The sum of clinical problems caused by diabetic renal disease has been steadily increasing since the first edition of this book was published in 1988. The years since have seen tremendous progress in research activities. Importantly, this also includes improvement in the treatment programs to prevent end-stage renal failure. It has become clear that the diabetic kidney is extremely pressure-sensitive, responding to effective antihypertensive treatment by retarded progression of disease. Some agents may be more beneficial in this respect than others, although effective blood pressure reduction per se is crucial throughout the stages of diabetic renal disease. However, the prime cause of diabetic renal disease is related to poor metabolic control and it is now documented beyond doubt that good metabolic control is able to postpone or perhaps even prevent the development of renal disease. However, in many individuals we are not able to provide such a quality of control that will prevent complications, and therefore non-glycaemic intervention remains important.Maybe in the future non-glycaemic intervention will become the most important research area in diabetic nephropathy. Much information is now available on the exact mechanisms behind poor metabolic control and development of renal disease. It is likely that a combination of genetic predisposition and metabolic and haemodynamic abnormalities explain the progression to renal disease, seen in about 30% of diabetic individuals. Much of this development probably relates to modifiable genetic factors, such as blood pressure elevation or haemodynamic aberrations. However, mechanisms related to the response to hyperglycaemia are also of clear importance, as is the possibility that these metabolic or haemodynamic pathways may be inhibited. This volume reviews older data as well as the progress seen within the research on diabetic nephropathy over the last five years and describes the state of the art of the development.

"Frontiers In Thyroidology" assembles the prize lectures, symposia, and papers presented during the Ninth International Thyroid Congress in Sao Paulo, Brazil in September, 1985. This book represents the State-of the-Art in thyroid studies with its continuous expansion into the areas of immunology, molecular biology, clinical and environmental medicine. As its name also indicates, the material compiled in this volume defines important questions to be answered in basic and applied aspects of the thyroid. So, this book clearly demonstrates the rewards, excitement, and challenges posed by the thyroid gland. Once again, the thyroid gland, through its unique and important functions and implications in health and disease, has been able to congregate scientists throughout the world to communicate their findings, to share their expertise and experiences, and to strengthen their bonds of friendship and commitment to make a better world through their work. This publication consists of 309 papers in 19 different topics. The prize lectures and symposia review and update our knowledge in basic and clinical aspects of exceptional interest in the thyroid field. "Frontiers in Thyroidology" adds to a series of publications from previous interna tional thyroid meetings which includes: "Advances in Thyroid Research", London, 1960; "Current Topics in Thyroid Research", Rome, 1965; "Further Advances in Thyroid Research", Vienna, 1970; "Thyroid Research", Boston, 1975, and "Thyroid Research VIII", Sydney, 1980. We would like to express our gratitude to Mrs. P. Langford and Drs.

We have witnessed a rapid development within the field of the kidney and hypertension in diabetes mellitus. A significant amount of work within the traditional areas has been published, and several new dimensions are now being developed, mostly in the experimental setting. These dimensions are discussed in several chapters of this new edition, The Kidney and Hypertension in Diabetes Mellitus, Fourth Edition. This volume endeavors to cover all aspects of renal involvement in diabetes. It is written by colleagues who are themselves active in the many fields of medical research covered in this volume: epidemiology, physiology and pathophysiology, laboratory methodology and renal pathology.

The study of the insulin-like growth factor (IGF) family has become an exciting area of investigation. Initially, this family consisted of ligands (insulin, IGF-I and IGF-m and receptors (the insulin receptor, the type I or IGF-I receptor and the type II or IGF-IYM-6-P receptor). Subsequently, it was discovered that six specific binding proteips (lGFBPs 1-6) playa major role in the actions of this growth factor family. In addition, there are now more potential receptors when one considers the possible roles of the insulin-receptor related receptor (IRR) and hybrid receptor dimers composed of insulin and IGF-I receptor (half-receptors). Another important aspect of this area of research is the realization that the IGFs are not only essential for normal growth and development but, in addition play an important role in the normal specialized function(s) of all tissues of the body, including the nervous system, skeleton, reproductive system, kidney, and the immune system, to name but a few. The development of recombi tant human IGF-I for clinical testing has been a major breakthrough for investigators. Potential uses include wound healing, reversal of catabolic states, diabetes, bone remodeling, recovery from acute renal failure and many others. will determine both its use and its potential hazards.

The aim of this book is to provide clear and concise information about the safe prescribing of insulin both subcutaneously and intravenously. It provides information on the different types of insulin, the delivery devices, side effects of insulin and, most importantly, on rational dose adjustment.

The Eleventh Midwest Conference on Endocrinology and Metabol ism in September 1975 brought together a number of leading invest igators in the areas of steroid, peptide, acetylcholine, and cate cholamine hormone receptor studies. This book is based upon the reports of investigations into hormone receptor biochemistry and physiology presented at the Conference as well as on the ensuing discussions. However, many of the manuscripts were written after the Conference. Because of this, the reader will find that some literature references and results of i vestigations are more up to-date than the Conference date would suggest. Perusal of this and previous volumes will attest to the high quality of this annual conference, due primarily to the efforts of the Planning Committee. We also acknowledge the superb efforts of the staff of Conferences and Short Courses for their assistance in organizing the Conference, and Mrs. Linda Bennett for expert sec retarial assistance in the typing of the book. Last, but certain ly not least, we express our appreciation to the various organiza tions that provided the necessary financial assistance. Leonard R. Forte John M. Franz David M. Klachko vii Contents The Receptor Concept: Prejudice, Prediction, and Paradox. . . . . Oscar M. Hechter Discussion. . . . . . . . . . . . . . 41 DeGroot, Hechter, Campbell, Freed, Barnawell, Morgan, Siegel Nuclear Receptors for Thyroid Hormone . 45 Leslie J. DeGroot 69 Discussion ............ ."

Since 1948, the date of publication of Hormones and Behavior by Dr. Frank Beach, this hybrid area has received a great deal of attention from scientists representing various allied fields. As a result, the data and publications dealing with hormones and be havior have increased geometrically and on an annual basis. More recently, a number of review articles and short volumes dealing with aspects of hormones and behavior have been published. How ever, there seemed to be an overwhelming need for a synopsis of the major topics in a unified and integrated form. Thus, the reason for this edition. In these two volumes, we hope we have presented a critical assessment of the various interrelated areas dealing with hormones and behavior. In some instances, we have minimized the presenta tion of certain aspects of psychoendocrinology. This was a con scious effort since some areas have received competent coverage in other volumes. In other instances, we have presented hitherto seldom mentioned material. For example, we are presenting coverage of the general areas dealing with hormones and behavior in aging and the aging process, mental illness, early experience, motivation, genetics and personality. In some instances, the available data is overabundant; in others, the data is scarce. However, we hope that an evaluation of this situation stimulates further interest and further collaborative research where needed.

Although physiological and anatomical evidence had clearly indicated for many years that the secretion of anterior pituitary hormones is under control by the central nervous system, it is only recently that the isolation and determination of structure of three hypo- thalamic hypophysiotropic hormones have been accomplished. This has brought the concept of neurohormonal control of adenohypophyseal function into precise biochemical and chemical terms. The relative ease of synthesis of TRH (thyrotropin-releasing hormone), LH-RH (luteinizing hormone-releasing hormone), somatostatin and their analogues has opened a new era in the field of endocri- nology and has led to a rapid expansion of our knowl- ge of the control of anterior pituitary function. The rapid evolution of fundamental and clinical research on hypothalamic hormones and the many potential clinical applications indicate the importance of inte- grating the knowledge gained in recent years. This is well illustrated in the Proceedings of the International Symposium on Hypothalamus and Endocrine Functions held in Quebec City on September 21-24th, 1975, which indi- cates that impressive progress has been made in large variety of aspects of hypothalamic hormone research.

To obey the precepts of therapeutic rationality, we should avoid treating the "effect" when there is a way to attack the cause. But what is the cause of diabetes? Diabetes is a molecular disease, that is, a disease in which important cellular components are seriously impaired. Eventually, the activities or the products arising from the impairment find expression in various ways, finally culminating in the abnormalities of diabetes. How early is early enough to attempt to delay this sequence of events? What will provide us with the basis to explore ways and means of halting the progression of the pathological process? What are the new approaches for the treatment of early diabetes? The Fourth International Symposium on Early Diabetes, sponsored by the Diabetes Center of the New York Medical College, held in Algarve, Portugal in November 1978, from which this book evolved, attempted to answer some of these questions. A list of the participants, including their affiliations, will be found preceding the index. Rafael A. Camerini-Davalos v Acknowledgments To our sponsors, U.S.V. Pharmaceutical Corp., Pfizer Pharmaceuticals, Ames Company, Hoechst, Frankfurt; supporters, Boehringer, Manheim, Laboratoires Servier, Nordisk Laboratory, The Upjohn Company, Eli Lilly and Company, F. Hoffman La Roche; and contributors, Bayer A. G. Leverkusen, McNeil, Novo Research Institute, ICI Belgium, Hope for Diabetics Foundation, New York, we express our appreciation for the financial support which made possible the Fourth International Symposium on Early Diabetes. THE ORGANIZING COMMITTEE Rafael A. Camerini-Davalos, M.D.

During the last two decades, progress in steroid hormone research has resulted in the development of new approaches to contraception as well as diagnosis and treatment of endocrine disorders and cancers. Although significant advances have been made in the purification, characterization, immunochemistry and molecular biology of steroid receptors, the precise molecular mechanism of steroid hormone action has remained obscure. This book captures the detailed presentations made at the first conference on Steroid Receptors in Health and Disease held at Meadow Brook Hall, Oakland University in the fall of 1987. The purpose of this international con ference was to facilitate scientific exchange toward a better understand ing of the mode of action of steroid hormones. The scientific sessions consisted of poster presentations and state-of-the-art lectures, the latter of which make up this volume. The first chapter is meant to provide the reader with a more general background of the topics covered in the book, as well as to discuss certain theme-related issues that are either not yet well-established or accepted or are in the stage of infancy. It is hoped that this volume will serve as a useful treatise for students and investigators interested in basic and clinical aspects of biological regulation by steroid hormones. A task of this magnitude could not have been undertaken without the encouragement, advice and continued generous assistance of the members of the scientific committee. I am gratefully indebted to Drs."

This has been a year of substantial change for The Year in Endocrinology. The first change, though perhaps only a semantic one, nevertheless represents a landmark. Although last year's volume was designated as the first of an annual series, that seemed to me at the time merely a hope-a realistic hope, perhaps, but a hope, nevertheless. With the publication of this year's volume, however, this can accurately be said to be an annual series, one that we trust will fulfill a need and will therefore continue for years to come. Among other changes from last year's volume are some that were originally intended and others that were unintended. In the former category is the substitution of a chapter on water metabolism and vaso pressin, excellently prepared by Dr. Gary L. Robertson, for the chapter on paraendocrine syndromes that appeared last year. Chapters on these two topics will continue to appear on alternate years. Obviously, the non recurring chapter on a topic of special interest has also changed, and this year's comprises a comprehensive review of autoimmune endocrine dis ease by Drs. Jay Silverberg and Robert Volpe. The unexpected change results from the inability of Dr. Louis Avioli to continue as a member of the Editorial Board. Most fortunately, however, we have persuaded Dr. Charles R. Kleeman to join the Board and to be responsible for the chapter on the parathyroid gland and mineral metabolism. Dr. Kleeman has been assisted on the preparation of this chapter by his daughter, Dr."

The Center for Population Research of the National Institute of Child Health and Human Development began operations in August 1968 and is engaged in research dealing with health-related popula tion problems. We organize and support projects for the develop ment of new contraceptives and in the broad field of population research in the social sciences o The Center also supports a variety of projects dealing with the mechanism of action and medical effects of contraceptives now in use, particularly oral contraceptives and intrauterine devices. These studies were initiated several years ago at the specific direction of Congresso We were pleased, therefore, with the opportunity to help organize and support this important and timely conference on the "Metabolic Effects of Gonadal Hormones and Contraceptive Steroids," the subject of which forms an integral part of the Center's research program. April, 1969 Philip Ao Corfman Director Center for Population Research National Institute of Child Health and Human Development v PREFACE Progress in science is often associated with either a "sixth sense" or an inevitable timeliness. Both factors, perhaps, led the members of the Endocrinology Study Section of the National Institutes of Health to propose, in 1966, that an expanded view of the effects of gonadal hormones, in general, and the contra ceptive steroids, in particular. was needed. There had been ample evaluations of the clinical symptomatology, contraceptive efficacy, and effects on the reproductive system, but there was a dearth of information on their multiple systemic'metabolic effects."

In the summer of 1969, the first Workshop on Control of Renin Secretion was held at Stanford University. At its completion, it was suggested by many of those who attended that a second Workshop be planned in about two years time. Thus the second Workshop on Control of Renin Secretion took place and from this event the chapters in this book had their origin. The setting of this Work shop was the beautiful J & R Double Arch Ranch in Santa Ynez, California which houses the Kroc Foundation. The Foundation, through the kindness of its President, Dr. Robert L. Kroc, provided us with luxurious accommodations, excellent meeting facilities and an atmosphere extremely conducive to the exchange of scientific knowledge, both formally and informally. In addition, the Founda tion assisted financially in the travel expenses of three of our foreign guests and in the preparation of the manuscripts for this book. I know I speak for all of us who attended the Workshop in expressing our sincere gratitude to the Foundation and to Dr. and Mrs. Kroc and their staff. In addition, I personally, as organizer of the meeting and editor, wish to acknowledge the help of many others who made my job much easier. Drs. Davis, Ganong, Luetscher and Tobian kindly took on the jobs of chairing the four sessions and directing the lively discussions which followed each presentation."

Perinatal problems in thyroid gland physiology are common but complicated and present a diagnostic dilemma for the primary clinician. In December 1990, an international group of basic and clinical investigators gathered in Longboat Key, Florida to address these issues. The participants included internists, obstetricians, pedia tricians, neurologists, pathologists and basic scientists in cellular metabolism, endocrine physiology, and molecular biology. The presentations contained within this book bring together their most current and vital research related to the field of perinatal thyroidology. This book is based on the dynamic and fruitful exchange of the participants at the symposium. We are indebted to these individuals whose valuable insights and efforts are contained within this text. Barry B. Bercu Dorothy I. Shulman vii CONTENTS Session I Mechanism of Thyroid Hormone Action 1 Leslie J. DeGroot Thyroid System Ontogeny in the Sheep: A Model for Precocial Mammalian Species * . . * * 11 Delbert A. Fisher Pathologic Studies of Fetal Thyroid 27 Development * * * * * * * Douglas R. Shanklin Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, 47 and Behavioral Studies * * * * * * * S. A. Stein, P. M. Adams, D. R. Shanklin, G. A. Mihailoff, and M. B. Palnitkar The Thyroidectomized Pregnant Rat: An Animal Model to Study Fetal Effects of Maternal Hypothyroidism 107 Susan P. Porterfield and Chester E.

This volume is an outgrowth of a symposium held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975. This symposium was organized to bring together basic scientists and clinicians for the purpose of exchanging new ideas and the latest information in the area of Steroid Hormone Action and Cancer. The design of the symposium included both formal plenary sessions and informal roundtable discussion groups, the chapters of this volume being drawn primarily from these proceedings. During the last quarter of a century considerable progress has been made toward understanding the molecular mechanisms in volved in steroid hormone action. It now appears that the mechan sim of action of the four major classes of steroid hormones is qualitatively similar. Research during the past decade has demonstrated steroid hormone receptors in a variety of normal and neoplastic tissues. Receptor-containing neoplasms have been shown to be hormone-dependent and undergo regression when treated with hormone antagonists. Natural and synthetic steroids also have been employed for many years to successfully treat various types of cancer, for example: estrogens, androgens and progestagens for breast cancer; estrogens and progestagens for prostatic carcinoma; progestagens for endometrial carcinoma; and corticoids for leu kemias. All of these neoplasms have now been found to possess receptors for the steroids empirically used in their treatment."

As humans ventured into the twentieth century, the industrialized countries were confronted with the scourge of rickets. Although solariums were becoming common in the early 1900s and phototherapy was gaining popularity as a result of the awarding of a Nobel Prize to Finsen in 1903, it wasn't until 1921 when Hess and Unger demonstrated that rickets could be cured by exposure to sunlight that the healthful benefit of sun exposure appreciated. In 1941, Apperly (Cancer Research; 1: 191-195, 1941) noted that the occasional increased risk of skin cancer was associated with a decreased risk of many other more common and serious cancers. The alarming increase in the number of cases of skin cancer, especially melanoma, has caused great concern about the negative role of sunlight in health. The Sixth International Arnold Rikli Symposium on the Biologic Effects of Light was held in Boston, Massachusetts from June 16th - 18th, 2001. The goal of this Symposium was to focus on the very popular practice of tanning either by sunlight or by artificial light sources and the overall impact this practice has on health and disease. The program was organized by members of the Scientific Advisory Committee and my co-chair emeritus, Professor Ernst G. Jung. The Program Committee organized an outstanding state-of-the-art program that was enthusiastically received by the participants.

The human pancreas consists of two organs in one: the exocrine gland made up of pancreatic acinar cells and duct cells that produce digestive enzymes and sodium bicarbonate, respectively; the endocrine gland made up of four islet cells, namely alpha-, beta-, delta- and PP-cells that produce glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. While the physiological role of exocrine p- creas is to secrete digestive enzyme responsible for our normal digestion, absorption and assimilation of nutrients, the endocrine pancreas is to secrete islet peptide h- mones maintaining our glucose homeostasis. The pancreatic functions are nely regulated by neurocrine, endocrine, paracrine and/or intracrine mechanisms. Thus, dysregulation of these pathways should have signi cant impacts on our health and disease. Nevertheless, the underlying mechanisms by which pancreatic functions are regulated remain poorly understood. Recent basic science and clinical studies con rm myriad physiological and pathophysiological roles of the tissue renin-angiotensin systems (RAS). Of parti- lar interest is the recent identi cation of a local and functional RAS in the pancreas, which in uences both its exocrine and endocrine function. Its role in the pat- genesis of pancreatic diseases including diabetes and pancreatitis is increasingly recognized, as is the therapeutic potential of RAS antagonism: RAS blockade l- its disease progression of type 2 diabetes mellitus and impaired glucose tolerance, and may also protect against pancreatic in ammation.

Discover how to manage diabetes for a healthier and happier life! Written for anyone diagnosed with type 2 diabetes (and for anyone who loves someone with diabetes), Managing Type 2 Diabetes For Dummies is an essential guide to understanding the effects of diabetes and knowing what steps to take to successfully manage this chronic illness. Diabetes can lead to serious complications but people with diabetes can control the condition and lower the risk of its many complications. This is your easy-to-understand guide that shows you how. Under the direction of The American Diabetes Association, Managing Type 2 Diabetes For Dummies gives hope to the one in 11 people in the United States who are affected by the disease. Written in simple-to-understand terms, Managing Type 2 Diabetes For Dummies is filled with a wealth of expert advice and includes the most current information on recent medical advances for treatment. Improperly managed diabetes and consistently high blood glucose levels can lead to serious diseases affecting the heart and blood vessels, eyes, kidneys, nerves, and teeth. With the authorities at the American Diabetes Association on your side, you will have a practical handbook for preventing complications and managing diabetes with confidence! Prevent and manage the complications of the disease Combat diabetes-related anxiety and depression Lead a healthy life with type 2 diabetes Tap into the better living "rules of the road" with Managing Type 2 Diabetes For Dummies. By modifying your diet, consulting with your doctors, staying active, and understanding what medications are right for you, you will be on the path to a happier and healthier lifestyle.

Endocrinology, as a discipline, was a late arrival in the corpus of established subjects. Its growth in recent years has been prodigious, extending from mor phology to molecular levels. Most of the major endocrine glands were noted by the early anatomists, although the adrenal glands were not described until 1563 by Bartholomaeus Eustachius (1520-1574). On the other hand, elucidation of the function of these glands was extremely slow. Key work by A. A. Berthold (1849), although overlooked at the time, showed that comb atrophy in castrated fowl was prevented by testis transplantation. The idea that glands produced substances reach ing the bloodstream directly and not via excretory ducts stemmed from Claude Bernard, who first used the term internal secretion in 1855. The clinical observa tions of Thomas Addison at Guy's Hospital-published as a monograph in 1855 entitled The Constitutional and Local Effects of Disease of the Suprarenal Capsules -were seminal. However, the stimulus of this early research did not bring imme diate widespread further investigations. Upon the discovery of secretin in 1902, Bayliss and Starling considered the term "internal secretion" to be clumsy, and the term "hormone" was coined (from OQ UW-1 excite or arouse) and it was first used by Starling in his Croonian of 1905."

THIS BOOK collects together papers given at a NATO Advanced Research Workshop held at Il Ciocco (Lucca), Italy, from the 9th to the 15th April, 1989. It sets out to present the current state of understanding of the principles governing the way fluxes and concentrations are maintained and controlled in metabolic systems. Although this is a topic that has held the interest of biochemists for many years, it is only quite recently that the methods of analysing the kinetics of multi-enzyme pathways developed over the past two decades have come to be widely discussed or applied experimentally. Many biochemists remain sceptical that the new methods offer a real advance (except in complexity) over the landmark discoveries of the 1950s and 1960s relating to inhibition of enzymes at branch-points by the end products of metabolic pathways, and the interpretation of allosteric effects and cooperativity. Even those who have become convinced that the classical ideas provide only the starting point for understanding metabolic control have been by no means unanimous in their assess ment of the direction in which one should advance. In this book we have tried to include all of the current points of view, including the view that the classical theories tell us all that we need to know. We have not seen it as our role as editors to paper over the cracks that exist and to pretend that we can speak to the world with one voice."

The pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) has attracted the interest of our group during the last three decades. As early as 1969, a Nobel Symposium dealing with this topic was organized in Stockholm. This was followed in 1987 by a Nobel Conference devoted to the same subject. The main purpose of these meetings was to bring together the most distinguished scientists from all over the world and present theories on molecular and genetic mechanisms responsible for the development of glucose intolerance in NIDDM. This idea was followed also in the present symposium, "New Concepts in the Pathogenesis of NIDDM," organized with diabetologists from Toronto in Canada. Our purpose is to biannually organize international meetings covering important aspects of dia betes research, hoping that this type of interaction may result in new concepts and treat ment alternatives. For us, participating in this symposium in September 1992, the meeting in Stockholm was very stimulating and innovative. It is a special pleasure that almost all invited lecturers submitted manuscripts. Thus, the publication of the proceedings of the symposium makes it possible for all interested in diabetes research to share new ideas and findings presented at the meeting. Claes-G6ran Ostenson Suad Efendic Mladen V ranic v CONTENTS REGULATION OF INSULIN SECRETION Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. -G. Ostenson, A. Khan, and S. Efendic Perturbation ofIslet Metabolism and Insulin Release in NIDDM. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 WJ. Malaisse 2 Regulation of Cytoplasmic Free Ca+ in Insulin-Secreting Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

The dramatic recent expansion in genomic information has motivated the development of new approaches to characterize gene expression and function. A critical issue for both basic and clinical endocrinologists is the physiological role of genes involved in regulating endocrine functions. Transgenic technologies allow the translation of genotypic information into specific phenotypes by using gene overexpression or loss of specific gene functions. Murine functional genomics is thus of central importance in modem biomedical endocrine research. Although mice are at present, the preferred mammalian species for genetic manipulations because of the availability of pluripotent embryonic. stem cells and inbred strains and the relatively low breeding and maintenance costs, transgenic rats have also been generated and used to study endocrine physiology. The two basic techniques used in the creation of transgenic animal models are integration of foreign DNA into a fertilized oocyte by random chromosomal insertion and homologous recombination in embryonic stem cells that are then introduced into zygotes. Transgenic mice and rats serve as sophisticted tools to probe protein function, as models of human disease, and as hosts for the testing of gene replacement and other therapies. Embryonic stem cell libraries for mouse gene deletion are being developed, which will make it possible to generate knockout mice rapidly and without the need to analyze gene structure, construct targeting vectors, and screen embryonic stem cell clones. A novel approach to transgenesis for the expression of DNA within adult differentiated neuroendocrine cells in vivo is using viral vectors.

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."