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

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

The practice of clinical reproductive medicine has practice in the era of managed care and coordinat gradually moved from its initial 1980-90 hospital ing ancillary offsite medical personnel. base to its present (circa 2001) office site of oper The objective of this text is to assist in this ongo ation. With this transition have been improvements ing endeavor by presenting in a clear, concise man in efficiency of practice often in response to ner many of the topics relevant to contemporary increased pressure to provide the most patient sat office-based infertility practice. The initial half of isfaction. An added challenge of office-based prac this text addresses topics which focus upon general tice has been taking on many of the responsibili concepts of infertility evaluation and practice. The ties of what had been traditionally the hospital's latter half is a practical approach to the execution domain. Some of these new responsibilities have of specific office-based infertility procedures. We included the ordering of operative supplies and hope this book will assist all medical personnel who equipment, the establishment of quality control dedicate their clinical effort in achieving what is programs, construction and maintenance of special most coveted by our patients, the birth of a healthy laboratory spaces, redesigning efficient methods of newborn. DAVID B. SEIFER, M. D. UMDNJ-Robert Wood Johnson Medical School ROBERT L. COLLINS, M. D. The Reproductive Center, Youngstown, Ohio October 2001 vii Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi . . . . . . . . . . . . . . . . . 1 Evaluation of the Female for Infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bryan D."

The media now regularly feature breakthroughs on the influence of prenatal hormones on the brain and behavior, for instance the link to financial performance or risk management. Based on these findings and their own experiments, the authors present the Hormonal Quotient (HQ) as a scientific, holistic and reliable career management and personal development tool for professionals. Eight HQ profiles and their corresponding typical business skills and preferences are presented and enable the reader to benchmark their HQ with peers, design an ideal career plan, build a winning team in business and find the perfect work-life balance. A complimentary website allows readers to easily measure their HQ online.

By the author of "The Right Sensory Mix," Berry-AMA Book Prize Finalist 2011 - one of the four best marketing books in 2011 according to the American Marketing Association Foundation.

The Berry-AMA Book Prize is awarded annually be the American Marketing Association Foundation (AMAF) and recognizes books whose innovative ideas have had significant impact on marketing and related fields.

The sellar region and paranasal sinuses constitute the anatomical sections of the skull base in which pathological entities warrant interdisciplinary management. Processes originating in the paranasal sinuses can reach and involve the skull base in and around the sella, sometimes not respecting the natural dural boundary. On the other hand, lesions involving the sellar block, such as pituitary adenomas and meningiomas, can also extend downwards into the paranasal sinuses. The orbit and cavernous sinus may be subject to involvement and infiltration by both paranasal and sellar pathology. The advancement and new achievements of modern diagnostic procedures, such as high-resolution CT, three-dimensional reconstruc tion, MRI, and MRI angiography, as well as the detailed selective angiographic protocols and endovascular techniques, have increased the possibilities for surgical management of this type of pathology with extra- and intracranial involvement. Long-standing and intense inter disciplinary work has led to sophisticated operative approaches which for benign tumors allow total excision with preservation of structures and function, and for some malignant lesions permit an en bloc resec tion via a combined intracranial-extracranial approach. This volume reflects the work and scientific exchange which took place during the IV International Congress of the Skull Base Study Group, held in Hanover. Leading authorities in the basic sciences including anatomy joined with diagnosticians, clinicians, and surgeons from different fields to evaluate the state of the art of this topic in skull base surgery."

For many years, patients who complained of prostatism had only a few treatment choices. The patient was either a candidate for an elective prostatectomy, or the operation was deferred until the patient became more symptomatic. The present text summarizes the multiple options which have become available to the practicing urologist. Minimally invasive techniques such as transurethral incision of the prostate, balloon dilatation, hyperthermia, laser therapy, and prostatic stents are described. Medical treatment with alpha-blockers, 5 alpha-reductase inhibitors, and flutamide are addressed by authors who have had extensive clinical experience with the use of these agents.

Die Beitrage dieses Buches beschaftigen sich mit Autoimmunitat, Immuntherapie des Typ-I Diabetes, Virusgenese, Insulintherapie und -allergie. Schwerpunkte liegen auf den dynamischen Aspekten der Insulinsubstitution unter Berucksichtigung einer angepassten Diat und der Therapie mit oralen Antibiotika, Insulinen und Pro-Insulinen. Gleichzeitig wird anhand der Makro-Angiopathie und der Neuropathie auf die Auswirkungen der dynamischen Insulinsubstitution bei Sekundarkomplikationen hingewiesen. Die Moglichkeit der computerunterstutzten Therapiefuhrung und glukosesensorgesteuerten Biofeedback-Kontrolle werden vorgestellt. Ein umfangreiches Kapitel vermittelt den aktuellen Stand der experimentellen Forschung und der klinischen Anwendung der Pankreas- und Inselzelltransplantation.

Recent years have seen tremendous progress in the field of hormone action and consequent signal transduction. The 40th Colloquium Mosbach was devoted to the discussion of results concerning the molecular process of hormone action, especially the processes following hormone binding to the corresponding receptors. Structural and functional aspects of steroid hormone receptors as well as ion-channel-coupled and enzyme-linked receptors were treated in detail. Particular interest focussed on the latest results concerning transcriptional control, protein phosphorylation, the role of G-Proteins, oncogene proteins, involvement of phospholipases and the regulation of ion channels.

Diabetes mellitus represents one of the most frequent and serious clinical syn dromes in contemporary medicine. Since the end of the nineteenth century, the endocrine pancreas has been implicated in the pathogenesis of this disease. Several pathologists of the twentieth century detected various lesions and mor phologic alterations in the pancreatic islets of diabetic patients, but the patho physiologic basis of their findings remained long obscure. The systematic mi croscopic work of WILLY GEPTS clarified the views and related the variety in histopathology to differences in origin, duration and clinical expression of the disease. Over the past two decades, the concept of a multifactorial origin of diabetes has become widely accepted. Various agents and mechanisms have been identified which can lead to a quantitative or qualitative deficit in pancre atic B-cells. The purpose of this book is to bring an update on the many path ways which may induce an absolute or relative insufficiency in insulin release and hence a diabetic state. Rather than bringing a complete account on all re search relevant to the understanding of the pathology of the diabetic pancreas, the authors of the various chapters of this volume have focussed on selected processes which can impair B-cell function, survival or regeneration.

As I reflect on the evolution of this book, I am struck by the differences be tween my early conceptions and the final product. When I was first ap proached by Springer-Verlag regarding a monograph on my interests in the area of fetal lung development, I imagined that it would be relatively easy to summarize my contributions, plus the work of other investigators as needed for proper perspective. This rather naive idea was abandoned as I prepared my initial outlines for the monograph. I quickly realized that con tributions from my laboratory are not sufficient for telling the story of "hormones and lung maturation." The result of this decision is a longer and more heavily-referenced book than I originally envisioned. Although I have attempted to discuss in considerable detail most aspects of hormones and the fetal lung, I know with certainty that I have not in cluded all relevant references in each area. In most of these instances this reflects my impatience or lack of diligence, and I offer my apologies to those investigators whose work has been so omitted. In some situations published work has not been cited in a deliberate decision to limit the breadth of discussion or, rarely, due to my judgment of major shortcom ings in experimental design or execution."

It has been my privilege and pleasure during the past half century to participate in the unfolding of present-day concepts of the mammalian female reproductive cycles. When the studies recorded here began in the late 1930s it was already established that cyclic ovarian function is governed by gonadotropic secretions from the anterior pituitary gland, the "conductor of the endrocrine orchestra," and that in turn this activity is importantly dependent in some way upon secretion of estro gens and progesterone by the ovaries. Although a role of the nervous system was recognized for the reflex-like induction of ovulation in rabbits and cats and the in duction of pseudopregnancy in rats and mice, and although there was even some evidence of neural participation in ovulation in rats, a major central neural role in the female cycle of most species was not apparent. Gonadotropic fractions of pitui tary extracts having distinct follicle-stimulating and luteinizing activities in test ani mals had been obtained, and these respective effects had been fairly well charac terized. Prolactin was well known for its lactogenic activity, but its luteotropic role in rats and mice had yet to be revealed. The molecular structure of the several estro gens and progesterone was known, and they were readily available as synthetic pro ducts. The broad concept of ovarian-pituitary reciprocity appeared to be an accept able explanation of the female cycle, with the ovary in control through the rhythmic rise and fall in secretion of follicular estrogen.

The term polycystic ovary syndrome (peOS) is meant to describe a clinical endocrinopathy characterized by menstrual irregularity and evidence of hyperandrogenism. While recognized since the 1800s, a clinical composite was not constructed until 1935 when Stein and Leventhal reported their findings of seven women with infertility, menstrual dysfunction, hirsutism, and enlarged ovaries. Notably, the ovaries contained numerous multiple cysts and the ovarian capsule was thickened. At the time, this preciseness of definition was sufficient to entitle the entity Stein-Leventhal syndrome. Subsequently, over the intervening years as investigators attempted to un ravel the pathophysiology and genesis of this disorder and the number of reported studies increased, there ensued a gradual and distinct terminologic conversion to polycystic ovary syndrome, which, whether intentional or not, connoted a less well-defined condition. Perhaps this is appropriately so, given the seemingly broadening spectrum of clinical presentations and the continuing debate over what constitutes peos. The expansive new knowledge about peos was discussed to a significant degree at an international symposium organized by Serono Symposia USA and held in Boston in the late spring of 1995. Ovarian physiology, including the fate of the follicular unit, was a central focus with several presentations on the genesis, growth, and death of ovarian cellular components. A discus sion of the regulation of ovarian cell function was also highlighted and comprised a major portion of the program."

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 epididymis has great significance in the reproductive biology of the male and it is gaining recognition as an organ worthy of study in its own right - where the secretory and absorptive activities of one tissue (the epithelium) profoundly modify the function of another (the spermatozoon). Apart from cases of epididymal agenesis or physical blockage, however, it is not yet known to what extent mal functions of the epididymis contribute to "unexplained" male infer tility, but its importance as a target for antifertility agents in the male is now widely appreciated. This monograph evolved from two lectures on epididymal func tion given at the National Research Institute for Family Planning, Beijing and the Sichuan Provincial Family Planning Research Insti tute, Chengdu, China in 1983. In order to stress for this audience the central importance of the epididymis in fertilisation, and so highlight its potential for attack by antifertility agents, the talks attempted to put the epididymis in reproductive perspective by stressing the func tional development of the sperm cells during their sojourn in the epididymis, rather than merely listing the changes observed in them."

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.

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."

It is well established that progesterone plays a role in the brain and hypophysis as a facilitator and inhibitor of sexual behavior and gonadotropin release in the female rat (Everett 1961; Caligaris et al. 1971; Brown-Grant and Naftolin 1972; Dorner 1972; Meyerson 1972; Barraclough 1973; Goldman and Zarrow 1973; Mann and Barraclough 1973; Freeman et al. 1976; Feder and Marrone 1977; Goodman 1978; Attardi 1981), guinea pig (Morin and Feder 1974), and primates (Odell and Swerdloff 1968; Spies and Niswender 1972; Yamaji et al. 1972; Karsch et al. 1973; Dierschke et al. 1973; Knobi11974; Clifton et al. 1975). In an attempt to learn whether a specific progesterone uptake mechanism exists in the brain and the hypophysis, the distribution and retention pattern of radioactivity after in vivo injection of labeled progesterone was studied. Early work of Kato (1963) did not show a selective uptake of radioactivity in the hypo- thalamus of immature and estrogen-primed immature rats after injection oflow- specific-activity [14C]progesterone, but some tendency of the reticular formation to take up radiation was observed. Laumas and Farooq (1966) reported that after intravenous administration of labeled progesterone to ovariectomized estrogen- treated rats, radioactivity in the brain and pituitary appeared to show a very slight, insignificant increase 1-2 min after injection, but the uptake pattern was not definite, as had been seen with estradiol. Seiki et al.

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."

In the last decade, it has become increasingly evident that the clini- cal and morphologic changes underlying many of the complications of diabetes, including cataract formation, retinopathy, nephropathy, neuropathy, and macrovascular disease, are preceded by a variety of disturbances of biochemical and physiologic origin. Dr. Cohen has recently written a superb monograph, entitled Diabetes and Protein Glycosylation: Measurement and Biologic Relevance, in which she thoroughly explores how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for main- tenance of long-term euglycemia. In the present volume, The Polyol Paradigm and Complications of Diabetes, she reviews, in a most succinct and thorough manner, how another biochemical mechan- ism, involving the polyol pathway, is involved in the pathogenesis of such diabetes complications as retinopathy, neuropathy, nephropa- thy, and cataract formation. Dr. Cohen gives us a clearly written and comprehensive mono- graph, reviewing the chemistry of the polyol pathway and of the aldose reductase inhibitors, and the pathophysiologic significance of increased polyol pathway activity in a variety of tissues affected by Vlll Foreword diabetes mellitus. She insightfully describes the relationship of increased polyol pathway activity to altered metabolism of inositol- containing phospholipids and to changes in various tissue concentra- tions of myo-inositol. Finally, she provides us with a careful review of the existing experimental and clinical studies with a variety of different aldose reductase inhibitors that have been and are being performed in the hope of preventing or reversing long-term compli- cations of diabetes.

This book is an edited collection of the literature on leptin beginning with the discovery of leptin and a study of its affect on animals and in humans. Chapters will focus on the discovery, history, roles and regulation of leptin in all the major areas of physiology, as well as on assay methods, phylogeny and genetics. The timing of this volume is long overdue and is the first comprehensive coverage of leptin physiology in the field.

- This series is indexed in index Medicus

- The turn around time for this series is fast, making the research as accurate as a journal

Biomedical devices that contact with blood or tissue represent a wide range of products. Depending on their potential harm to a body, medical devices are categorized according to the degree, so their safety can be assured. All biomaterials are by definition designed to contact with a body for a certain period of time. The nature of the body contact, as well as the duration a material contacts with the body may initiate unwanted biological In comparison with invasive devices Oike catheters and medical responses. implants contact directly with tissue or with the circulating blood) non invasive devices (like wound-dressings and contact lenses contact with the skin, the sclera, and the mucosa or with open wounds) have a lesser risk of hurting a patient. When blood contacts with a foreign material, plasma proteins become absorpted to the surface within a few seconds. The reactions that follow, the so-called intrinsic pathway lead to the formation of fibrin and activation of platelets and white blood cells, result in blood clot formation."