The secretion of bioactive products by tumors of the gastroenteropancreatic system results in the development of watery diarrhea that can lead to death in a very short period if not brought under control. Even if the consequences are less dramatic, the patients' ability to lead a normal daily life is seriously impaired, and they may become severely depressed. SandostatinR alleviates the condition by inhibiting peptide release, and its long duration of action makes it an effective and rational adjunct to therapy at all stages. Last year a consensus Round Table Meeting was held in Scottsdale, Arizona, to discuss the optimal use of SandostatinR in this indication. These guidelines offer the results of clinical research and the dosage recommendations arising from them, together with a critical summary of the points of view presented.

Conceptual advances in the biological sciences are marked by the applica tion of new techniques and experimental strategies. Nowhere has this ge neric principle been more apparent than in the study of testicular cells, as judged by the evolution of themes presented at the Testis Workshop over the past 23 years. Like its predecessors, the 1995 Testis Workshop was structured to offer fresh insights and approaches for understanding the mechanisms of spermatogenesis and steroidogenesis. The chapters pre sented in this book emphasize three aspects of testicular cell function: first, the molecular analysis of the cell cycle; second, examination of the cell cycle, including the function and identification of specific macromolecules that direct the proliferation and differentiation of germ cells; and third, the development of Leydig cells and the role of specific macromolecules in the formation of testicular steroids. Each chapter is based on a lecture presented at the XIIIth Testis Work shop held on March 30 to April 1, 1995, at the Radisson Plaza Hotel in Raleigh, North Carolina. The selection of topics reflects the recommenda tions of the workshop'S organizing committee. Sincere thanks are due to the speakers who agreed to lecture and prepare chapters."

The XIIth North American Testis Workshop was held in Tampa, Florida, April 13 to 16, 1993. The program consisted of 23 invited lectures and 120 poster presentations. In keeping with the tradition of the Testis Workshop, every attempt was made to emphasize recent develop- ments in the study of endocrine and gametogenic functions of the male gonad. Although the main emphasis, reflected in the title of the pro- ceedings, was on the function and control of somatic cells in the testis, one session was devoted to germ cells and one to the studies of male reproductive development and function. The last session of the workshop was included in the program of the Postgraduate Course of the American Society of Andrology, which held its annual meeting in Tampa imme- diately following the workshop. This volume consists of 21 chapters prepared by the speakers and 8 chapters contributed by presenters of the posters. The Program Committee consisted of Drs. Nancy Alexander, C. Wayne Bardin, Andrzej Bartke (Chairman), Kevin J. Catt, Claude Desjardins, Maria Dufau, Michael Griswold, Norman Hecht, Aaron Hsueh, Dolores J. Patanelli, Bernard Robaire, and Richard Sherins. The workshop was generously funded by Serono Symposia, USA, which also agreed to handle registration, local arrangements, and publication of this volume. On behalf of the Program Committee and all participants, I would like to thank Dr. Bruce Burnett of Serono Symposia, USA and his staff for their efforts and support in every aspect of the organization of the workshop.

"Man's natural instinct, in fact, is never toward what is sound and true. It is toward what is specious and false . . . The ideas that conquer the race most rapidly and arouse the wildest enthusiasm and are held most tenaciously are precisely the ideas that are most insane. This has been true since the first 'advanced' gorilla put on underwear, cultivated a frown and began his first lecture tour, . . . " H. L. Mencken, from Meditation On Meditation in the Smart Set, June, 1920 pp 45-46 In our opinion there is no field of clinical medicine in such a state of dynamic disequilibrium as clin ical thyroidology. Thyroid diseases are very common. The moderately complex but easily understandable physiological interrelationships between the thyroid, pituitary and hypothalamus have provided stimuli for the application of mod ern technology in the development of an array of diagnostic procedures. Although therapeutic methods have been more stable, and recent advances more limited, their application by phy- Joel I. Hambufl er. M. D. sicians representing different disciplines has pro vided an ample basis for the expression of differ ing viewpoints. Unfortunately there are few opportunities for in-depth exploration of different attitudes and experience relevant to issues of current interest. The review process employed by medical journals often seems to stifle the expression of controver sial viewpoints."

The first Meadowbrook Symposium was held in 1978 and during the intervening ten years our knowledge concerning how steroid hormones function at the level of gene expression has advanced by leaps and bounds. In this volume, which sum marizes our fourth meeting, these advances are very evident. What seemed like science fiction ten years ago has become commonplace science. Who would have imagined that we could synthesize a nucleotide sequence that binds a specific steroid receptor and acts as a controlling element for gene expression? No one; but as is evident from the results reported in several chapters, this technique is yielding a wealth of information. Using these and other techniques it has become apparent that gene transcription is controlled by interactions between transacting factors and DNA recognition sequences (response elements). These transacting factors appear to be members of a large gene family that includes steroid hormone receptors, transcription factors, protooncogenes and homeobox proteins. Thus a great deal has been learned, but as usual, questions remain. Many of these questions are posed by the findings and observations found in several chapters in this volume. Non hormone binding forms of steroid receptors and their relevance to receptor down regulation, recycling and biological response remain a mystery. The quantitative relationship between receptor binding and biological response still presents agonizing problems. These and many other intriguing questions are discussed in this volume and set the stage for what should be a most rewarding time in endocrinology. Winter 1989 ARUN K."

Polycystic ovarian disease, or polyfollicular ovarian disease, as Dr. Fut terweit prefers to call it, is a disease of uncertain etiology and for which numerous modes of therapy have been advanced. Understanding of its pathophysiology should shed light on factors regulating normal ovarian function; the converse is also true. Recent years have brought about great understanding of the neuro endocrine regulation of gonadal function, as well as of factors in the microenvironment of the ovary which affect its function. It is also ap preciated that cases classified as polycystic ovarian disease actually rep resent a clinical and pathological spectrum which may reflect the effects of diverse etiological factors. In the present volume, Dr. Futterweit presents the fruits of his long interest in and extensive experience with this disease. He thoroughly and thoughtfully reviews the vast amount of basic and clinical information that has been garnered with regard to this condition over the past decade. The numerous theories that have been advanced to explain its etiology are presented in balanced fashion, in addition to a hypothesis, which is well formulated and amenable to clinical testing. His clinical interests and judgment are well represented by his presentation of the diverse manifestations of this condition, the approach to proper diagnosis, and the available therapeutic options. Patients with this disease represent diagnostic and therapeutic prob lems in a situation where manifestations of disease may lead to major emotional stress."

Tamoxifen has persisted as a widely accepted and administered drug for almost 25 years. Following the many scientific papers and books on the subject, it has remained a very intriguing substance. This, perhaps, is the reason for another monograph on Tamoxifen. It is regrettably true that overviews, even when up to date after exhaustive research - the shibboleth of our cultures -, rapidly lose relevance with the passage of time. Scientists can sometimes be pictured as deep sea divers, who plunge into the unknown in search of a hitherto unknown world. Their descent is exciting, but eventually they must come up for air and integrate their experiences with others who also had to resurface. This book intends to collect and, where possible, to collate recent, but sometimes seemingly unrelated information. To quote Stephane Mallarme: "Everything in the world exists to end up in a book." Even if this is a tad cynical, it might not be far from the truth. If a little knowledge is a dangerous commodity, one can also add - tongue in cheek - that a vast amount of knowledge can be truly hazardous. It is likely that what might seem as entangled data is confusing, especially for those satisfied with the comfortable interpretation of Tamoxifen as an antiestrogen which has long been found insufficient. The complexity of its mechanisms and effects defies simple explanations and may even seem capricious, but only because of our ignorance.

For many years now, our understanding of the somatotrophic and reproduc tive axes has evolved essentially independently, both fields of study reaching a highly advanced, although far from complete, level of under standing. Along the way, however, it became apparent that in some circumstances the reproductive and somatotrophic axes may be inter dependent. Inklings to this effect were at times feeble and at other times more convincing. Among those inklings are the clinical recognition by pediatric endocrinologists of the apparent association between isolated GH deficiency and delayed puberty, as well as of the apparent permissive, pUberty-promoting property of GH. Equally important is a body of experi mental studies establishing the ovary of multiple species as a site of GH reception and action. Arguing against an essential role for GH in the reproductive process is the observation that individuals who have GH resistance of the Laron variety are fertile arid that isolated GH deficiency does not constitute an absolute barrier to the attainment of sexual maturation and fertility. The intraovarian insulin-like growth factor (IGF) hypothesis proposes that IGFs may serve as amplifiers of gonadotropin action. Although the dependence of intraovarian IGFs on systemic GH action has never been unequivocally demonstrated, that leap of faith has often been made. The intraovarian IGF hypothesis serves as the rationale for the adjunctive use of GH in the induction of ovulation."

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.

The importance of osteoporosis in the United Kingdom as a cause of death and disability is now well recognised. There are in excess of 200,000 osteoporotic-related fractures in the UK per annum asso ciated with an estimated cost of GBP942,000,000. Following hip fracture it is known that about 50% of patients are unable to live indepen dently and about 20% of such patients die within the first 6 months. These figures, compelling as they are, reflect poorly on current medical practices which manifestly have failed to identify patients with low bone density at risk of fracture. The hope is that the techni cal advances which have enabled bone mineral density, and other allied indices, to be measured with high precision and accuracy offers the chance of identifying patients at risk of fracture and guiding the clinician to make treatment decisions which may reduce the patients' risk of fracture. In the UK, services for identifying patients at risk of fracture are still in their infancy and are not uniformly available throughout the country. This situation is, however, likely to improve particularly fol lowing the publication of the Royal College of Physicians report "Osteoporosis -clinical guidelines for prevention and treatment" and the recognition in "Our Healthier Nation" that osteoporosis pre vention should be included as a target to achieve a reduction of 20% in accidents by 2010.

Three years ago, most authors contributing to this book gathered at the Heinrich Fabri Institute of the University of Tubingen at Blaubeuren near Ulm in Germany for the third conference on "Pineal Gland and Cancer." In 1987, the late Derek Gupta organized the second meeting and published the first book on the topic, 10 years after Vera Lapin, as part of the 25th anniversary celebrations of the Vienna Cancer Research Institute, had held the first meeting. It was in Vienna during the 1930s and 1940s that W. Bergmann and P. Engel demonstrated that pineal extracts possess growth inhibitory properties on experimental rodent tumors and R. Hofstatter reported favorable results when these extracts were given to cancer patients. In the 1970s, Vera Lapin and others reported that surgical removal of the pineal gland (pinealectomy) stimulates experimental tumor growth rendering fundamental support for an involvement of the pineal gland in malignancy. A focal question of past and present research in this field is whether the pineal gland exerts its tumor inhibitory activity primarily or exclusively via melatonin. Currently, it appears that the action of melatonin on experimental tumor growth criti cally depends on the circadian timing of its administration as weH as on the type and stage of cancer, and that primarily highly differentiated tumor ceHs are controHed. Initial clinical applications of the pineal hormone for incurable cancers raise hopes for a promising future use, particularly when combined with other therapies (e. g."

"Endocrine Pathology" integrates classical diagnostic anatomic pathology with recent developments in immunochemistry and molecular biology in its approach to endocrine disorders. The book discusses not only a wide range of diseases commonly encountered in everyday clinical practice but also those uncommon conditions elucidated by such innovative techniques as ultrastructural immunochemistry and in situ hybridization.

Relaxin, perhaps more than any other hormone, has a varied history of eliciting enthusiasm, rejection, skepticism, and long lapses of neglect. Long after its discovery, it was a hormone in search of a physiological role in humans. Today, relaxin is implicated in mammary growth, development and function, ionotropic and chronotropic action on the heart, and angiogenic activity in both the peripheral tissues and the endometrium. It is best known for its effect on the uterus and the symphysis pubis in preparation for parturition. However, the literature suggests that not all functions occur in one species. This book describes how to obtain the necessary molecules or derivatives for research, reaching right into the design of new molecules for specific applications.

Carole Mendelson has assembled a panel of leading investigators to critically review the various classes of endocrine, paracrine, and neuroendocrine factors that play a role in the regulation of lung development and surfactant production. Special attention is accorded the actions of glucocorticoids in lung development and the synthesis of surfactant glycerophospholipids and proteins. Also extensively treated are the roles of cell-cell interactions and the elaboration of various growth factors and bioactive peptides in pulmonary cell differentiation, gene expression, and pathophysiology. State-of-the-art and comprehensive, Endocrinology of the Lung constitutes a powerful new standard guide that illuminates the complex endocrinology of the lung for all those actively investigating hormone action in pulmonary biology and medicine today.

In the years since the initial discovery that blood from diabetic patients contains increased amounts of a posttranslationally gluco sylated form of hemoglobin (hemoglobin Ale)' an impressive number of studies have clarified and expanded the use of glycohemoglobin levels to assess disease status. Many other structural proteins have been shown to undergo similar changes, including proteins from tissues most commonly affected in diabetes (e.g., lens, aorta, peripheral nerve, basement membrane). Thus, the nonenzymatic glycosylation of hemoglobin emerges as an invaluable model for the pathogenesis of certain chronic diabetes complications. In addition to reviewing a wealth of investigative possibilities in the area of these chronic complications-including eye, kidney, nerve, and vascular disease-Dr. Cohen indicates how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for maintenance of long-term euglycemia. Dr. Cohen is an endocrinologist and diabetes specialist whose research activities have largely focused on the chemistry and metabo lism of the basement membrane in diabetes. This superb monograph on nonenzymatic glycosylation clearly shows the major trends of her past and present research and clinical activities. This book is beautifully written and a pleasure to read. It provides great insight into the mechanisms of the pathogenesis of the oom- vii viii Foreword cations of diabetes and should be of immense value not only to basic and clinical investigators, but also to internists, diabetologists, and endocrinologists in clinical practice."

It has been a challenge for us to edit this volume of Endocrinology and Metabo lism: Progress in Research and Clinical Practice. The topic of the pathogenesis of insulin-dependent, type I diabetes mellitus is particularly appropriate for this series, since advances in this area have been made, to a large extent, by applying state-of-the-art laboratory techniques to clinical samples. Over the last several years, a number of lines of evidence have been gathered, suggesting that classic type I diabetes mellitus results from the autoimmune des truction of pancreatic beta-cells in genetically susceptible individuals. This hypothesis is particularly appealing because it offers a rational approach to the prevention of diabetes by immunosuppression. We have tried to present a balanced, authoritative summary of the information currently available to support the autoimmune hypothesis for the pathogenesis of human type I diabetes, to place this information in historical perspective, to include relevant information from animal models of type I diabetes in which more invasive experimentation is ethical, and, finally, to update the reader on the current status of attempts to intervene in the progression of diabetes with immunosuppressive drugs. New York, New York Fredda Ginsberg-Fellner Robert C. McEvoy Contents Preface.. . . .. .. .. . . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . .. . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . 1. The Autoimmune Hypothesis of Insulin-Dependent Diabetes: 1965 to the Present . . . . . . . . . . . . ..................... . . . . . .

In recent years, a series of excellent textbooks have been published dealing with pathology of the thyroid gland. The present volume of CURRENT TOPICS IN PATHOLOGY provides further information for both pathologists and clinicians interested in the thyroid gland. The contributions deal with surgical pathology of the thyroid as well as with basic aspects of thyroid metabolism, hormone transport, and growth factors in thyroid cells. The topics covered in this book should mainly be considered as adjuncts to common textbooks on thyroid pathology. The contributions should help pathologists in their routine diagnosis and should stimulate further thyroid research.

This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume."

Nineteen cutting-edge review articles by leading authorities provide a comprehensive overview of the normal function of the pituitary and of the diagnosis and treatment of pituitary disorders. Topics range from normal hypothalamic-pituitary interactions and the processes that disrupt them to new advances in pituitary imaging and appropriate surgical intervention in various pituitary disorders. Among the diseases discussed are congenital hypopituitarism, deficiency states, strategies for evaluating patients with hyperprolactinemia, Cushing's syndrome, acromegaly, and glycoprotein pituitary tumors.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re sulted in a family of peptides with GH releasing properties. These com pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest."

Quality of the Body Cell Mass presents proceedings of the International Symposium on Quality of the Body Cell Mass held in Fort Lauderdale , Florida. The text describes the states of the art of making measurements of body composition, including the methods and their interactions, and provides examples of applications that describe individual studies in the clinical areas of AIDS, obesity, osteoporosis, aging, wasting, and chronic disease. More than 50 illustrations complement the text.

A central concept in the evolutionary theory of senescence is the idea that ageing results from life-history trade-offs. In particular, the disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. Comparative studies among mammalian species confirm that cells from long-lived species appear to have a greater intrinsic capacity to withstand stresses than cells from short-lived species. Childbearing at older ages has become increasingly common in modern societies because of demographic changes, medical progress and personal choice. While the detrimental effects of late reproduction on infant mortality and genetic diseases have been well documented, little is known about the possible postponed detrimental effects of late parenting.

Different genetic diagnostic and treatment options are used worldwide to improve routine IVF procedures for the benefit of patients. This handbook updates the new genetic diagnostic technologies that have been translated to the clinic, aiming to improve outcomes in the clinic and result in a healthy baby in the home. Chapters cover the use of genetic technologies in a personalized manner to unravel the possible genetic risks for the couple wishing to conceive, in terms of sperm, the embryo, the endometrium, miscarriage, and finally the fetus. This expanded new edition covers the range of the latest genetic diagnostic technologies being translated into practice internationally to improve routine IVF procedures for the benefit of patients. Bringing together international experts to discuss their work, this text gives a context for the developments in this very fast-moving area of research and offers a comprehensive and rounded appraisal of hot topics.

The growth and function of many tissues are influenced by hormones. Therefore it is quite understandable that hormones play a role in the development and treatment of malignant tumors. Numerous publications address this topic; however, the results of many studies are controversial and have not been unequivocally accepted. For nearly 50 years the carcinogenic effect of steroid hormones has been under debate, and their therapeutic value a matter of discussion for equally as long. The present volume concentrates on substantiated data first obtained from the study of tumors developing from hormone regulated or hormone-producing tissue, e.g., the thyroid, adrenal glands, prostate, and the female genital tract. Through a joint approach from the field of molecular biology, biochemistry, and histopathology, advances in the management of these tumors have been elaborated. Another exciting example is the endo nuclear diagnosis of adrenal tumors. Antihormones, i.e. antian drogens or GnRH analogues have proved to be important indeed since they exhibit a destructive effect on prostate carcinomas and breast cancer. Further improvements can be expected in the localization of hormones in tumor tissue by specific antibodies. A special chapter is dedicated to the diffuse endocrine cell system (DECS), the clinical significance of which has mainly become obvious in the gastroenteropancreatic tract.

Calcium metabolism is regulated by three specific hormones: parathor- mone, calciferol metabolites, and calcitonin. Cyclic AMP also plays an important part in calcium regulation, and its concentration in urine can be taken as a measure of parathyroid function. Methods for quantitative measurement of, e.g. calcium-regulating hormones and vitamin D metabolites as well as of cAMP are absolutely necessary for safe differential diagnosis of diseases of the parathyroid like hypo- and hyperparathyroidism. In this monograph all presently available methods are summarized as to whether they can already be obtained as test kits or are still being tested. Radioimmunoassays for the various peptide fragments such as 53-84, 44-68, 28-48, and 1-34 are described, as are immunochemiluminescence methods and adenylate cyclase bioassays. The same is true for the vitamin D metabolites, where the various assays for calcidiol and calcitriol such as HPLC, protein-binding assay with second antibody separation, and double antibody RIA are dex scribed. Finally, determination of calcitonin and cAMP is discussed in detail. This is a practically and clinically oriented monograph for working in the fields of internal medicine, endocrinology, and laboratory medicine.