The treatment of menopausal and postmenopausal symptoms is a focus of considerable debate, on account of both the medical and social factors involved. And perhaps the cause of the greatest current interest and concern is not so much the effectiveness of present-day treatment but its safety. Opinions on the subject vary; and to resolve the arguments we must turn to the results of scientific experiment, both the clinical and biological. It is only by comparing experimental results that it is possible to move forward, albeit slowly, towards a generally agreed consensus based upon objective scientific data. It is for this reason that we are particularly grateful to Ayerst Laboratories whose support and help have enabled us to turn our original proposal for an International Symposium into a reality. We are also grateful to the publishers for the efficiency with which they have organized the publication of the Proceedings. It is our hope and that of all the distinguished participants that all readers of this volume will be able to find something in it which will stimulate further thought and discussion - even though they may not necessarily agree with all the conclusions expressed - for the success of a Symposium turns not only on the subject under examination but also on the quality of debate and discussion it encourages.

This volume contains papers presented at the Conference on the Demographic and Programmatic Consequences of Contraceptive In novations, which was sponsored by the Committee on Population and held at the National Academy of Sciences, October 6-7, 1988. The papers consider how new contraceptive methods currently being developed and changes in the use of already available contraceptives could affect contraceptive practice, levels and patterns of abortion use, and the health of women. In addition, several of the papers re view the probable consequences of introducing new technology into family planning programs in developing countries. The Committee on Population sponsored this conference in order to stimulate think ing and to provide a forum for scientists, family planning program managers, and donor agency personnel to exchange information and ideas about these important issues. The committee is publishing these papers to expand the discussion of consequences of contracep tive innovations and to give scientists, policy makers, and members of the public who could not attend the conference an opportunity to learn about new developments in fertility control and their likely consequences for individuals and the societies in which they live. NEED FOR NEW METHODS While a strong case can be made that the pill and the intrauterine device (IUD) have contributed to declines in the level of unintended pregnancies around the world, it is also clear that for many couples existing methods present problems.

About 21 years ago prenatal diagnosis became part of the physician's diagnostic armamentarium against genetic defects. My first monograph in 1973 (The Prenatal Diagnosis of Hereditary Disorders) critically assessed early progress and enunciated basic principles in the systematic approach to prenatal genetic diagnosis. Six years later and under the current title, a subsequent volume provided the first major reference source on this subject. The present second (effectively third) edition, which was urged in view of the excellent reception of the two earlier volumes, reflects the remarkable growth of this new discipline and points to significant and exciting future developments. Notwithstanding these advances, the use of the new tools and techniques for the benefit of at-risk parents has taken many more years than most anticipated. Key factors have been the lack of teaching of human genetics in medical schools in the preceding decades and the difficulty of educating practicing physicians in a new scientific disci pline. Even today the teaching of genetics in medical schools leaves much to be desired and this will further delay the introduction of newer genetic advances to the bedside."

Interest in sexuality and reproductive function does not cease when people begin to age. Instead, a new set of questions arises. Women want to know if it is safe to have babies in their late thirties and early forties. They want to know more about hot flashes and other symptoms of menopause-which ones are dangerous and which are merely uncomfortable. They are eager to learn about the relative risks and benefits of estrogen replacement therapy. Men, too, are concerned about age-related changes in their sexual function. Experts in reproductive physiology, gerontology, and genetics met at the National Institutes of Health in June of 1984 to discuss these and other concerns about aging and the reproductive system. The conference on Aging, Reproduc tion, and the Climacteric was sponsored by the American Fertility Society, The National Institute on Aging, and the National Institute of Child Health and Human Development. This volume is based on the proceedings of that confer ence."

The 15th International Symposium of the Japan Human Cell Society on Cell and Molecular Biology of Endometrial Carcinoma brought together leading researchers from Japan and around the world. The papers collected here are the work of twenty-two leaders in their field and are organized in ten major categories. The first section, in vitro experimental systems, takes up the pioneering work by Kuramoto in 1968 and Nishida in 1980 in establishing, respectively, the HEC-1 and hormone-responsive endometrial carcinoma cell lines. Other topics include apoptosis, proliferation, and growth factors; cell cycle regulators; signaling pathways; angiogenesis; carcinogenesis; hormones and hormone receptors; genes and gene expression; endometrial receptivity; and chemo-resistance and -sensitivity. Presenting the latest work in the cell and molecular biology of endometrial carcinoma, this volume is a valuable resource for gynecologists, pathologists, and molecular biologists.

The no-man's-land between reproductive physiology and immunology is becoming crowded. The last 10 years have seen a revolution in our under standing of many reproductive processes, brought about by the application of ever more sophisticated immunological methods. The increasing precision of these techniques has given us specific ways of assaying, enhancing or blocking hormonal mechanisms to yield more critical and interpretable information. In this volume eleven authors have presented the current status and future prospects of some immunological aspects of reproduction and fertility con trol. These include the relationships between mother and fetus, the diagnosis of pregnancy, the immunological complications seen in clinical management of human reproduction and some novel approaches for immunological control of fertility. We hope that in these chapters we have achieved an up-to-date account of a fast-moving field that calls on several disciplines. We intend the book to provide an adequate background and a current review for research workers and clinicians who wish both to understand the complex mechanisms involved and to develop improved scientific and clinical methods. We hope too that the student and newcomer will find this a useful reference book."

Years of involvement, firsthand experience and research at the Menopause Clinic of the Groote Schuur Hospital, Cape Town, exist as the background to this book. The Clinic itself, however, as one of the first in the world to be established, if not the first, has a story and a lesson of its own to offer, and is therefore deserving of a brief description as the preface to the book. In 1967, shortly after Christiaan Barnard had completed the historical first human heart transplant at the Groote Schuur Hospital, I happened to be in West Berlin and was invited to visit a major international pharmaceutical firm. A new female hormone was mentioned, and thereby started my interest in the subject. Upon my return to Cape Town, I spent many hours in the large medical school library and completely surveyed the menopause literature to 1967. I was stunned by its general inadequacy and was bitten by a challenge to clarify what menopause really was, and to define the proper place of hormone replacement therapy.

Discrimination of self from nonself is the major function of the immune system and understanding the mechanism(s) involved a main employer of immunologists. Hence, the age-old puzzle of why a fetus that contains a panel of major histocompatibility (MHC) antigens derived from its mother and its father is not rejected (spontaneously aborted) by lymphocytes from its mother who should theoretically recognize foreign MHC molecules from the father has remained of great interest. This dilemma has enticed immunologists and developmental biologists for many years. This volume was created to present the information currently on hand in this subject to the scientific public. The guest editor, Professor Lars Olding, has a long and distinguished history of contributions in this field, having been one of the main propo nents of the argument that lymphocytes from the fetus play an active role in this process by suppressing lymphocytes from the mother from proliferating and thereby acting as killer cells. His work has defined the phenomenon and identified suppressor molecules (factors) involved in the process. In a different but related chapter, Margareta Unander extends such observations to the clinical study of women with repeated "habitual" mIS carriages."

Surgical Diseases in Pregnancy explores the special problems confronted by the gynecologic surgeon treating pregnant patients. These problems include acute appendicitis, inflammatory bowel disease, breast cancer, carcinoma of the cervix, ovarian tumors, renal stones, and incompetent cervical os. Other topics discussed are induced abortion; septic abortion and septic thrombophlebitis; ectopic pregnancy; surgical disease of the endocrine glands during pregnancy; gastroduodenal, hepato-biliary and pancreatic emergencies during pregnancy; pregnancy in the kidney transplant recipient; and pregnancy and cardiac prosthetic valves.

It is clear today that several prostaglandins play an important role in the regulation of many of the physiological events of the reproductive organs in the human. Both naturally occurring prostaglandins and their analogues are used routinely in many countries to ripen the cervix and induce labour at term as well as to dilate the cervix and to terminate pregnancy. Prostaglandin biosynthesis inhibitors are widely used in the treatment of primary dysmenorrhoea. The editors have aimed at an accurate, thorough, yet easily under standable review of the status in 1986 of medical knowledge regarding both the physiological importance and the clinical use of prostaglan dins and their inhibitors in obstetrics and gynaecology. I believe this book will be of value for all clinicians concerned with reproductive health. The list of authors guarantees an authoritative and up-to-date review of this active field. SUNE BERGSTROM Karolinska Institutet, Stockholm, Sweden Table Examples of clinical use of natural prostaglandins and some prostaglandin analogues Indications Prostaglandin Route of administration Manufacturer Dilatation of the cervix prior 15-methyl-PGF * Intramuscular Upjohn, USA 2 to vacuum aspiration 16-phenoxy-PGE methyl sulphonylamide Intramuscular Schering AG, West Germany 2 16,16-dimethyl-PGE methyl ester 1 Vaginal ONO, Japan; May & Baker, UK Second trimester abortion Intra -amniotic Upjohn, USA; ONO, Japan PGF 20 Upjohn, USA PGE Vaginal 2 Upjohn, USA 15-methyl-PGF 2.

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

In this book we have expert urologists and gynaecologists on the two sides of the Atlantic working together with a common interest, the inadequate female urethra. What makes this volume so valuable is that it is not restricted to one speciality or one cult, but bravely (and systematically) presents established principles and practice. Not only is the current knowledge of the anatomy and function of the continence mech anisms defined by experts carefully selected by the two authorities in the field, but this infor mation is directly applied to clinical problems for the reader to use in the care of patients. Because the basics are presented first, and followed by the methods of diagnosis, the sec tions describing each form of treatment, whether medical or surgical, are set on rational bases. These are not cookbook directions. This background is especially valuable because the incontinent female usually has a complicated disorder, each case being different, so that the responsible gynaecologists or urologists must apply as much understanding as technique if their efforts are to achieve dryness. The clear descriptions and illustrations in this book, then, act as guides as much as directives. This second edition builds on the success of the first. All of us trying to help these unfortu nate women will do more for them from having this new edition at hand."

Numerous reports demonstrate that the reproductive system could be affected by multiple potential toxicological agents. The volume includes different aspects of the development of new approaches to in vitro testing using sperm cells and systems involved on reproduction in mammals. Comparative analysis of in vivo and in vitro methods has been included to take steps towards the further development of and applications of new systems for germline toxicology.

Endometriosis is one of the most common diseases of women. This book provides a practical, clinical and thorough examination of both the medical and surgical treatment of this disease. A world renowned group of contributors address basic issues, management approaches and selected special topics, emphasizing the latest advanced operative techniques.
Topics include: - minimally invasive and advanced laparoscopic surgical technique in the treatment of endometriosis - treatment of endometriosis of the ovaries, cul-de-sac, gastrointestinal and urinary tracts, and extragenital sites - management of recurrent endometriosis - treatment of infertility and pelvic pain associated with endometriosis - guidelines for medical management and combined medical-surgical management.

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.

Cytologic diagnosis of cancer has its roots in clinical micro scopy as it was shaped during the first half of the 19th century. In reviewing some of the early writing on this subject, one is amazed at the accuracy of the descriptions and soundness of the observations. Cytology of the urine is no exception: in 1864 Sanders described fragments of cancerous tissue in the urine of a patient with bladder cancer (Edinburgh Med. J. 111, 273). This observation was confirmed by Dickinson in 1869 (Tr. Path. Soc. London, 20, 233). It is a source of special pride to me that in 1892 a New York pathologist, Frank Ferguson, advocated the examination of the urinary sediment as a best means of diagnosing bladder cancer, short of cystoscopy. Papanico laou freely acknowledged these contributions while estab lishing sound scientific bases for continuation and spread of this work. Papanicolaou's work in the area of the urinary tract has not fallen on dead ears. He documented to several urologists who were within his sphere of personal influence, mainly Dr. Victor Marshall, Professor of Urology at Cor nell University Medical School, that urinary tract cytology was a reliable tool in the diagnosis of urothelial carcinoma. Some of us who have attempted to spread the master's word had their share of success within institutions with which we were associated.

Several papers dealing with the clinical relevance of steroid hormone receptors in breast cancer have already been published. However, no publication has overviewed studies currently being conducted in Europe, nor is there a register of the european centers performing receptor assays. It has been our purpose to fill these gaps. A large majority of authors who we contacted kindly agreed to con tribute to our book. Papers were grouped into six main parts according to their contents. The abundance of clinical data relevant to receptor assays led us to add critical summaries to help the reader to form his own opinions on the subject. We would like to thank Drs. R. J. B. King, G. Contesso, L. Santi, and E. Engelsman, who helped us in this regard. We hope that this book will enable the reader to become acquainted with the present state of European steroid hormone receptor studies devoted to breast cancer treatment. We also hope that it will promote cooperation between European oncologists involved in this field of research."

Pathobiology of Human Germ Cell Neoplasia is a state-of-the-art compendium on a very recent branch of tumor biology. It offers an awareness and understanding of germ cell tumors: from the earliest stages to their va- rious differentiations. Original data for this volume was supplied by experts in the fields of pathology, developmental biology, genetics, molecular biology and other related fields. This compilation of knowledge provides information necessary to persons working in clinical and preclinical areas.

Retinal haemorrhage occurring during birth is a common feature in the newborn. There is no basic funduscopic or morphologic difference between this perinatal type of haemorrhage and that in the adult. The difference is that perinatal haemorrhage resorbs rapidly, within a few days, and no functional defects of retinal vessels are known. The fIrst observation of perinatal haemorrhage took place nearly 100 years ago. Many observations have been published in short papers; what was still lacking was a systematic pathogenic classifIcation of the different types of haemorrhage, a compari son of the perinatal type of other types of retinal haemorrhage, a comparison to other perinatal ocular haemorrhages, a detailed histologic description and a multi-faceted correlation of haemorrhage to aetiologic factors. The author has based his comprehensive evaluation on the observation of more than 400 newborn infants, the reexamination of several cases with macular haemor rhage, the histologic work-up of serial sections and the review of extensive literature. It is a remarkable fact that a physiologic process, birth, is related to this type of vessel rupture, which is present during a short period of postnatal life. In its complex analysis of these facts and conditions this book is particularly valuable."

Having received the invitation from Springer-Verlag to produce a volume on drug-induced birth defects for the Handbook of Experimental Pharmacology, we asked ourselves what new approach could we offer that would capture the state of the science and bring a new synthesis of the information on this topic to the world's literature. We chose a three-pronged approach, centered around those particular drugs for which we have a relatively well established basis for understanding how they exert their unwanted effects on the human embryo. We then supplemented this information with a series of reviews of critical biological processes involved in the established normal developmental patterns, with emphasis on what happens to the embryo when the processes are perturbed by experimental means. Knowing that the search for mechanisms in teratology has often been inhibited by the lack of understanding of how normal development proceeds, we also included chapters describing the amazing new discoveries related to the molecular control of normal morphogenesis for several organ systems in the hope that the experimental toxicologists and molecular biologists will begin to better appreciate each others questions and progress. Several times during the last two years of developing outlines, issuing invitations, reviewing chapters, and cajoling belated contributors, we have wondered whether we made the correct decision to undertake this effort.

The advent of assisted conception procedures such as in-vitro fertili sation (IVF) has provided the impetus for exploration of the factors that lead to the establishment of pregnancy. This collection of papers from leading research workers brings together current concepts of the processes which may be of importance in implantation. The complex signals from the embryo to the ovary, endometrium and myometrium are now being revealed through studies in both primates and other mammalian species. This book addresses the interrelationship of pituitary and ovarian hormones in controlling ovulation and the preparation of the intrauterine environment for implantation. Once fertilisation has occurred and trophoblast has formed, the next vital step is the production of materials which signal the presence of the pregnancy to the rest of the body. Trophoblastic proteins and other early-pregnancy factors are prime candidates for this role. Recent studies have emphasised the importance of the intrauterine environment in implantation. Specific secretory products of the endometrium have great potential in this process. The prostaglandins also play an essential part. Immunological adjustments are now considered a condition for the successful establishment of pregnancy. The possible use of immuno therapy in the treatment of recurrent abortion has highlighted interest in this area. The use of immunological techniques for contraception are in their infancy but offer much hope for the future.

Material for this book was gathered in the early 1980's in Manchester, where a higher incidence than usual of complications in the gastro-intestinal and urinary tract was observed. Part I describes the principles and methods of radiotherapy for pelvic tumours, pathological features and radiological analysis of bowel and urinary tract changes. Parts II and III are devoted to clinical assessment and management, where the need for a multi-diciplinary approach is emphasized.

Ovarian carcinoma continues to be responsible for more deaths than all other gynecologic malignancies combined, due to a continued inability to achieve detection of early (rather than advanced) stage disease and the lack of effective tumor-specific therapeutics.

Ovarian carcinogenesis, invasion, and metastatic dissemination require a complex cascade of interrelated genetic, molecular, and biochemical events that regulate the neoplastic transition of normal ovarian surface epithelium.

This updated second edition includes exciting new advances in ovarian cancer detection and treatment and provides an analysis of current research into aspects of malignant transformation, growth control, and metastasis. A more detailed understanding of these processes may ultimately translate into the development of novel approaches for the detection and control of ovarian cancer.

The European School of Oncology came into existence to respond to a need for information, 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 Universities 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.

Pathology of Multiple Pregnancy collates case material from over 500 autopsies (including embryos) and 1200 placentas from twins, triplets, and higher multiples with selected literature on human multiple reproduction. It emphasizes important new concepts of pathophysiology and interpretation of less than ideal outcomes of multiple conception based on over 30 years experience in the field. Aspects of perinatal pathology unique to twins and higher multiples are emphasized, with practical suggestions for the service pathologist, including items of potential medico-legal significance. Controversial topics, such as the value of studies of concordance for diseases or malformations, and the significance of inter-twin anastomoses, are addressed and suggestions made for further investigation. A close working relationship between pathologists and clinical colleagues is encouraged by discussion of clinico-pathological correlations. And, the most recent discussions on mechanisms of twinning and genetic versus environmental influences on the development of twins are presented.