attention has been focused on the use of androgenic anabolic steroids by athletes as body builders and the widescale multiple use of estrogens in terms of carcinogenic hazard. Most striking in recent years are the potential adverse effects of estrogens relevant to sterility, gall bladder disease, and neoplasia. The pervasive environmental hazard contributed by estrogens may arise from variant sources. Such sources may be: (a) endogenous hormones, (b) estrogenic compounds occurring naturally in foods or as fungal con taminants in food stuffs, ( c) estrogens added to livestock feed, (d) estrogenic additives to cosmetics, (e) oral contraceptives, and (f) estrogens used clinically for threatened abortions, lactation suppres sion, menstrual anomalies, and therapeutic treatment of certain forms of cancer."

F. Kruck It is a great pleasure for me to welcome you to the workshop on Natriuretic Hormone here in Bonn. For quite a long time we have been considering the possibility of assem bling scientists who are concerned with and interested in the problem of a possible humoral natriuretic activity. Work has been done on this topic in different parts of the world, partially with different methods and sometimes also with different and contlict ing results. And thus we thought it could be very beneficial to have personal discussions with all of you so as to reach a consensus of opinion on how studies should be contin ued. In spite of the current fmancial shortCOmings, common to most of the countries you are living in, we felt it necessary to use all the money we were granted for our research work in clinicopharmacologic studies to organize this meeting. And so we did. Thanks to the help of different pharmaceutical companies we were able to defer the travel ex penses and costs for hotel accomodation for the speakers. Thus this meeting is not going to be a luxurious one, but rather a meeting for working and especially for discussions. And now by way of opening this workshop, lowe you a few explanations."

Symposium on Lipoprotein Metabolism, held in Heidelberg, September 10-13, 1975