Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye disease. Each chapter is written by an expert and truly represents the current state of the art on the particular topic. This book can therefore almost be considered a textbook on this enigmatic disorder. Recent Developments in Graves' Ophthalmopathy is designed for all those interested in this disease, including basic scientists, clinical endocrinologists, ophthalmologists, radiotherapists, and orbital surgeons. The book gives a comprehensive overview of all aspects of Graves' ophthalmopathy. Subjects covered include the pathology of Graves' eye disease and the controversial views on its autoimmune pathogenesis; assessment of the eye changes using reliable measurements; medical management of Graves' eye disease with an overview of the many treatment options available to the clinician, including orbital radiotherapy and other immunosuppressive treatments; management of the thyroid disease; and finally, the techniques for performing various surgical procedures, which are explained and illustrated.

Since the late 1960s, there has been an acceleration of research focused on understanding how the efferent ducts, the epididymis, and the vas deferens function with respect to the maturation and storage of spermatozoa and as hormone dependent tissues. Another major interest in the epididymis is that it is an attractive target for the development of male contraceptives. There are well over 16,000 peer reviewed articles in the literature on these tissues, their structure, gene expression, protein synthesis and function. Regular international meetings have been initiated that are dedicated to this field. Thus, there is an urgent need for a comprehensive reference volume that spans every facet of epididymal biology, from historical background to the most current results, from basic cell and molecular biology to clinical issues. Well-established experts from every part of the world have contributed to this volume. By necessity, each author was given page limitations so that many topics are not dealt with exhaustively. Whenever possible, references to more comprehensive discussion of specific topics are included.

Dr. Robert L. Jackson, Professor of Child Health at the Uni versity of Missouri-Columbia, decided to retire from clinical practice in 1977 and the Department of Child Health planned a con ference in his honor. The Thirteenth Annual MidweSt Conference on Endocrinology and Metabolism also was in the planning stages and scheduled for two days in the fall. It seemed appropriate to com bine the two into an expanded three-day conference. In view of Dr. Jackson's international reputation in the study and care of children with diabetes mellitus, the conference topic was not dif ficult to find. Experts in this field were delighted to be asked to speak at a conference in Dr. Jackson's honor. We selected a number of excellent speakers to survey the physiology and pathophy siology of pancreatic hormones and their effects in diabetes mel litus, to discuss current knowledge of the microvascular complica tions of the disease, and to put it all into the proper historical perspective of where we have been and where we are going. We think the conference achieved its objective to pay meaningful trib ute to a distinguished member of the scientific community. As with any conference, the conversion of the presentations and discussions to the printed page is a long and arduous process. Many manuscripts were completed well after the conference and references often are more recent than the date of the conference."

It is remarkable how much we take for granted the tremendous energy and vitality that the sun provides earth's inhabitants. As we enter the new millennium, it is worthwhile to review how our ancestors perceived the biologic effects of sunlight, and how science and medicine have advanced our knowledge about the biologic effects of light. At the turn of the century, a multitude of investigators explored the use of sunlight and artificial radiation for treating a multitude of diseases. These explorations gave rise to photodynamic therapy, phototherapy, and chemophototherapy. However, enthusiasm for using sunlight and artificial radiation to treat disease was dampened with the birth of pharmacology. It was the goal of the Fifth International Arnold Rikli Symposium on the Biologic Effects of Light, held in Basel, Switzerland, on November 1-3, 1998, to review the history of phototherapy and have some of the world's leading experts on the biologic effects of light provide new perspectives on the positive and negative effects of light. The general topics included a broad range of biologic effects of sunlight, artificial ultraviolet radiation and electromagnetic radiation. Special sessions on radiation and vitamin D and bone health, photoimmunology, biopositive effects of UV radiation, effects of electromagnetic currents and fields, and ocular and non-ocular regulation of circadian rhythms and melatonin, should be of particular interest to readers of Biologic Effects of Light.

The idea for this book developed as an outcome of a multidisciplinary sym posium entitled "Pituitary Adenoma Update" that was held at Tufts-New En gland Medical Center in April 1977. The purpose of that symposium was to put together our current knowledge of the cause of pituitary tumors and discuss the diagnostic evaluation and management that was now appropriate, in light of the rapid advances that had taken place so recently in this area. Those of our colleagues who had presented papers at the symposium, as well as a number of others, were invited to contribute to this volume, which should serve as a presentation of the "state of the art" on all aspects of pitu itary tumors. We felt that such a book would be of value to endocrinologists, neurosurgeons, neuroradiologists, and pathologists who are involved in the investigation or care of patients with pituitary disorders. For a number of reasons, a review of pituitary adenomas seems particu larly timely. Rapid advances have taken place coincidentally in the fields of neurosurgery, neuroendocrinology, neuroradiology, neuropathology, and neuropharmacology. Seven major developments in these areas have occurred independently and almost simultaneously that have virtually revolutionized our approach to pituitary adenomas.

Leading medical specialists critically review for the general practitioner the latest techniques for the clinical management of diabetic neuropathy. These authoritative contributors focus on the practical aspects of diabetic neuropathy and describe in detail the treatments that are currently available or expected to become available in the near future. They also include concise discussions of the causes of diabetic neuropathy and highlight the relatively unknown features of neuropathy that can significantly impact a patient's life. Comprehensive, up-to-date bibliographies at the end of each chapter provide an opportunity for the interested physician to gain a more detailed picture of a particular topic. This book offers family physicians, internists, endocrinologists, podiatrists, cardiologists, neurologists, and gastroenterologists an authoritative practical guide and a vital day-to-day reference source for the management of their neuropathic diabetic patients.

After a decade or longer, approximately one-third of individuals with either type 1 or type 2 diabetes commence a downhill course in which decreasing renal function and failing vision define a Renal-Retinal Syndrome, dominating all aspects of life and presaging early death. Only a generation ago, survival after onset of end-stage renal disease (ESRD) in diabetes was limited because rehabilitation was preempted by blindness, limb amputation, stroke, and heart disease. By 1998, however, team management has improved the outlook, with preserved sight and return to work and home responsibilities, usually for a decade or longer, following kidney transplantation and laser photocoagulation. Recognition of the critical requirement for blood pressure regulation and metabolic control are central themes in management. In this unique book, the accomplishments of ophthalmologists, nephrologists, diabetologists, transplant surgeons, and basic scientists are blended into a strategic approach that may be readily applied by all those caring for diabetic patients. Each of twenty-one presentations suitable for primary care physicians, as well as for subspecialists concerned with macrovascular and microvascular complications of diabetes, is placed in perspective by an introductory editorial analysis. Promising near-term innovative therapies, including insertion of genetically engineered beta cells or polymer-coated islets of Langerhans, interdiction of kinins that promote retinal angiogenesis, and prevention of synthesis of advanced glycosylated endproducts (AGEs), are presented in detail. While comprehensive care of diabetic patients reflects multiple incremental advances that in sum afford major benefit, this text envisions further remarkable changes likely to suppress and possibly entirely prevent the Diabetic Renal-Retinal Syndrome.

Growth Hormone is a fitting addition to the Endocrine Updates Series. The aim of these publications is to provide the clinician with cutting-edge, yet succinct, access to the latest advances in endocrinology. Current interest in this rapidly evolving area of endocrinology makes this a timely and important update. Growth Hormone joins Dr. Fagin's Thyroid Cancer in continuing the standard of excellence as the fourth volume in this series of topical updates. Shlomo Melmed, MD, Series Editor, Endocrine Updates Ten years ago, many endocrinologists were still skeptical that growth hormone (GH) played an active role in adult metabolism. This is, perhaps, surprising given that GH deficiency (GHD) in adulthood had been `recognized' as long ago as the 1960s. During the last ten years studies have shown that GHD in adulthood is a far-reaching syndrome associated with abnormal body composition, reduced bone mineral density with an increased fracture rate, increased cardiovascular morbidity and impaired cardiac function, as well as reduced exercise performance and decreased psychological well-being. Importantly, it is also clear, from placebo-controlled trials, that GH replacement therapy can normalize body composition, increase bone mineral content and improve the cardiovascular risk factor profile. GH replacement therapy also improves cardiac performance and exercise capacity, increases muscle strength and improves well-being and quality of life. The aim of Growth Hormone is to provide a critical update of current knowledge about adult GHD and the future role of GH/IGF-1 in adult medicine. For this purpose, contributions from a number of research groups have been invited. It is my hope that the book may not only serve as an introduction to the field, but also stimulate further research within this exciting area.

In a rapidly evolving and extremely important area of medical science, it is often difficult for the student, teacher, and researcher to keep abreast of all the important advances. The purpose of Molecular Biology ofDiabetes, Parts I and II is to bring to these individuals the latest knowledge of diabetes-related research in a comprehensive, yet concise manner. To this end, we have assembled chapters, written by most of the world's experts in the field, that we believe compre hensively survey and synthesize a coherent understanding of the subject. Studies of the etiology of type I and type II diabetes are extremely exciting and essential, since we hope to one day prevent the disease using gene therapy. These aspects are covered in Molecular Biology of Diabetes: I. Autoimmunity and Genetics; Insulin Synthesis and Secretion. In type II diabetes, an abnormality in pancreatic secretion exists concomitantly with peripheral insulin resistance. This abnor mality of insulin secretion is believed to be related to a defect(s) in glucose sensing. Uncoupling of glucose sensing from insulin secre tion may be the crucial step in the pathogenesis of noninsulin-depen dent diabetes. In this volume, we have invited authors to describe their studies on all known factors affecting ~-cell function, including autoimmunity and genetics of diabetes, as well as molecular mecha nisms of insulin synthesis and secretion. In the last few years, the most rapidly advancing area of research in diabetes has been, in fact, related to insulin action.

Genetics of Diabetes Mellitus is intended to be a resource for both researchers in the field as well as endocrinologists, diabetologists, and geneticists who seek to learn more about this rapidly changing and important field. The text contains chapters from experts in the area who review aspects of the genetics of both type 1 and 2 diabetes mellitus as well as various syndromic forms of diabetes. The chapters are approachable for those who are not experts in the field of genetics but also comprehensive, so as to serve as an important resource for researchers interested in the genetics of diabetes mellitus. A description of basic concepts of the genetics of complex diseases like type 1 and type 2 diabetes is provided as background. Type 1 diabetes is addressed in chapters exploring genetic determinants that affect the autoimmune process characteristic of type 1 diabetes, the role of the insulin gene in the pathogenesis of type 1 diabetes and additional genes that may impact upon the risk of type 1 diabetes. The impact of genetic determinants on the pathophysiology of type 2 diabetes is covered, as are chapters that address specific genes that are important for the development of type 2 diabetes. Finally, syndromic forms of diabetes, including Maturity Onset Diabetes of the Young and mitochondrial diabetes, and the insight that these disorders provide into more common forms of diabetes are reviewed. Thus, this comprehensive and up-to-date text will serve as an important resource for those actively engaged in research in this area and clinicians treating these patients to provide an up-to-date entree for those seeking to become more knowledgeable in the area.

Growth Hormone and the Heart endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. Growth Hormone and the Heart will be a useful update of the research produced in the field of cardiovascular endocrinology. The Editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.

This volume is a collection of the most significant contributions to the 4th International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE: STRATEGIES OF PREVENTION OF CORONARY HEART DISEASE, CARDIAC F AlLURE, AND STROKE held in Washington, D. C. in April 1997. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological, clinical, and biological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of populations in the industrialized countries. The evidence that a combination of risk factors confers a very high risk of developing cardiovascular diseases, is of pivotal interest in the process of detection of patients who will benefit the most from pharmacological treatment. Many recent epidemiological data identifying the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline atherosclerosis as a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure rheologic forces, carbohydrate tolerance, and thrombogenic factors, including fibrinogen, tissue factor, PAl-I, and homocysteine. Furthennore, the risk associated with anyone of these risk factors varies widely depending on the level of the associated atherogenic risk factors. Hyper cholesterolemia and hypertriglyceridemia, for instance, are more common than would be expected by chance among hypertensive patients.

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it will serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

It is an authentic privilege to have the opportunity to assemble and edit a new volume on "Prolactin," the first in several decades to be devoted to this fascinating hormone in all its aspects. The obvious clinical rationale for understanding prolactin (PRL) is the frequent occurrence of prolactinomas, the most common type of pituitary tumor. Fortunately, medical management of prolactinomas can be based on our under standing of the physiology of hypothalamic control of the lactotroph. Armed with this knowledge, therapies for proiactinomas are highly successful and well tolerated. Be cause of the historical and practical importance of knowledge regarding the hypothala mus-Iactotroph axis, the first chapters of this volume are dedicated to reviewing the physiology, development, and cell biology of lactotroph regulation. Chapters focusing on prolactinomas and related clinical issues follow these. PRL is the primary hormone that is responsible for "parental care" in many verte brate species. This reproductive strategy is not unique to mammals, but it has devel oped through evolution to be the central distinguishing feature of the mammalian life cycle. Among the mammals, mice have become the most effective research species in recent years. This can be traced to the development of a wide range of methods for manipulating mouse genetics, and thereby influencing development, physiology and behavior. Mice also provide a profound illustration of the physiological challenges faced in maternity. Female mice undergo a post-partum estrous, and often are both pregnant and lactating simultaneously.

Aaron I. Vinik, M.D., Ph.D. I IEastem Virginia Medical School The Diabetes Institutes Norfolk, Virginia 23510 This symposium, held in June 1991, was a gathering of international scientists to exchange their views on current concepts of cell growth and differentiation. Each scientist was asked to present a topic of their research related to cell growth and regeneration and to participate in a round table conference elaborating on current knowledge and sharing their experiences. By furthering this promising area of endeavor, a means of understanding ontogeny of cell development and of providing insights into tumor biology would prevail. Of prime importance was the anticipation that new information from a better understanding of the normal evolution of the pancreatic islet would generate alternative approaches to curing diabetes. This forward serves as a short introduction to the concept of pancreatic islet regeneration and the models currently in use to study the process. DEVELOPMENTAL ORIGIN OF ISLETS DURING EMRYOGENESIS The developing pancreas appears as a protrusion from the dorsal surface of the l embryonic gut. The different islet cell types appear sequentially during development in vivo. It therefore seems reasonable to propose that coordinated growth is dependent upon specificity of growth factors.

In September, 1977, at a conference organized by Dr. Kenneth McKerns in Northeast Harbor, Maine, USA, I was asked by the Editorial Committee of the Biochemical Endocrinology series to investigate the possibility of organizing the next meeting in France. I proposed a subject which is in the area of my research interest, and this subject was accepted. On arriving back in France, I first looked for an appropriate place for the meeting, and the Chateau de Seillac was chosen in accordance with many objective criteria. We know that all who attended the meeting held in Seillac enjoyed this quiet and charming place in the Loire Valley. The next step was to choose some experts in the field who would contribute to the monograph and present their papers at a conference for the purpose of generating discussions. The action of the local committee, composed of Dr. A. Tixier-Vidal, Dr. Claude Kordon, and me, was crucial in this respect. The local committee proposed the program for the meeting and a list of the majority of contributors to be invited. I wish to thank Dr. Tixier-Vidal and Dr. Kordon for their invaluable assistance.

In September of 1977 scientists from many countries met at the Asticou Inn in Maine to present and discuss papers written especially for this monograph. The presentations were informal and directed to the special interests of the audience in order to generate discussions. The authors, many of whom are pioneers and leaders in their field, then had the oppor tunity to revise their contributions, which were brought together with the edited discussions to form this volume. The basic research studies presented here are important because of the essential role of gonadotropins in regulating the ovary and testis. This monograph will therefore be of interest to those concerned with fertility regulation, population control, possible new methods for contraception, and to those concerned with reproduction in domestic animals. Re searchers in other fields may find this monograph useful, as it has been de termined that gonadotropins are secreted by many tumors and are im plicated in many cancers. Human choriogonadotropin also seems to be found in most, if not all, cells of the human body. The significance of this, however, is unknown."

Calcium-Sensing Receptor provides an overview of various aspects of the calcium receptor's biochemistry, physiology and pathophysiology that is suitable both for those who have been working in the field of Ca2+0-sensing as well as those who are new to this discipline. Calcium-Sensing Receptor is the nineteenth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

An enormous amount of research effort has been directed toward elucidating the mechanism by which substances are extruded from cells; and reviews have been written and symposia held in order to systematize the plethora of evidence made available. However, the approaches employed to study the secretory process have been so diverse that it is difficult, if not impossible, for one individual or even a group of individuals to keep abreast of all aspects of the field and to analyze them critically. Thus I undertook the writing of this volume with a great deal of trepidation. In searching for some starting point, I naturally considered as my primary focus the role of calcium in the secretory process, which has occupied my research interests for the past 13 years. But since so much experimentation has been carried out on this and related topics during the last decade or two, I felt it was still necessary to visualize this venture from two alternative ap proaches: (1) a more general one, which would cover the subject of calcium and the secretory process from a broad perspective, but of course not in great detail, and (2) a more specific one, restricting coverage to carefully defined limits but with comprehensive analysis of limited topics. The final course undertaken appears to lie somewhere between these two extremes."

Brain Neurosecretory Cytokines: Immune Response and Neuronal Survival summarizes the biological and chemical data of signal molecules of the brain neuroendocrine immune system, mainly proline-rich peptides, which play an important role in the regulation of immune response, neuronal survival, hematopoiesis, and adaptation. The author also describes the role of PRPs for the protection of neurons against neurodegenerative disturbances and diseases. Brain Neurosecretory Cytokines: Immune Response and Neuronal Survival will be of great aid to the researchers and students in various areas of neurobiological profile (neurochemistry, neuroendocrinology, neurophysiology, and endocrinology).

This book represents the proceedings from a conference that took place in Dallas in the spring of 1999 which was entitled "Pediatric Gender Assignment - A Critical Reappraisal". Some participants rightfully argued that the conference really focused on the issue of pediatric gender assignment, and that reassignment was not applied in most cases. Their comments were reflected in the title of this monograph. This multidisciplinary meeting was sponsored by a conference grant from the National Institutes of Health, and a broad inquiry into this complex topic took place from many points of view. Basic scientists offered insight into mechanisms of sexual differentiation of the gonads, physical phenotype and imprinting of the central nervous system. Endocrinologists reviewed their experience in diagnosis and management, surgeons described traditional as well as innovative approaches, and there was strong representation from the ethical and behavioral sciences. In putting together such a panel, it was essential that we identify a cast of speakers who could address their viewpoints with strong convictions, and yet not let their passions render the meeting counter productive. We were not disappointed. While many differing points of view were firmly expressed by the panelists and audience, all viewpoints were accorded the respect they deserved. The concept behind the meeting and this book really originated in 1997 shortly after Diamond and Sigmundson published their long term follow up study of the John/Joan case.

This book tells the story of diabetes, from ancient times to today, and provides an accessible introduction to the cause, treatment, and impact of the disease.Diseases have a history, and understanding that history helps us understand how best to treat and control disease today. Today's students are confronted with a panoply of often-frightening illnesses and afflictions - the Biographies of Disease series provides necessary information to understand the origin of various maladies, how they impact contemporary society, and how doctors and researchers from around the world are fighting to devise treatments to alleviate or cure these diseases.This volume, Diabetes, covers a disease that has been a common affliction from the beginning of recorded history, but has been increasing in its impact because of changes in diet and exercise, especially among the young. Diabetes examines all aspects of this disease, including: the diagnosis and treatment of diabetes from the ancient period to the present day; the definition of the various types of diabetes, and the role of glucose and insulin; diagnosis and treatment, with an emphasis on prevention for those at risk; the cultural impact of the disease - on individuals, on families, and on the economy; and, the state of current research on new forms of insulin, blood glucose meters, transplants, and weight control.The volume includes a glossary of important terms and a bibliography of accessible works that discuss the disease.

During the last ten years, the diagnostic approach to disorders of bone and mineral metabolism has benefited considerably from the development of radioimmunoassay and competitive protein- binding techniques for measurements of circulating parathyroid hormone, calcitonin, and biologically active vitamin D me- tabolites. Accumulated experiences with radiogrametrical and densinometric methods of quantitating appendicular bone mass now facilitate the detection of changes in bone mineral content heretofore unrecognized by routine roentgenographic vertebral analysis. During this same decade, the diagnosis of metabolic bone disease and the skeletal response to remedial therapeutic ma- neuvers have also been facilitated by the routine application of the bone biopsy. Improvements in tinctorial techniques, stan- dardization in methodology essential for adequate preparation of thin undecalcified specimens, and the incorporation of tetracy- cline bone formation or mineralization "markers" should now herald the "routine" use of this diagnostic procedure. Moreover, the compilation and ready availability of reference morphometric data, spanning the prepubescent years charac- terized by skeletal growth and remodeling and the later senes- cent period during which bone loss normally proceeds in an un- 7 8 FOREWORD relenting fashion, allow adequate differentiation between normal age-sex-related changes in skeletal turnover attendant on skeletal maturation and aging and acquired or inherited de- rangements in bone metabolism.

Autoimmunity is the most common cause of endocrine disorders. This volume provides an up-to-date summary of recent advances in this important field. In addition, it describes developments in our understanding of conditions such as vitiligo and pernicious anaemia which are frequently associated with autoimmune endocrinopathies. There is a detailed review of animal models of endocrine disease which have contributed greatly to current knowledge. Furthermore, the aetiology, pathogenesis and treatment of the clinical disorders are discussed in depth. The book will be of interest to anyone working in the areas of endocrinology and immunology.

This book includes the most significant contributions of the First International Symposium on "Multiple risk factors in cardiovascular disease", chaired by Professors A. V. Chobanian (Boston), A. M. Gotto Jr. (Houston), c. Lenfant (Bethesda), R. Paoletti and A. Zanchetti (Milan), held in Washington DC, 10-12 December 1990, which focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological evidence that individuals from industrialized countries often possess two or more risk factors which synergically increase the global risk profile. The evidence that isolated vascular risk factors are not commonly found in high risk patients but more often a combination of risk factors are detected, is highlighted. Many recent epidemiological data identifying the intrinsic and environ mental factors contributing to the development of atherosclerosis are discussed. These results, in parallel to basic and clinical research, underline how atherosclerosis is a complex and multifac torial process involving the influences of lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors (fibrinogen and platelets). Atherosclerosis is markedly accelerated by other risk factors, more so in the presence of concomitant hypercholes terolemia, hypertension, diabetes, upper body obesity. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.