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.

The hallmark of insulin resistance is an obstacle to glucose uptake, resulting in hyperglycemia and hyperinsulinemia as well as type 2 diabetes mellitus. The prevalence of diabetes mellitus is rapidly increasing world-wide and is becoming an important health problem. In this book, the authors present current research in the study of insulin resistance including: the pathophysiological basis for antioxidant therapy of insulin resistance; new insight into the regulation of insulin resistance; burn injury and its association with insulin resistance and hyperglycemia which complicates clinical management; and lipoprotein lipase and its role in insulin resistance.

The selection of prolactin as the subject of the Midwest Con ference on Endocrinology was not only dictated by the recent ad vances in prolactin research but also by the long tradition in that particular area of Endocrinology in the laboratory of C.W. Turner at the University of Missouri. Therefore, it seems only appropri ate that these proceedings of the Tenth Midwest Conference on En docrinology are dedicated to the memory of this scientist, deceased in August 1975 before completion of this volume, whose pioneer in vestigations have contributed substantially to the advancement of our knowledge in many areas of Endocrinology and who played a major role in the early phases of prolactin research. This volume contains a review of the early studies in Turner's laboratory and the latest results obtained by some of the leading research workers in this area and should be a fitting memory to C.W. Turner. Some of the manuscripts printed here were prepared after the conference was held and include material of more recent origin. Much of the delay in publication was due to the length of time de voted to preparation of these manuscripts. To the other authors and participants, and to Plenum Press, we express our appreciation for their patience and cooperation. We also with to thank Mrs."

The International Foundation for Biochemical Endocrinology is incorporated as a nonprofit research and educational organization. It is dedicated to the dissemination of knowledge, cooperative research programs, and cultural interaction on an international basis. The Foundation is concerned with both basic research and practical applications of biological knowledge to the betterment of humanity. Among our interests are global resource management, human reproduction, hormonal regulation of normal and cancer cells, study of aging and degenerative diseases, brain peptides, peptide neurotransmitter compounds, mechanism of action of hormones, peptide hormone synthesis, and recombinant DNA techniques. This monograph is the ninth sponsored by the Foundation in the Biochemical Endocrinology series. The previous four have been: Hormonally Active Brain Peptides: Structure and Function (1982), K. W. McKerns and V. Pantie, eds.; Reproductive Processes and Contraception (1981), K. W. McKerns, ed.; Synthesis and Release of Adenohypophyseal Hormones (1980), M. Jutisz and K. W. McKerns, eds.; and Structure and Function of the Gonadotropins (1978), K. W. McKerns, ed. These have all been published by Plenum Press.

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.

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

We are especially grateful to Dr. Philip Corfman and his colleagues of the Population and Reproduction Grants Branch of NICHD for making this Conference possible. The format of this volume follows in general the order in which the papers were presented during the Conference. The Conference was divided into four sessions, each of which was presided over by a capable and distinguished scientist. Each of these chairmen, Drs. T. H. Hamilton, G. A. Puca, R. L. Vande Wiele and H. G. Williams-Ashman provided valuable discussion and for their services we are most appreciative. The Editors are indebted to Mr. Robert Colligan for his help in organizing and in redacting the manuscripts. A special commen dation is also extended to Ms. Mary Jane Fowler who cheerfully and efficiently typed this entire volume. Finally, we express thanks to the individual participants of the Conference for their cooperation and prompt submission of the manuscripts and to the Plenum Press for ensuring the rapid publica tion of this volume. Anthony R. Means, Ph.D. Bert W. O'Malley, M. D."

It is unclear, and really no longer relevant, whether the information explosion that we now contend with has been fostered by the growth of specialization and subspecialization in medicine, or vice versa. What is clear is that the two are mutually supportive and constitute what would be in endocrine parlance a short-loop positive feedback system. As a result, for most areas of medicine, even the subspecialist in that area has a problem in maintaining currency, the more general specialist has substan tial difficulty in doing so, and the generalist is tempted to abandon the effort altogether. Nevertheless, for all, both the internal pressures of conscience and self-esteem and the external pressures generated by peer review, recertifi cation, and subspecialty boards create the need for continuous self-educa tion. We are, therefore, in an era in which the means of dissemination of new information deserves as much creative attention as does its acquisition.

The past two decades have seen steady progress in our understanding of the pathogenesis of atherosclerosis. The role of low density lipoprotein (LOL) increase and of LOL receptor deficiency or malfunctions in familial hypercholesterolemia has been largely enlightened by the works of Brown and Goldstein. These authors postulated also that modification of LOL to a form recognized by the scavenger or acetyl-LOL receptor may be required for lipid loading of macrophage-derived foam cells in the lesions. A growing body of evidence suggests that oxidative modification of LOL could enhance its atherogenicity by its implication as a factor in the generation of foam cells. Thus, if the role of LOL in the pathogenesis of hypercholesterolemia was well established a great deal of information appears currently on new approaches such as the mechanisms leading to the accumulation of foam cells, the impact of LOL structural alterations, notably oxidation and the role of gene mutations of apolipoprotein Band/or LOL receptor The opening topic is devoted to these new avenues outlined in the field of hypercholesterolemia. The first part concerns the genetic aspects of atherosclerosis: mainly the genetics of apo 1 ipoprote ins , their transcriptional regulation, the amino acid mutations of the apo B gene and of the LOL receptor gene, the structural domains and the acylation sites of apoprotein B.

This book is divided into two main sections, and covers a broad range of issues important for health practitioners to be aware of when caring for people with co-morbid diabetes and depression. Section One of the book contains the overall ideas and the more recent developments in measuring psychological morbidity in people with diabetes. When attempting to identify people with depression or other psychological problems, it is important for practitioners to recognize the limitations of screening as well as its utility. Issues such as the basic principles regarding when and when not to screen, the cultural applicability of tools, different questionnaire formats and key concepts such as sensitivity and specificity of tools, and their positive and negative predictive value, will be considered. In particular there has been increased interest in the concept of diabetes-related distress and several tools have been developed to measure this. There are broad-based measures of distress such as the Problem Areas in Diabetes (PAID) scale, the Diabetes Adjustment Scale (DAS), The Diabetes Health Profile, The Fear of Hypoglycemia Scale, etc. There are also a range of generic quality of life tools which have been used effectively in people with diabetes; for example the Medical Outcomes Survey Short-Forms (SF36, SF12), the World Health Organisation Well-being questionnaire (WHO-5) and the EQ5-D. These tools are important because they measure aspects of psychological well-being that are specifically associated with the experience of having a long-term conditions and so have important implications for both self-care and health care practice. The potential overlap of symptoms of depression and symptoms of diabetes-related distress are considered in this section and the implications for practice discussed. Section Two covers the most commonly used tools that have been used to screen for depression. For each tool considered some information which is easily referred to by the readeris set out in a table which includes details of the authors, time of first use, country where it was first developed, some examples of the questions used, the languages it is available in, data on sensitivity/specificity. Each instrument will then be discussed in terms of its use in research as well as practice, and its applicability in different patient groups, different cultural settings and so on. Guidance on the practical use of each tool is included, and the most popular depression screening tools are focussed on.

In the words of Disraeli, "To be conscious that you are ignorant of the facts is a great step to knowledge. " For most of us, the conscious awareness of relative ignorance is an uncomfortable aspect of daily life. New data appear in such inexorable profusion that the necessity for continuous retooling has joined death and taxes as an inescapable component of our destinies. Perhaps it is this "consciousness of ignorance" that accounts for the success of the preceding volumes of this new series. The Year in Metabolism and The Year in Endocrinology series were introduced with the avowed intention of "providing an efficient and enjoyable bridge between those who are creating new knowledge at the bedside and the professional consciousness of those for whom such knowledge is ultimately intended. " That objective seems particularly appropriate at a time when the award of the 1977 Nobel Prize in Medicine or Physiology to Guillemin, Schally, and Yalow has served to emphasize the epoch-making advances that have characterized the recent course of endocrinology and me bolism. For the 1977 volume of The Year in Metabolism, the previous formula has been preserved. The same internationally recognized authorities again have contributed commentaries about the progress in their areas of expertise. They have been joined by Drs. Jack W. Coburn, David L. Hartenbower, and Charles R. Kleeman, who have provided a new section on Divalent Ion Metabolism.

There is a world-wide epidemic on obesity. This epidemic is driving the immense proportions of Type 2 diabetes across the globe. While there are numerous therapies for treating Type 2 diabetes, the most effective therapy is prevention. Prevention of Type 2 diabetes can be achieved properly by simultaneous prevention of obesity. Prediabetes, or metabolic syndrome, is the period between simple obesity and diabetes, and this critical period needs to be identified in a more consistent and systematic manner by clinicians worldwide. Clinical trials have indicated that diabetes prevention can be achieved by lifestyle changes and also by certain medications, though none are yet approved for use in prevention. On the other hand, there are funding agencies such as the NIH, CDC, and State Institutions that are interested in studying the prevention paradigms in different communities and ethnic minorities who are most prone to this epidemic. For these reasons, this title by renowned physician-scientist Derek LeRoith is both timely and vitally important for academic physicians, practitioners, allied health care providers, analysts, community activists, and all others interested in this increasing epidemic. This book provides a unique and comprehensive synthesis of the prevention and early diagnosis of Type 2 Diabetes, focusing on identifying risk factors and then moving into topics that address how to prevent their progression to full-blown diabetes. The difficult task of changing patients' behavior is given special emphasis. The chapters in this practical volume are written by a wide range of international experts, reflecting the editor's distinguished, internationally renowned career. The volume is organized in eight sections: an introduction to the overall issue of prevention, definitions of values based on ADA guidelines, pathophysiology, discussion of a range of interventional trials regarding prevention, and an overview of state-of-the-art clinical management approaches. Comprehensive and timely, Prevention of Type 2 Diabetes: From Science to Therapy is an essential reference for those treating and researching Type 2 Diabetes.

Part memoir, part sports adventure, "Not Dead Yet "tells the inspirational story of Phil Southerland's battle with Type 1 diabetes and how he overcame all odds to start his own bicycle racing team and twice win the Race Across America. Blindness, kidney failure and death were all predicted for Phil by age twenty-five. Today, not only is Phil alive and well but as the founder of Team Type 1, he and his team of championship cyclists--many of them diabetics--have become health and fitness role models for people the world over. Together, they have taken on some of the most challenging endurance events in the world. Leading the pack is a serious challenge for any athlete, but for Phil and his teammates, it presents two daily battles: one to stay in razor-sharp race-fit condition, the other, to stay alive.

"An engrossing book, a sports adventure story with a medical subplot and a roster of dynamic characters, the most dynamic of whom is Phil himself....A story of tigerish determination and the utter resolve to never give up, to win against all odds." --"Diabetes Health"

"A must read for all of us with type 1 diabetes and for our support team of family and friends as well."--Showbusiness legend and "New York Times "bestselling author Mary Tyler Moore

"An uplifting and incredibly true adventure of a young man who beats the odds. Phil Southerland is an inspiration to those who live and struggle with diabetes as well as any individual who faces seemingly insurmountable challenges."--Steve Edelman, MD, University of California-San Diego, Founder and Director of Taking Control of Your Diabetes

Most of us spend at least two-thirds of our lives either sitting or standing. It is somewhat surprising, therefore, to find not a single book devoted to disorders caused by derangements of the normal physiological adjustments to changes in posture. In fact, until very recently, medical students have not even been advised to measure the blood pressure and heart rate in the upright posture as part of the routine physical examination. Although Bradbury and Eggleston first described orthostatic hypotension as a consequence of autonomic insufficiency in 1925, interest in orthostatic disorders has been slow to develop in the subsequent years. It is well known that the change from recumbency to the standing posture stimulates neurological, endocrine, and cardiovascular adjustments that ensure maintenance of a normal circulation despite the effects of gravitational forces. The mechanisms of these physiological responses to orthostasis have been stud ied by many investigators. Some of the defects to which antigravitational com pensatory mechanisms are subject, such as postural hypotension resulting from autonomic failure, have been studied intensively and have become part of the general knowledge of most medical practitioners. Other orthostatic disorders such as various other postural abnormalities of blood pressure control, and orthostatic edema-have received far less attention and have been unable to compete with the more dramatic and life-threatening ailments of humankind for a place in our standard medical texts. These disorders often give rise to distressing symptoms and may lead to severe impairment of health.

The tenth meeting of the International Foundation for Biochemical Endocrinology was held in Geilo, Norway near the end of September, 1982. The subject matter of the conference and the monograph was on "Regulation of Target Cell Respon- siveness." The local organizing committee was Asbj rn Aakvaag and Vidar Hansson. The scientific sessions covered a wide range of hormone action and cell response, including: peptide hormones and target cell response, regulation of insulin responsiveness, intracellular modulation of peptide hormone response, gonado- tropins and target cell responses, hypothalamic hormone- effects and regulation, steroid receptors and cellular control, hormones and growth regulation, and hormones and gene regulation. The chairpersons for the sessions were L. Birnbauer - A. Aakvaag, S. Taylor - R. S. Horn, F. Labrie - F. Rommerts, A. R. Means - K. W. McKerns, P. F. Hall - V. Hansson K. Griffiths - K. M. Gautvik, E. J. Peck, Jr. - E. Haug, F. S. French - W. T. Schrader, and E. M. Ritzen - B. Jegou. In addition to the scientific sessions in Geilo we were all delighted to sample some of the cultural and artistic attractions of Oslo, and to travel by train from Oslo via Geilo to Bergen. The scenery and hospitality were magnifi- cant.

The tenth meeting of the International Foundation for Biochemical Endocrinology was held in Geilo, Norway near the end of September, 1982. The subject matter of the conference and the monograph was on "Regulation of Target Cell Respon- siveness." The local organizing committee was Asbjjllrn Aakvaag and Vidar Hansson. The scientific sessions covered a wide range of hormone action and cell response, including: peptide hormones and target cell response, regulation of insulin responsiveness, intracellular modulation of peptide hormone response, gonado- tropins and target cell responses, hypothalamic hormone- effects and regulation, steroid receptors and cellular control, hormones and growth regulation, and hormones and gene regulation. The chairpersons for the sessions were L. Birnbauer -A. Aakvaag, S. Taylor- R. S. Horn, F. Labrie- F. Rommerts, A. R. Means - K. W. McKerns, P. F. Hall - V. Hansson K. Griffiths - K. M. Gautvik, E. J. Peck, Jr. -E. Haug, F. S. French- W. T. Schrader, and E. M. Ritzen- B. Jegou. In addition to the scientific sessions in Geilo we were all delighted to sample some of the cultural and artistic attractions of Oslo, and to travel by train from Oslo via Geilo to Bergen. The scenery and hospitality were magnifi- cant.

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

The Fifth Annual Washington Spring Symposium on Health Sciences attracted over 400 scientists from 20 countries. It was held at the Lisner Auditorium of the George Washington University in Washington. D.C. The theme of the meeting was neural and endocrine peptides and receptors. The meeting emphasized basic and clinical research on neural and endocrine peptides and receptors. The six plenary sessions emphasized pituitary peptides, releasing factors, brain peptides, growth factors, peripheral peptides, and clinical applications. The chapters in this volume are derived from each of these six scientific sessions plus the poster and special sessions. The Abraham White Distinguished Scientist A ward was presented to Dr. Julius Axelrod for his numerous contributions to the field of neurochemistry. He presented the keynote address, which was entitled "The Regulation of the Release of ACTH." Dr. Axelrod discussed numerous factors, such as the peptides CRF, VIP, and somatostatin, that regulate hormone secretion from pituitary cells. The Distinguished Public Service Award was presented to Senator Lowell Weicker, Jr., in recognition of his leadership and outstanding achievements in the United States Senate and for his legislative support for biomedical research and education. In the symposium banquet address, Senator Weicker stressed the need for continued federal support of biomedical science research.

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

The areas of experimental and clinical psychopharmacology have continued to grow in terms of the numbers of studies appearing in the literature as well as the activity generated by other disciplines that has influenced the output of behavioral pharmacology research. Psychoactive drugs have been considered for their comparative effects upon selected behaviors or for their effect upon diverse behaviors. Behavioral circum stances certainly influence not only the metabolism and action of psycho tropic drugs behaviorally, but also the disposition of these agents and/ or their metabolites in regions of the central nervous system. There can hardly be a psychopharmacology without a neuropharmacology, and the latter would seem to depend upon a neurochemistry. There would appear to be variables that exert potent influences upon the disposition and action of psychotropic drugs, that also relate quite directly to their effects upon behavior; these include drug interactions, nutritional status, environmental effects such as temperature, photic and tactile stimulation, and stress, and the basal status upon which such drug treatment is superimposed. In this volume of Current Developments in Psychopharmacology, which will be the last to appear in this format, we have sought to focus upon a series of current topical reviews that highlight representative areas of experimental and clinical research activity in psychopharmacology. In the first chapter, Dr. Lagerspetz reviews a frequently neglected aspect of psychopharmacological research-the actions of psychoactive agents upon the nervous system and behavior of non-mammalian species."

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

Can the art of predictive medicine anticipate the development of diabetes? And if so, what can be done about it? How early is early enough to intervene effectively? With what therapeutic modality? Why? Big babies are not an infrequent occurrence in mothers with normal carbohydrate metabolism for another 10, 20, or even 30 years. The abnor- mality present during pregnancy is now accepted as what is inherited with the diabetic predisposition, or what can be recognized as the diabetic susceptibility. It occurs before hyperglycemia, during the phase of dy- namic resistance to diabetes, during the prediabetic period. Prediabetes means before diabetes, and was applied for the first time by Mara~on in Spain, to signify the stage before hyperglycemia. Foglia in Argentina used the term in 1944 for his pancreatectomized rats. We pub- lished the first paper on humans in 1951 (Camerini-Davalos, R.A., Landabure, P., and Serantes, N., Rev Med Cordoba 39: 187).

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

genic constructs. Five articles are devoted to this topic ranging from the B-cell function in transgenic animals to the various effects on diabetes complications. The section on NIDDM, comprising of 10 articles, deals both with new and existing models, their particular widely varying pathogenesis, genetic character- istics and complications. The animals reviewed include: spontaneously diabetic OLETF rats, Chinese hamsters, Goto-Kakizaki rats, db/db mice, rhesus monkeys, dogs and an article demonstrating the genetic link between the Zucker fa/fa and corpulent cp/cp obese interstrains. We wish to welcome the new members to our Editorial Board, Dr. Hubert Kolb from Dusseldorf, Dr. Alex Rabinovitch from Edmonton, Dr. Takayoshi Toyota from Sendai and Dr. Soroku Yagihashi from Hirosaki. At the same time we would like to thank Dr. Douglas L. Coleman from Bar Harbor and Dr. George Eisenbarth from Denver for their editorial contribution to the previous LAD Vol- umes who have retired from the Editorial Board. With great sadness we have to mention Dr. Otho Michaelis IV from Beltsville, MD who suddenly passed away this year. Otho, or Mike as he was called by friends, made a significant contribution in developing and metabolically defin- ing several strains of corpulent cp rats and was extremely helpful in the editor- ial work of the LAD series. His contribution will remain in a lasting memory of all researchers of animal diabetes.

The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap plied in neuronal tissue to the neurohypophysis.