Key questions involved in the treatment of disseminated breast cancer are discussed in this well-presented overview. It is the result of an initiative taken by the Swiss Group for Clinical Cancer Research to reveal the most recent developments in experimental and clinical research. The topics discussed include: the comparison of in vitro cultures of epithelial cells with breast cancer cells, the effect of steroids and their antagonists, the involvement of suppressor genes in tumour progression, the modulation of transforming growth factors by estrogen, and prognostic factors such as cERB-2 and EGF-R in breast cancer.

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper- function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self- constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

Research on the hormonal control oflactation - the subject of this monograph - has long been the major interest of this laboratory. Studies were initiated in the mid 1930s by the late Professor S. 1. Folley, FRS, who directed the work with immense enthusiasm and devotion until his untimely death in 1970. This fruitful area of basic and applied research has, in recent years, attracted widespread attention; there have been many exciting events and developments with a dramatic increase in the number of publications. These events are diverse and include the identification, isolation and sequencing of human prolactin; the identification and isolation of placentallactogens in several ruminant species with recognition of their importance in mammary growth and differentiation; the introduction of highly sensitive bioassay, radioimmuno- and radioreceptor-assay techniques for mammotrophic hormones; the growing clinical appreciation of the immunological and nutritional importance of colostrum and milk to the newborn; the intensification of studies on normal mammogenesis to establish a sound basis for studies on mammary cancer; and the exploitation of the mammary gland, with its characteristic differentiation patterns and multiple synthetic abilities, as a valuable tissue for the investigation of basic mechanisms involved in the synthesis under hormonal control of enzymes and secretory proteins; and for the study of hormone - receptor interactions.

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."

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was. considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Univer sities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.

Progress in basic research has made it necessary to redetermine the possibility of classic endocrine therapy for the treatment of patients with breast cancer. Exemplary, close cooperation between biochemis try and animal and clinical research led to a truly interdisciplinary and international exchange of ideas and experience at a symposium held in autumn 1978 in Heidelberg. We owe our thanks to ICI-Pharma for the kind support of this sym posIUm. The participation of Charles Huggins in the meeting as honorary chairman signified to all participants the meaning of this joint endeavour. It was the same Charles Huggins who through experimental work laid the foundation stone for endocrine ther apy of prostate and breast cancer, and who applied his findings clinically. Thousands of patients owe to him relief from their suffering. He contributed greatly to the attempt to find and stabilize the endocrine therapy for breast cancer, for which we thank him sincerely. We hope that the following contributions will similarly serve the well-being of our patients."

This volume is the product of a symposium held on 14-16 February, 1985 in Ham- burg in honour of the 65th birthday of Prof. Hans-Joachim Schumann. Schumann was born on 28 December, 1919 in Stralsund. He studied medicine in Cologne, Greifswald and Rostock. The chair of pharmacology in Rostock was held at that time by Peter Holtz. It was he who first introduced Schumann to pharma- cology in 1944 and who was his Doktorvater (research supervisor). Mter the war, Schumann again worked with Holtz in Rostock and then in Frankfurt am Main. He received decisive stimuli during a research fellowship, in 1956, in Prof. J. H. Burn's department in Oxford, where he also worked with Prof. H. Blaschko. In 1964 he ac- cepted his present position as ordentlicher (full) Professor and Head of the Institute of Pharmacology and Toxicology of the then newly founded Medical Faculty of Es- sen. He has remained in Essen despite being offered the chair of pharmacology in G6ttingen in 1968. It is interesting to observe how in the main lines of his scientific work, which now spans 40 years, Schumann has followed the steps involved in autonomic neuro- transmission from transmitter release to transmitter-receptor interaction.

Following a low-carb, high-fat ketogenic diet helps you lose weight, feel great and enjoy better energy and mental clarity. More and more people are turning to this healthy and delicious way of eating, but with lots of information about macronutrients and ketosis, it can be hard to know where to begin. Keto Kitchen makes it easy, with simple, delicious and inspiring recipes that fit into your busy lifestyle. This fantastic collection of recipes has been created by talented chef and keto devotee Monya Kilian Palmer. From Brown-Butter Scrambled Eggs to Slow-cooked Lamb Shoulder with Roast Cherry Tomatoes, every recipe is packed with flavour and nutrients. There are even desserts, including a Dark Chocolate and Raspberry Tart and Lime Cheesecake. The dishes are rich, indulgent and tasty. This is not diet food as you know it. Monya Kilian Palmer is a chef and culinary consultant originally from Cape Town, South Africa. Since moving to the UK in 2012, she has worked for both Heston Blumenthal's Fat Duck Group and Le Cordon Bleu. She has been following the ketogenic lifestyle since mid-2018.

The manuscripts in this volume were contributed by the speakers invited to the Acromegaly Centennial Symposium held in San Francisco, California in July 1986. The meeting was organized to commemorate the description of acromegaly by the French physician Pierre Marie, in 1886. The members of the Scientific Committee spent many hours assisting us in ensuring an outstanding meeting. The support of Serono Symposia, USA in all phases of the planning and execution of the meeting was sincerely appreciated and was highly professional. Special recognition roust be extended to Professor Roger Guillemin of the Salk Institute, whosp interest in medical history led him to devote a great deal of time and personal expense in obtaining information about the life of Pierre Marie. Dr. GuilIemin's presentation on the life and times of Marie was an extraordinary overview of the cultural, social, and scientific backgrounds in which Marie came to describe the disease, acromegaly. Dr. Guillemin' s findings, which were presented at the main banquet in a splendid audiovisual presentation, were clearly the highlight of the meeting and will long be remembered by the attendees. We were also honored by the presence of Dr. Martine Pierre Marie Granier, the great-granddaughter of Pierre Harie. In her address at the banquet, Dr. Granier provided several delightful and intimate vignettes concerning Pierre Marie, using old family records and photographs. The Scientific Committee wishes to extend its gratitude to Dr. Granier for adding immeasurably to the historical atmosphere of the meeting.

A variety of new techniques that promise to revolutionize the clinical management of early pregnancy are fully detailed in this state-of-the-art book. Leading international researchers describe fast-moving topics such as embryo manipulation and the diagnosis of congenital abnormalities. The technology of assisted reproduction has made it possible to study living embryonic material for the first time, which has led to rapid advances in our understanding of the human embryo's early development. For example, study of the embryo in the test tube has pointed to early pregnancy loss as a possible cause of later infertility. Even more important, diagnostic tests using sophisticated techniques of molecular biology can be run on single cells before the embryo is replaced in the uterus. Another area of advance is the diagnosis of congenital abnormalities in the first and second trimesters of pregnancy. Great improvements have been made in the techniques of chorion villus biopsy and ultrasound imaging. A spectrum of simple biochemical tests performed on the mother's blood can greatly improve the detection of Down syndrome and other chromosome defects. Together with other developments in the fields of molecular biology and endocrinology, these new diagnostic techniques are the beginning of a new age in clinical human genetics and embryology.

Publication of this monograph acknowledges great strides made in research on the zona pellucida during the past decade or so. The body of work presented testifies to a resurgence of interest in the zona pellucida, prompted largely by a renewed appreciation of its unique properties and its important functions during early mam malian development. It is gratifying to realize that the zona pellucida has at last achieved a well-deserved attention. Whereas extracellular coats of nonmammalian eggs have been studied intensively for many years, the zona pellucida by comparison, has until now taken a back seat. Fortunately, the research presented here signals an end to this situ ation. Many of the difficulties inherent in working with relatively small amounts of material have been overcome, paving the way for application of a wider variety of experimental approaches to the zona pellucida by a larger community of investigators. Hopefully, this monograph will serve as a catalyst in this regard. As revealed in these pages, application of contemporary experi mental methodologies has had significant impact on both pure and applied research on the zona pellucida. For example, modem im munological approaches have been used to assess molecular fea tures of zona pellucida structure and function, as well as to evalu ate the zona pellucida as a potential contraceptive target antigen."

These four volumes comprising "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 1988. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Committee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US Foundation for Studies in Reproduction Inc., and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 LIST OF CONTRIBUTORS TO THE SERIES H. Bartermann A. Abbondante First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" D-2300 Kiel 1, FRG Rome, ltaly M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Hammersmith Hospital Pennsylvania State University DuCane Road PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

These four volumes comprlslng "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 19B8. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Committee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US Foundation for Studies in Reproduction Inc., and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 xiii LIST OF CONTRIBUTORS TO THE SERIES A. Abbondante H. Bartermann First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" 0-2300 Kiel 1, FRG Rome, ltaly M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Pennsylvania State University Hammersmith Hospital DuCane Road PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

The "Handbook on Parathyroid Diseases" presents a comprehensive and concise overview of our current knowledge in the area of parathyroid function, hormone regulation and disease states.

The Handbook educates the reader using a case-based approach presenting current evidence in the field. The material is presented in an easy to read and understandable language and uses a plethora of tables and text boxes where possible. Complex concepts are conveyed in simple and clear language. Leading international experts contribute to this state of the art book providing a true depth of knowledge and practicality.

The mechanisms by which animals regulate the volume and composition of their body fluids has long had a particular fascination for students of biology. As a consequence, the subject can lay claim to an impressive record of ground breaking scientific achievements as well as a provocative body of philosophical speculation concerning the role of the system in the origin and evolution of life. Indeed, the entire concept of homeostasis on which so much of o r current biologic thinking is based, derives from Claude Bernard's pioneering exploration of the forces that determine the composition of this 'internal sea'. Other seminal achievements credited to this area of inquiry include the first description of a genetically transmitted human disease (familial neurogenic diabetes insipidus); the first isolation sequencing and synthesis of a peptide hormone (vasopressin and oxytocin); the first demonstration of peptide hormone synthesis by way of a larger protein precursor; the first description of resistance to the biologic actions of a hormone (nephrogenic diabetes insipidus); and the conceptual realization of the unique counter-current mechanism that permits concentration of the urine. This record of far reaching and fundamental advances has been distinguished by many fruitful inter actions between clinical and basic science."

A little over 12 years ago I wrote a small volume entitled Infertility. It seemed to me at that time that significant advances in the field called for the publication of such a volume. The following is from the preface to that volume: During the past 15 years considerable progress has been made in the field of infertility diagnosis and management. It is perhaps a paradox that much of this increased knowledge has come about because of Western medicine's preoccupation with the search for a means to control reproduction. As a result, we have achieved new insights into the physiologic mechanisms involved in reproduction, and we have found better methods for measuring physiologic changes in reproductive health and disease. To these advances can be added improvements in the utilization of endoscopic and surgical techniques, in the diagnosis and treatment of infections and endometriosis, and in the treatment of hormonal disorders. During this period, too, through workshops and conferences and in journals and texts, these latest advances have been made available to physi cians, an outstanding example being the two volumes of Progress in Infer tility, edited by Drs. Jan Behrman and Robert Kistner. As necessary as these publications are, they do not offer an overall view of infertility diag nosis and management."

THE STATE oF HoRMONE AcTioN levels were induced in concert with ligand occupa tion of certain membrane receptors and this second AND MoLECULAR REGULATION messenger (cAMP) was postulated to initiate intra cellular phosphorylation of unknown targets. At Molecular Endocrinology and Regulation is a this point, the field ofPeptide Hormone Action also burgeoning field, having experienced a remarkable came into being. period of growth since the late 1960s. At that time, These fields developed together for much ofthe there was no field of Hormone Action. The prevail next decade. Hormone Action Conferences invari ing view of how hormones worked ranged from ably contained talks on both types of receptors and effects on membrane transport of nutrients and progress was rapid and in concert with the explo precursors for RNA and protein synthesis, to effects sion molecular biology. In the steroid field, on the translation of mRN A at the level of ribo progress was more rapid initially, but by the mid somes. Therewas, however, asmallcadreofvoices 1980s, the peptide field attained equal mechanistic that predicted a possible nuclear action on mRN A status and the source of specialized conferences of synthesis. The first such paper was presented at the national endocrine meetings in 1967 and dealt with its own. Steroid hormone action investigators concen hormonal stimulation of oviductal protein synthe tratedonfirst understanding the "pathway" of action sis. It was about this time that a small group of for their hormones."

Sex Hormone Replacement Therapy addresses important issues in contemporary endocrinology. Its major emphasis is on the consequences of the menopause and on androgen deficiency in the absence of overt disease of the hypothalamus and/or pituitary in men. The use of hormone therapy for the primary prevention of cardiovascular disease in post-menopausal women has become an area of major debate, and the pros and cons are examined in detail. Secondary prevention also remains controversial and is addressed in this volume. An issue of particular concern is the treatment of estrogen deficiency symptoms in women with the diagnosis of breast cancer. Whether older men with some androgen deficiency symptoms and equivocally low plasma testosterone concentrations should be treated with androgens is also a matter of great debate, as is the efficacy and safety of plant estrogens in the treatment of menopause-related complaints. Sex Hormone Replacement Therapy will be of interest to students and non-specialists, as well as a wide range of medical practitioners including endocrinologists, gynecologists, rheumatologists and cardiologists.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

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."

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

Neuroendocrine Perspectives, Volume 7, is part of an international book series designed to keep clinicians and researchers appraised of important trends and new data in basic and clinical neuroendocrinology. It focuses on four very rapidly evolving major topics: - the role of dopaminergic regulation of the intermediate pituitary lobe in elucidating intracellular signal transaction pathways and other regulatory mechanisms involved in transsynaptic regulation of peptide biosynthesis, post-translational processing, and hormone secretion; - the physiological and clinical implications of corticotropin releasing factor for such areas as diagnosing Cushing's syndrome, defining the hypothalamic and pituitary origins of secondary adrenal insufficiency, and distinguishing Cushing's syndrome from psychiatric states associated with hypercortisolism; - the large number of neurotrophic factors that affect CNS neurons and of neurite promoting factors that modulate neuronal performance, with emphasis on their mechanisms of action and their possible therapeutic applications to peripheral neuropathies and central diseases; - and the many factors that regulate changes in female reproductive cycles during middle age, with careful distinction between neuroendocrine and ovarian components and special attention to the possible cause-and-effect relationship within the cascade of events resulting in acyclicity and infertility.

This book brings together some of the results and ideas produced by a large number of people-colleagues and students with whom I am privileged to work in the laboratory at Rockefeller University. In terms of my personal history I see it as a confluence of creative forces persons from whom I have learned. I was instructed in neuroanatomy by Walle J. H. Nauta at M. I. T., and later in a course at Harvard Medical School under the direction of Richard Sidman. At Harvard Medical School, where M. I. T. graduate students were allowed to cross register, the superb neurophysiology course was under the guiding spirit of Stephen Kuffler. Later, I benefited greatly from participating in his summer course in electrophysiological techniques at Woods Hole. Eric Kandel and his colleagues have provided us with the most exciting contemporary approach to the conceptualization and study of cellular mechanisms for behavior. Here at Rockefeller, Carl Pfaffmann and Neal Miller have been leaders in every sense of the word. Not only did they provide me with opportunities to grow to scientific maturity; they also set an example of clear thinking about mechanisms for mammalian behavior patterns. I wrote this book to show how the systematic use of increasingly detailed electrophysiological, neuroanatomical, and neuroendocrine tech niques can explain the mechanism for a mammalian behavioral response. The behavior in question happens to be sensitive to steroid hormones and plays a central role in reproduction."

Every year there are new and exciting developments in assisted human reproduction, but how much do we really know about the underlying causes of infertility? This volume explores recent progress in the understanding of the genetics of spermatogenesis and male infertility. Topics include fundamental advances and current problems in the development and function of the testis, an outline of clinical findings in male infertility and an overview of the role of the Y chromosome in male fertility. Comprehensive critiques of posttranscriptional control during spermatogenesis, mammalian meiotic sterility, and comparative genetics of human spermatogenesis from the perspective of yeast, Drosophila and mice provide a global overview of the field.

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.