Diabetes. Its Medical and Cultural History covers the history of scientific inquiry into this affliction from antiquity to the discovery of insulin (1921) with concurrent consideration of the history of the patient and the cultural historical background. The reprints of medical historical studies discuss general relationships as well as specific details and exceptional research achievements of the past. Included in the bibliography of primary sources are the most important historical contributions in diabetic research and diabetic therapy with the author's name and information on the place of publication. The bibliography of secondary literature consolidates international studies from the past century to the present on the history of the theory of diabetes and therapeutic approaches. Illustrations and literary texts document cultural historical relationships. In index of persons and items facilitates use of this work which is intended to provide a stimulus for the physician, medical historian, medical student, general historian as well as diabetics themselves.

The ciliopathies are a group of rare diseases that often affect multiple systems within the body, and are caused by defects in the function or structure of cilia. When cilia go wrong, there are profound consequences; these are discussed in detail for the first time in Ciliopathies: a reference for clinicians. The book provides a clinical overview and reference to this newly emergent group of disorders ranging from Alstroem syndrome to putative ciliopathic disorders. Each chapter provides an in-depth discussion on a specific disorder, including the latest scientific research together with a description of its features, and practical guidelines on diagnosis. The authors also examine the evidence for dysfunction of cilia in cancer and more common disorders. Ciliopathies: a reference for clinicians will appeal to those involved in the care of patients with ciliopathies, including specialists in the fields of nephrology, diabetes, cardiology, and ophthalmology, and non-clinical researchers interested in cilia biology.

This book will enlighten on some of the recent progress in diabetic care and therapy. Diabetes mellitus is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because of the inability of cells to respond to the insulin that is produced. According to the recent report of World Health Organization, 346 million people worldwide are suffering from diabetes, and in 2004, approximately 3.4 million people died as a result of high blood sugar. This book explores applying both classical and modern approaches to the management of diabetes by focusing on a holistic approach. Great attention has been focused on global trends in diabetes, epidemiology of diabetes, inhibitors in diabetes and diabetes therapy, vitamins and diabetes, and the role of dietary fats in diabetes in this book. Topics include: * diabetic foot ulcers and therapeutic footwear * Withania coagulans. Dunal as an antidiabetic herb * the pharmacological interventions for diabetic cardiomyopathy * the use of saliva as a noninvasive tool to monitor glycemic control in diabetic patients * a cutting-edge biomedical device for continuous in vivo glucose monitoring * the temporal effect of repeated stress in the pathophysiology of T2DM * nanosensor technology for glucose detection The editors and authors emphasize a holistic approach toward the diagnosis, treatment, and management of diabetes by joining hands with experts from various disciplines Medical students and doctors of modern medicine, Ayurveda, homeopathy, etc., medical reserachers, researchers in the area of diabetes, pharma professionals.

Thyroid function tests are utilized by essentially all medical practitioners, across every clinical setting, in patients from newborns to the elderly. They are the most frequently measured endocrine tests. The sensitive thyrotropin (TSH) assay reflects thyroid hormone feedback to the pituitary, and is diagnostic of both thyroid h- mone excess as well as deficiency. The log-linear relationship between serum TSH and thyroxine concentrations means that small changes in serum thyroxine are amplified by changes in serum TSH. The availability of the sensitive TSH assay in essentially all clinical laboratories has improved and simplified the assessment of thyroid function for the diagnosis of thyroid disease and to monitor treatment. Serum free thyroxine and thyrotropin concentrations, as well as other thyroid tests, can be measured utilizing an automated immunoassay platform that provides rapid and accurate results. This simplified approach to thyroid assessment, often requ- ing only a serum TSH measurement, and rapid availability of the thyroid function tests results, has expanded the scope of thyroid testing and clinicians ordering and interpretingth yroid tests. There remain, however, many challenges in selecting the appropriate thyroid function test to order, the correct interpretation of results, and applying these results to the diagnosis and management of thyroid diseases. It is especially important to be aware of limitations of thyroid function tests, as well as special clinical c- cumstances that can influence thyroid function measurements. The serum TSH concentration, for example, may not accurately reflect thyroid status in many si- ations including after prolonged hyperthyroidism when serum TSH remains s- pressed for months, in the presence of hypothalamic or pituitary disease, or due to a number of interfering medications. The serum free thyroxine, measured by the analog method, is not accurate with high or low serum binding proteins and d- ing pregnancy. Hospitalized patients often have thyroid function test abnormalities that are transient and return to normal after recovery from the acute illness. Iodine excessand deficiency candramatically influence thyroid function tests. Significant insights have been gained into the regulation of thyroid hormone synthesis and especially the role of thyroid hormone metabolism in supplying t- sues locally with an adequate supply of thyroid hormone. In a number of instances, these factors influence the selection and interpretation of thyroid function tests. Polymorphisms, common sequence variations, in genes of components that regulate thyroid function and thyroid hormone action may also contribute to variability in thyroid function tests in a population. v vi Preface This volume draws on an outstanding international panel of experts in thyroid function tests and thyroid function assessment. They represent clinicians, clinical researchers, and basic science researchers, all with a focus on some aspect of the assessment of thyroid function. The chapters all provide a clinical perspective, but are informed by themost recent scientific advancements. The first section of the book (Chaps. 1-3) presents the most recent advances in thyroid physiology, a review of genetic influences on thyroid function tests, and a discussion on the influence of iodine on thyroid function. In Chap. 1, Drs. Huang and de Castro Neves describe thyroid hormone metabolism, emphasizing the key role of thyroid hormone activation and inactivation in thyroid hormone action. Dr. Visser is a world leader in studies of thyroid metabolism and genetic influences on thyroid function. In Chap. 2, Dr. Visser and his colleagues, Drs. van der Deure, Medici, and Peeters, provide a clear view of this important and r- idly expanding field. The population variation in the TSH "set point" (relationship between serum TSH and thyroxine in an individual), for example, is thought to be genetically determined, and influences the evaluation of thyroid function and thyroid function targets for treatment of thyroid disease. Dr. Zimmerman, an int- nationally recognized expert in iodine, and his colleague, Dr. Andersson, provide in Chap. 3 an in-depth treatment of the most significant influence on thyroid function throughout the world-iodine intake. The influence of iodine deficiency and excess on individual thyroid function is discussed, as well as the population effects on t- roid diseases and especially fetal and neonatalde velopment. The basics of thyroid function measurements, approaches, limitations, and cl- ical applications are described for the major categories of thyroid function tests (Chaps. 4-7). The authors of these chapters are innovators in the field, strongly id- tified with the origination or significant refinement of the core tests utilized in t- roid assessment. In Chap. 4, Dr. Hershman describes the measurement of TSH, the clinical application and utilization. This remains the cornerstone of thyroid testing, but must be interpreted with an understanding of the dynamics of thyroid regulation. An active controversy in thyroid measurement involves the appropriate use of serum thyroxine measurements and especially the value of the analog free thyroxine me- urement, the most commonly used thyroxine assay. In Chap. 5, Dr. Stockigt p- vides a detailed assessment of thyroxine and triiodothyronine measurements and a clear message for their use and limitations. The most common etiology of thyroid disease is autoimmune, and the appropriate use of thyroid autoantibody measu- ments remains confusing to many clinicians. In Chap. 6, Dr. Weetman and his c- league, Dr. Ajjan, clearly describe the range of thyroid autoantibody tests and how they should be utilized clinically. Thyroglobulin measurement is the key tumor marker to follow thyroid cancer patients and Dr. Spencer and her colleague, Ivana Petrovic, describe the essential features of this measurement in Chap. 7. It is ess- tial that clinicians using thyroglobulin measurements to monitor thyroid cancer are aware of the performance of the assay being used and the factors that can interfere with the measurement. Application of thyroid function testing to the key clinical settings is discussed by expert clinicians and clinical researchers in Chaps.8-13. The appropriate selec- Preface vii tion of thyroid function tests in the diagnosis and monitoring of thyroid disease in the ambulatory setting is discussed by Drs. Farwell and Leung in Chap. 8. This is the most common setting for thyroid function test measurement and a rational approach is described. Specific issues of thyroid function in infants and children are discussed in Chap. 9 by Drs. LaFranchi and Balogh. Screening for thyroid disease among newborns has been a highly effective approach to prevent mental retar- tion. The assessment of thyroid function in newborns, especially premature infants, is challenging as are the interpretation of thyroid function tests in infancy through childhood. Illness has a significant impact on thyroid function tests and assessment in this group is described by Drs. LoPresti and Patil in Chap. 10. A logical approach to these patients is provided as are ways to identify those patients with thyroid disease that need to be treated. Assessment of thyroid function in pregnancy is ch- lenging and is being increasing recognized as a crucial time to normalize maternal thyroid status. Adverse outcome for mother and her child can result from thyroid hormone deficiency or excess. In Chap.11, Drs. Lazarus, Soldin, and Evans ca- fully describe the use and limitations of thyroid tests in pregnancy and provide an approach to testing and monitoring thyroid function. The incidence of autoimmune thyroid disease increases significantly with age and in Chap. 12 Dr. Samuels p- vides a clear approach to the assessment of thyroid status in the elderly and interp- tation of thyroid studies. The influence of drugs on thyroid function testing remains a major clinical issue with recognition of an ever increasing list of medications that influence thyroid function and thyroid testing. In Chap. 13, Drs. Pearce and An- thakrishnan comprehensively describe these medications with a special emphasis on their mechanism of action and on iodine-containing medications. I am most grateful to my colleagues for their enthusiasm and willingness to p- vide such outstanding contributions to this book. The editorial team at Springer is excellent and has been highly supportive and effective. My special thanks to E- tor Laura Walsh, Associate Editor Dianne Wuori, Editorial Assistant Stacy Lazar, Senior Production Editor Jenny Wolkowicki and Crest Premedia Solutions for final production.

A panel of outstanding investigators surveys and explains the major cutting-edge methods used in thryroid receptor (TR) research and explains their practical experimental details. Described in step-by-step detail to ensure robust experimental results, the techniques presented cover a wide variety of key areas, including TR in development and knockout (mouse and Xenopus), transcriptional regulation by TRs in both cell-free systems and in living cells, and TR mutant analysis of patients. Additional methods provide powerful tools for the isolation of TR-regulated protein complexes, for studying the oncogene v-Erba in blood cell differentiation, and for target gene analysis in the brain. Microarray chip methods are also presented for analyzing the organs of transgenic mice to identify target genes in the liver.

The central nervous system controls vital functions by ef?ciently coordinating peripheral and central cascades of signals and networks in an orchestrated manner. Historically, the brain was considered to be insulin independent. These earlier views have been challenged by ?ndings demonstrating that insulin exerts multiple actions in the brain, regulating vital biological processes such as life span, neuronal survival, cognition, reproduction, feeding behavior, energy balance, and glucose and fat metabolism, and that inef?cient central action of insulin contributes to the development of severe pathologies (Banks et al. 2000; Gerozissis 2003, 2004, 2008; Lustman and Clouse 2005; Okamoto et al. 2001; Park 2002; Perrin et al. 2004; Pocai et al. 2005; Reger et al. 2008; Schwartz and Porte, 2005; Schubert et al. 2004; van der Heide et al. 2005; Woods et al. 1979; Wrighten et al. 2008). Insulin and speci?c insulin receptors are widely distributed in the networks of the central nervous system related mainly to feeding or cognition (Baskin et al. 1983; Bruning et al. 2000; Gerozissis 2003, 2008; Havrankova et al. 1978a, b; Schechter et al. 1996; Schulingkamp et al. 2000; Schwartz et al. 1992; Zhao et al. 2004). Insulin receptors located in the synapses of neurons and in astrocytes are present in high concentrations in the cerebral cortex, olfactory bulb, hippocampus, amygdala, cerebellum and hypothalamus (Abbott et al., 1999; Havrankova et al.

The subject of this book is neuroendocrinology, that branch of biological science devoted to the interactions between the two major integrative organ systems of animals-the endocrine and nervous systems. Although this science today reflects a fusion of endocrinology and neurobiology, this synthetic ap proach is relatively recent. At the beginning of the 20th century, when the British physiologists, Bayliss and Starling, first proposed endocrinology to be an independent field of inquiry, they went to great lengths to establish the autonomy of chemical secretions in general and their independence from nervous control in particular (Bayliss, W. M. , and Starling, E. H. , 1902, The mechanism of pancreatic secretion,]. Physiol. 28:325). They argued with Pav lov, who said that there was a strong influence of the nervous system on the gastrointestinal phenomena the endocrinologists were studying. For several decades, the English physiologists prevailed, at least in the West; and Pavlov's critique was not taken to heart by the practitioners of the newly emerging discipline of endocrinology. Through the work of Harris, the Scharrers, Sawyer, Everett, and others, there has been something of a scientific detente in the latter half of this century; the hybrid field of neuroendocrinology is now regarded as one of the corner stones of modern neural science and is of fundamental importance in basic and clinical endocrinology.

Many advances have been made in the field of thermoregulation in the past few years. These include our understanding of Fever, which is now considered not simply a rise in deep body temperature foHowing infection, but just one aspect, though perhaps the most easily measured, of the Acute Phase of the Immune Response. Classification and identification of the Cytokines and the availability of recombinant material has greatly aided this research. Similarly, our understanding of the Hypothalamo-Pituitary Adrenal Axis has altered our way of thinking about temperature regulation. Of importance are the problems associated with adverse climatic conditions and survival, and the problems encountered by the neonate and the hibernator. At the biochemical level, our knowledge of the control of heat production and the role of brown adipose tissue is rapidly advancing. All these issues and many others were discussed at a Symposium 'Thermal Physiology 1993' held in Aberdeen, Scotland in August 1993 under the auspices of the Thermal Physiology Commission of the International Union of Physiological Sciences. Six main aspects of the subject of temperature regulation are included in this book, namely, Fever (including the Acute Phase of the Immune Response and Thermoregulatory Peptides), Neurophysiology of Thermoregulation, Neonatal Thermoregulation, Mechanisms of Heat Production, Ecological and Behavioural Thermoregulation, and Emerging Themes in Thermoregulation.

Fundamental to survival of living organisms is their ability to react appropri ately to their environment. Cannon (1929) recognized that "back of internal homeostatic mechanisms are powerful motivating agencies-appetites and hunger and thirst." Almost all observed behavior may be viewed as activity required to meet some physical or emotional need. "The higher in the scale of living things, the more numerous, the more perfect, and the more compli cated do these regulatory agencies become." This statement by Fredricq (1885) regarding internal mechanisms is at least as valid for behavior. Adrenal medullary secretion in preparation of "fight or flight" may be con sidered the first described behavioral neuroendocrine response. The conse quences of more prolonged stress on pituitary-adrenal cortical function and the subsequent unfolding of the means by which the brain controls the secre tion of the anterior and posterior pituitary glands led to the birth of neuroen docrinology. During the last decade, neuroendocrinology has taken a remarkable turn. Peptides which were believed at first to be involved solely in control of the pituitary by the hypothalamus were found in other areas of the brain. Other peptides were encountered in brain by their activity in competing for the high affinity binding of drugs to their receptors, and still others, first found in peripheral organs, were discovered also in brain. Perhaps even more amaz ing was the discovery that one or another of these peptides influence almost every aspect of behavior."

It is curious that research in endocrinology has largely ignored the testis until quite recently. There were two impor tant reasons for this neglect; first, methods of study were difficult, and second, sperinatogenesis was considered to be the concern of the urologist or cell biologist but not the endocrinologist. Since it is now almost an ethical imperative that we develop a male contraceptive, and since a host of new techniques can be brought to bear on problems of testis function, research in male reproductive biology has effloresced. In fact, it has become possible to project aseries of workshops on the testis, each dealing with discrete aspects of biochemistry, physiology and pathology. It is fitting that this first Workshop should be on Binding and Activation, since this area is one of the frontiers in endocrinol ogy. At our present rate of progress it is probable that each of the succeeding workshops will likewise bring together leaders in a rapidly developing area. The National Institute of Child Health and Human Development has the major Federal respon sibility in reproductive biology, and has therefore agreed to sponsor this and succeeding workshops. On behalf of the Institute and for those members of the Committee who have organized this meeting, I welcome you. I am quite sure that this first Workshop on the Testis will initiate aseries of important contributions to scientific thought in male reproduc tive biology. Mortimer B. Lipsett, M. D."

Tumours of the prostate are the commonest types of neoplasm in the male. Whilst the benign form is virtually a universal condition in the ageing male, malignant tumours rank amongst the top causes of cancer death. Despite the fact that the involvement of the testis in the growth of the prostate has been recognised for almost two centuries, it was not until the early 1940s that Charles Huggins' studies on the effect of orchidectomy and oestrogen therapy on prostatic cancer initiated endocrine manipulation in the management of this malignancy. During the 1960s progress in the understanding of the mechanism of hormone action, achieved through advances in molecular biology and the recognition of certain aspects of hormonal control in relation to the genome, introduced a new dimension for approaching endocrine manipulation of prostatic tumours. By the end of that decade a new scientific discipline devoted to prostate research had been born, which brought together investigators in the fields of molecular biology, biochemistry, endocrinology, immunology, urology and pathology to search for the cause and to explore methods for advancing the management of abnormal prostatic growth. Since then a wealth of scientific data has accumulated on the prostate in which endocrinology has manifested itself as the cardinal aspect to which most of the findings can be related.

Endocrine conditions requiring surgical intervention in the pediatric age group are uncommon. When diagnosed, they are the source of great in terest and, often, considerable debate. This is understandable, since few centers and even fewer individual surgeons can draw on vast experience of this subject. The great divergence of opinion regarding management is also understandable in that pediatric endocrine lesions often differ considerably from their adult counterparts in histology, natural history and response to treatment. Pediatric endocrine lesions are also, as a rule, less frequently malignant. In addition to the great strides made in surgical and anesthetic technique and operative monitoring, progress in four areas has substantially advanced the management of endocrine dis orders in the pediatric age group in the last decade: imaging, pathology, pharmacology and genetics. The new imaging tools, ultrasonography, computed tomography and magnetic resonance imaging, have added great diagnostic possibilities. More recent developments, such as radio nuclide imaging for the adrenal gland and the possibility of using tagged antibodies, promise to expand our imaging horizons even further. In the field of pathology, the develop ment of immunocytochemical markers (e. g. , monoclonal antibodies), the refinement in special stains and the continuous perfection of fine needle aspiration biopsies offer great new diagnostic as well as research capabil ities. Newer pharmacological agents, such as the alpha and beta blockers, the calcium channel blockers and thyroxine analogs, add a whole new level of safety to the management of the potentially lethal pheochromocytoma.

Leading researchers comprehensively translate all the latest scientific information regarding endocrine physiology and development into an understanding of the clinical pathogenesis, diagnosis, and treatment of endocrine disease. Organized by endocrine system, each section of the book concisely describes the chronological development of the human organism, from the fetal/prenatal period through childhood, adolescence, and in some cases, into adulthood. The prenatal sections review recent discoveries concerning transcription factors, homeobox genes, and human molecular mutations-the basic processes governing prenatal development of the individual endocrine organs-and detail the pathophysiology, clinical characteristics, and treatment of pediatric endocrine disorders.

This volume contains the papers presented at the Inter- national Symposium on "Cirrhosis, Hepatic Encephalopathy and Ammonium Toxicity", held in Valencia, Spain, November 27-29, 1989. Hepatic cirrhosis as well as other liver failures usual- ly lead to hepatic encephalopathy which is an important cause of death in occidental countries. However the molecular bases of the pathogenesis of hepatic encephalopathy remain unclear and several hypotheses have been proposed. Hyperammonemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy. Therefore, a part of the book is devoted to the effects of hyperammonemia on cerebral function, ammonia and amino acid metabolism, brain microtobules, astrocytes and synaptic trans- mission and their possible role in the pathogenesis of hepatic encephalopathy. Carnitine has a remarkable protective effect against acute ammonium intoxication. Thus some results regarding this effect are also presented, as well as the clinical use of car- nitine. The alterations of the metabolism of ammonia and of seda- tives in liver diseases and their clinical implications are also discussed. The possible role of altered GABA-ergic neurotransmission on the pathogenesis of hepatic encephalopathy has received considerable attention recently. Results of these studies and those on benzodiazepine receptor ligands are presented as well as those on the hypothesis of the role of altered synaptic plasma membrane on the pathogenesis of hepatic encephalopathy.

This volume is devoted to the chemistry, immunology, molecular biology, and physiology of the human chorionic gonadotropin, heG. For this glycoprotein molecule the course from discovery to chemical deciphering covered about fifty years. It was in 1928 that Ascheim and Zondek reported that urine from pregnant women contains something that stimulates the ovaries of mice or rats. This provided the basis for the famous A-Z test for pregnancy and for the "rabbit test" modification introduced by Friedman. As researchers sought to find more sensitive responses to heG, they used a wide variety of species including the South African aquatic toad, Xenopus Zaevis, the terrestrial toad of South America, Bufo arinarus, and the African weaver finch, EupZeetes afra. The weaver finch feather reaction was particularly noteworthy, for it disclosed a non-gonadal response to heG/LH. In retrospect, this may have been an important evolutionary clue to the realization that the designation of the hormone as a "gonadotropin" may have been only partially descriptive of the molecule's physiological function--a concept that is gaining attention, as the papers in this 1980 volume divulge.

Diabetes is one of the oldest diseases known to mankind. It was first mentioned in the Ebers Payrus (Egypt 1500 BC) and 'honey urine' was noted by Sushrutha in India in 400 BC. By the first century of the Christian era the disease was well known, both in Roman writings and in Chinese and Japanese writings. The word 'diabetes' was first coined by the Greeks. It means a passing-through of water. They described it as a 'melting of flesh into water', meaning urine. Then in 1674 Doctor Willis discovered by heating, tasting and evaporating urine that a sweet sticky substance was in it, which, of course, was sugar. Rut sugar was not known in England in those days and honey was the only real sweet tasting substance. The Latin word 'mel' which means honey was used and the disease came to be known as diabetes mellitus - that is, the passing of honeyed urine. This is still the full name of the disease.

Proceedings of the First International Meeting of the Pancreatic Islet Study Group held in the Alicante, Spain, November 25-28 1994

The Third Advanced Seminar in Neurosurgical Research was held in the Palazzo Pisani Moretta, Venice, Italy from 30th April to 1st May, 1987 and was devoted to "Neuroendocrinological Aspects of Neurosurgery." The general aim of these advanced seminars is to bring together European Neurosurgeons interested or involved in research work, either clinically, experimentally or both, in a given field in order to achieve in-depth informal discussions not possible in the more conventional large congress. In particular, these advanced seminars seek to provide high level teaching by experienced basic scientists, to provide "state of the art" assessment of the subject and to highlight areas of controversy that may be suitable for future research. A special effort is made to identify younger neurosurgeons through the auspices of the European Directory of Neurosurgical Research, who have a particular interest in the subject under discussion, not all of whom will have immediate access to the most advanced, modern technology. The topic of Neuroendocrinology was chosen because clinically it is an area of controversy that should be amenable to application of new techniques, including molecular biology. There is a tendency on the part of Endocrinologists not to appreciate always that disturbances seen by Neurosurgeons may be different and need special attention. Inevitably there has been a little delay in publication of the manuscripts but these have been updated appropriately.

Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It wa& decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

THE DISCOVERY OF INSULIN, C-PEPTIDE AND PROINSULlN, SPECIES DIFFERENCES Crude insulin was extracted and isolated from dog pancreases removed 7-1 Degrees weeks after ligation of the pancreatic duct for the first time in 1921 by Banting and Best. Its lifesaving properties were subsequently documented in pancreatectomized dogs in 1922. Only about six months elapsed from its discovery until systematic collection of calf and ox pancreases and, later, porcine pancreases was established and the blood glucose lowering effect in diabetics using the crude extract from these glands proven. It was not until 1960, however, that the primary structure of all three species of insulin, lO7 human, porcine and bovine, was elucidated . It then became evident that the differences between bovine, porcine and human insulin amounted to at mosl 3 amino acids. These apparently small differences have a significant impact on the physico-chemical characteristics of the three insulins which again affect, e.g., the rate of absorption of insulin lO9 preparations from the subcutaneous tissue and their immunogenicity, i.e.

A panel of expert clinical and basic investigators summarize the state-of-the-art in the use of transgenic technology in a broad range of endocrinological applications. Up-to-date and comprehensive, Transgenics in Endocrinology reviews the most recent developments in the analysis of endocrine physiology and its pathologies through mouse models, and provides a host of creative approaches to understand better the complex processes that are characteristic of hormonal systems.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

From our current knowledge, it is obvious that estrogen action in volves more than reproduction and fertility. Rather, estrogens affect and influence a number of other organ systems such as the immune, cardiovascular and central nervous system as well as the gastrointes tinal tract, urinary tract and skeleton. The importance of estrogens and estrogen receptor activity is appreciated from the spectrum of significant physiological dysfunctions that occur when there is a loss The participants of the workshop VI Preface of the hormone or the receptor activity. Loss of estrogen, however (for instance during menopause), occurs with time and results in a variety of clinical conditions. We know that the developmental loss of estrogen, as seen in clinical cases of aromatase gene mutations and experimental models, has dramatic effects in both men and women alike. The evidence that these effects are mediated through the estrogen receptor(s) is based on similar but not always identical phenotypes as observed in experimental animal models of estrogen receptor mutations as well as the single clinical case of an estrogen receptor alpha mutant patient. Developing an understanding of the spectrum of estrogen in a variety of tissues related to the condition of estrogen loss is a major and highly active clinical as well as basic scientific research area. Following the discovery of a second estrogen receptor and possible receptor ligand-independent activity as well as the genomic and non genomic actions of estrogen, it is clear that the mechanisms of the effects of estrogen are multifaceted.

Diagnostic Methods in Clinical Thyroidology provides a forum for discussion of controversial issues in three major categories: diagnosis of thyroid function, non-invasive evaluation of structural abnormalities, and needle biopsy diagnosis of thyroid nodules. For each category, a free interchange of ideas based on extensive clinical experience is followed by a summary that strives to resolve these controversial issues within a framework of sound clinical practice. The volume will this serve as a ready reference for the many physicians who evaluate thyroid patients.