Recent advances in molecular biology have provided new dimensions in the study of the reproductive system. There has been major progress in our understanding of the molecular mechanisms of hormone action in the past few' years. The symposium on "Molecular Basis of Reproductive Endocrinology" was organized to highlight new research findings on the regulation of the hypothalamic-pituitary-gonadal axis. The emphasis of the symposium was on physiological questions answered by the molecular biology approach. Studies on the functional relevance of gonadotropin releasing hormone and LH and FSH gene expression were presented, together with research on the molecular biology of ovarian and testicular steroidogenic enzymes and protein hormones. Also, several novel aspects of hormone gene expression in placental tissues were reviewed. The symposium was held July 25 to 26, 1991, immediately prior to the 24th Annual Meeting of the Society for the Study of Reproduction, on the campus of the University of British Columbia in Vancouver. Serono Symposia, USA generously financed and coordinated the meeting. We are indebted to Dr. Bruce K. Burnett and Dr. L. Lisa Kern for their professional assistance in the organization of the symposium. We would also like to thank Drs. Victor Gomel, Basil Ho Yuen, and John Challis, who served as session moderators. Most of all, we truly appreciate the efforts of all the invited speakers, poster presenters, and discussants in making this a memorable event as the largest one-day meeting of the Serono Symposia USA, series.

Although neonatal screening was begun only 20 years ago, and is consequently still in its early stages, it is already a classic example of efficient preventive pediatrics. At present, routine neonatal screening covering a satisfactory percentage of newborn babies is carried out in only a small part ofthe world. For some five diseases enough infants have been screened to give reasonably reliable information about the frequency of these diseases in various populations. Interesting differences are beginning to appear in popula tions of different ethnic and racial background. The medical importance of neonatal screening is especially obvious in metabolic diseases that are not too rare and for which effective treatment depends upon an early diagnosis, such as phenylketonuria, galactosemia, and - a more recent screening pro gram - hypothyroidism. About 1 of 4000 newborns is affected with hypothyroidism and can receive timely substitution with thyroid hormone. Of 34.5 million babies tested for phenylketonuria, 3000 cases have been diagnosed in time to prevent mental retardation by means of dietary therapy."

Over a mere 5 years, neonatal cranial sonography has evolved from an obscure and largely experimental imaging possibility to the modality of preference in the examination of the young brain. The almost immediate acceptance of the ultrasound examination of the neonatal brain was based on a number of coinci dent factors, the most important of which was the emergence of a burgeoning population of premature neonates who were, for the first time, surviving be yond infancy. These delicate patients were beginning to withstand the rigors of extrauterine life when not fully prepared for it; pulmonary, cardiac, and infec tious diseases no longer claimed most of them. With survival, a new specter reared its head: Would the eventual mental and neurologic status of these same children be worth the expense and time needed to bring them through their first months? This issue became increasingly pressing as evidence mounted through the 1970s that very premature neonates were at a high risk for intracranial hemor rhage and posthemorrhagic complications. An imaging modality that could evaluate the premature brain was sorely needed. The CT scanner with its proven ability to diagnose intracranial hemorrhage was of little value in this regard. So too were static gray-scale or waterpath ultrasound units. These modalities all had the same limitation, lack of portability. As neonatal intensive care units proliferated, so did the technology that would soon allow cribside neonatal neuroimaging, the real-time sector scanner."

Very thorough knowledge of breast pathology is a sine qua non for interpretation of breast films ... progress in X-ray diagnosis could only be made by careful comparison of the film with the actual specimen. H.INGLEBY Multiplication of the same e"oneous diagnosis does not make that diagnosis co"ect. J.G.AzZOPARDI Paradoxically enough, our specialty considers the radiologist who mis takes a skin fibroma or the calcifications in a sponge kidney for a kid ney stone to lack basic knowledge, while the radiologist who imme diately calls for the surgeon because of a few white spots on a mammogram is thought to be acting according to the rules of medical practice. Misunderstandings and confusion with regard to breast pathology as well as the comfortable philosophy that superfluous biopsies are the price we have to pay for the early detection of carcinomas have in many places led to a loss of confidence in mammography. Yet this is a meth od with which carcinomas can be detected earlier than with any other imaging technique.

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 multidiscipli nary 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 on cology."

The purpose of this series of volumes is to present a comprehensive view of the complications that result from the use of acceptable diagnostic and thera peutic procedures. Individual volumes will deal with iatrogenic complications involving (1) the alimentary system, (2) the urinary system, (3) the respiratory and cardiac systems, (4) the skeletal system and (5) the pediatric patient. The term iatrogenic, derived from two Greek words, means physician-in duced. Originally, it applied only to psychiatric disorders generated in the patient by autosuggestion, based on misinterpretation of the doctor's attitude and comments. As clinically used, it now pertains to the inadvertent side effects and complications created in the course of diagnosis and treatment. The classic categories of disease have included: (1) congenital and developmen tal, (2) traumatic, (3) infectious and inflammatory, (4) metabolic, (5) neoplastic, and (6) degenerative. To these must be added, however, iatrogenic disorders a major, although generally unacknowledged, source of illness. While great advances in medical care in both diagnosis and therapy have been accomplished in the past few decades, many are at times associated with certain side-effects and risks which may result in distress equal to or greater than the basic condi tion. Iatrogenic complications, which may be referred to as "diseases of medical progress," have become a new dimension in the causation of human disease."

Early embryonic loss is a continuing social and economic global problem. In human populations the estimates of interruptions early in pregnancy range from 35-60%. In animal husbandry (swine, ruminants) fully 30% of pregnancies fail to survive early events of gestation. The futility associated with this persistant high risk is even more unsettling because of advances made in assisted reproductive technology which, although this very selective methodology has added to our knowledge of embryo-endometrial interactions, has resulted in a birth rate of only 14%. These studies have instigated comparisons of the live relative contributions of the embryo and the uterus to the outcome of pregnancy. These analyses have shown that we have learned significantly less about the role of the uterus in deciding the outcome of either natural or assisted pregnancies. In 1979 a quotation by George Corner was used to set the tone of a meeting that was devoted to discussion of the cellular and molecular aspects of implantation. In spite of the proliferation in research activity which occurred in the following 15 years our real understanding of the embryo transfer process has fallen short of our expectations. We use the Corner quotation, once again, to preface this symposium so that we may recall that the fundamental nature of the process which regulates embryo-endometrial interactions still escapes us.

This series of volumes dealing with reproductive health care has as its primary objective the improvement of the quality of human reproduction. The of knowledge and new technology give us opportunities as never explosion before to accomplish this end. The Editor has brought together contributors who are outstanding scientists from around the world. A number of the authors have personally made significant contributions to our body of knowledge in reproductive medicine. Bringing all this information together in an easily readable format is a great service. This is essential reading for all concerned with the control and improvement of human reproduction and the correction of its many deficits. xv P'art I Physio-anatom-ical Parameters 1 Uterine microvasculature and spontaneous abortion M. TAKADA In the implantation and subsequent development of a fertilized ovum, its integrity is most significant. However, with maternal local factors, i.e., unsatisfactory uterine conditions, implantation may not succeed even if the integrity of the fertilized ovum is excellent; if implantation is made, the maturation of the fetoplacental unit following implantation is disturbed, which leads to abnormalities in fetal development or to miscarriage. Thus, the uteroplacental unit, as well as the fetoplacental unit, plays an important role in the establishment and maintenance of pregnancy. Among the mechanisms of the utero placental unit, most significant is the physiological mechanism of the uterine microvasculature and its correspon dence to gestation. In particular, homeostasis of simultaneous cooperative development of the uterine wall and the placenta is most important."

Decision making in modem obstetrics and perinatology is con trolled by a variety of different factors, but there is little doubt that in industrialized countries one of the most powerful single factors is the concern and fear of causing permanent brain damage in the unborn and newborn. The dramatic increase in the rates of abdom inal deliveries in many parts of the world is certainly rooted to a substantial part in the bstetrician's concern not so much about possible perinatal death, but more so about permanent brain dam age in surviving children. This trend has been accelerated by the increasing number of litigations in connection with brain damage observed in many societies. This problem itself has many aspects, but it seems evident that litigation - justified or unjustified - is one modem expression of the human and social tragedy inflicted on individuals and families by the birth of a brain-damaged child. The medical, social, and human importance of the problem is in sharp contrast to the relative lack of scientific knowledge avail able. This became very clear when the National Institutes of Health published the excellent review in 1985 on "Prenatal and Perinatal Factors Associated with Brain Disorders" and its editor, J. M."

Various scientific evaluations taken from these chapters were presented during the international symposium, 'Carcinoma of the Cervix, ' which was held from September 4-7, 1980 in Kiawah Island, Charleston, South Carolina, U.S.A. An international selection of research investigators have contributed reviews designed to be informative to medical, graduate and post-graduate students, as well as clinicians, oncologists and investigators working in the area of female carcinoma. An attempt has been made to provide a total coverage of current progress in carcinoma of the cervix. In particular, the following major areas are included: Epidemiology, Histology & Histochemistry, Ultra structure, Physiology & Biochemistry, Genetics & Cytogenetics, Immunology, Diagnosis, and Patho physiology & Complications. Major changes have occurred in incidence and mortality rates for carcinoma of the cervix in the past decade. Mass screening programs and their ability to detect earlier stage diseases have attributed to a reduction in invasive diseases. Most cervical cancers could be prevented by an extension of cytologic screening programs in high risk areas. Greater resources must be provided to reach high risk areas in order to prevent the occurrence of cervical cancer."

The concept of the foeto-placental unit as an integrated endocrine organ has been defined recently by many in vivo studies at the 17th- 20th week of gestation. A functioning foeto-placental unit is necessary for most of the increased oestrogen production of pregnancy and for the provision of glucocorticoids and aldosterone to the foetus. Neither the foetus nor the placenta alone have the necessary enzyme systems for the synthesis of these groups of steroids. However, when the foetus and placenta function as a unit, all of the enzyme systems are present for the synthesis of these steroids from circulating cholesterol. The placenta, but not the mid-gestation foetal adrenal, can synthesize physiologically significant amounts of pregnenolone from circulating cholesterol. Part of the pregnenolone is converted to progesterone in the placenta by the 3 -HSD system (absent in the foetus). The progesterone is transferred to the foetus where it is transformed by C-II, C-17, C-18 and C-21 hydroxylases (all absent in the placenta) to cortisol, corticosterone and aldosterone. Pregnenolone transferred from the placenta to the foetus undergoes 171X-hydroxylation, side chain splitting and sulfurylation (absent in the placenta) and is converted to DHAS. The DHAS may undergo 161X-hydroxylation (absent in the placenta) in the foetal liver and be transported to the placenta as 161X-OH-DHAS. There it is subjected to a neutral steroid sulfatase (absent in the foetus) and is converted to oestriol by action of the 3 -HSD system and the aromatizing enzyme system."

by Dr. Donald L. King The past decade has seen the ascent of ultrasonography to a preeminent position as a diagnostic imaging modality for obstetrics and gynecology. It can be stated without qualification that modern obstetrics and gynecology cannot be practiced without the use of diagnostic ultrasound, and in particular, the use of ultrasonogra phy. Ultrasonography quickly and safely provides detailed, high resolution images of the pelvic organs and gravid uterus. The quality and quantity of diagnostic information obtained by ultra sonography far exceeds anything previously available and has had a revolutionary impact on the management of patients. High resolution static images permit the intrauterine diagnosis of fetal growth retardation and fetal abnormalities. In addition to tradi tional images, newer dynamic imaging techniques allow observa tion of fetal motion, cardiac pulsation, and respiratory efforts. The use of ultrasonography for guidance has greatly augmented the safety and utility of amniocentesis. One of the great virtues of diagnostic ultrasound has been its apparent safety. At present energy levels, diagnostic ultrasound appears to be without any injurious effect. Although all the availa ble evidence suggests that it is a very safe modality and that the benefit to risk ratio is very high, the actual safety margin for its use Vll as yet remains unknown. As a consequence, practitioners are urged to limit its use only to those situations in which genuine clinical indica tions exist and real benefit to the patient is likely to result."

Extensive basic research and clinical trials have in some aspect of reproductive physiology, gyne been conducted on inert and medicated intrauterine cology, or family planning. There is in this volume devices. In the last decade, substantial progress has an attempt to provide a total coverage of current been made in understanding the modes of action progress in medicated intrauterine devices. The and the physiological mechanisms of IUDs - pro volume is intended for a broad readership, includ gress resulting from modern techniques and in ing physicians, medical workers, medical personnel, strumentation in microanatomy, immunology, pa and administrators in family planning. It is hoped thology, endocrinology, biochemistry and biophy that this volume will serve as a stimulus to basic sics. Such studies, however, are scattered in such a scientists and clinicians concerned with intrauterine wide spectrum of journals that the clinician and devices to intensify their research toward better family planner can hardly keep up to date with the contraceptive techniques. advances. An attempt is made in this volume to coordinate physiological and clinical parameters. Little is September 1980 known about the possible role of diet, diseases and environmental factors. E. S. E."

The motive to prepare this volume on antibiotics for the physician caring for women was based upon the editor's perception that the subject matter had never been fully developed for the obstetrician-gynecologist. Most textbooks of infectious disease have a small section devoted to antibiotics, which has little relevance for the physician caring for post-operative or post-partum infections. Basic antibiotic pharmacology is described and there is a reflex prohibition of antibiotics for the pregnant woman. Correctly, the reader assumes that the authors themselves do not care for women with bacterial infections of the pelvis. Recent texts in infectious disease in obstetrics gynecology have been little better. Although the focus has been more clini cally oriented, space requirements have too often kept the discussions at a superficial level. A total focus upon antibiotics in this volume eliminates the restraints of space in prior publications. The greatest reward in my task as editor of this volume is related to the quality of the individual authors. They range from former students, to con temporary colleagues, to respected peers in infectious disease. Since the quality of this volume is related to the sum total of the individual chapters, I wish to comment about each of the contributors. Philip Mead from the University of Vermont is an old friend, who brings to the question of prophylactic antibiotics, his wide clinical experience and encyclopedic knowledge."

The aim of this book is to transmit the message that asphyxia is the major cause of infant mortality in the ne asphyxia-if severe, caus onatal period. The sequelae of ing cerebral palsy; if mild, leading to MBD to seizures are all potential risks. It is important to make young physicians and nurses aware of this complication of the birth period, how to avoid it, and how to treat it. Facilitating such awareness is the chief purpose of this book. Alberto Lacoius-Petruccelli New York 7 Contents 1. Asphyxia: Definitions, History, and Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2. Occurrence in Utero, at Birth, and after Delivery ................................. 17 3. Physiopathology of Asphyxia and Its Staging .................................. 21 4. Work-up and Treatment in the Newborn: Delivery Room, Nursery, and Perinatal leU 25 5. Mechanical Ventilators .................... 31 6. Prognosis ................................ 37 7. Brain Asphyxia and Hemorrhage ., ........ 51 8. Types and Stages of Fetal Anoxia: Anoxic, Anemic, Stagnant, and Histotoxic ......... 57 9. Embryonic and Fetal Periods .............. 65 10. The Placenta: Origin and Functions ........ 77 9 CONTENTS 10 11. Fetal Circulation 87 12. Placental Insufficiency or Dysfunction ..... ."

The birth of a baby is the culmination of months of anticipation and plan ning. Most often, mother and infant are healthy and readily able to estab lish close contact-a bond. However, in some situations either mother or baby or both present complications. The more prompt and rational the treatment, the sooner the normal parent-infant relationship will commence. This book is devoted exclusively to the first days following birth. In its 15 chapters, postpartum and postnatal physiology and pathophy i: .;logy are reviewed by 18 specialists. Normal and abnormal development of mother and child is correlated with proven means of clinical management. Chapters 1 through 3 cover maternal postpartum developments and complications. Chapter 4 stresses the importance of a normal parent newborn relationship, a concept of increasing concern in modern society. The following ten chapters discuss neonatal physiology and pathophysi ology; the effects of obstetric anesthesia on infant behavior, pulmonary function measurements in the postnatal period and treatment of the sick newborn are discussed in detail. The final chapter reviews maternal and perinatal mortality; the data, based on extensive surveys in New York City, indicate that current management is effecting an overall decline in mortality."

The Fourth International Congress on the Menopause was held in Lake Buena Vista, Florida, USA in October - November 1984. It was different from the previous meetings held under the auspices of the International Menopause Society in three respects: the duration of the Congress was extended to five days, plenary sessions were held on each day, and the scope of the subject matter was expanded to provide a total or holistic overview of the subject - hence the theme for the Congress 'Climacteric Medicine and Science: A Societal need. ' In recent years there has been an increased interest in the menopause and middle year aging by scientists and clinicians in fields as diverse as anthropology, urodynamics, nutrition and exercise physiology, while 'newer' issues in clinical medicine, such as osteoporosis prevention and management, attracted specialists in nuclear immaging techniques and internal medicine. Over 120 invited speakers plus numerous contributors to the free communication, special lectures and the poster sessions provided a virtual cornucopia of information on the menopause, that has indeed brought a newer perspective to a subject previously the domain of a single specialty, the gynecologist, and dominated by a single therapy, estrogen replacement.

This is a unique book in that it brings together the two key investigative techniques in Gynaecology and Obstetrics, namely ultrasound and endoscopy. So often in the past they were regarded by their exponents as rival techniques but it is now recognised that they are complementary to each other. Consequently future trainees in endoscopy should become efficient in transvaginal sonography and vice versa. Ultrasound can be used to study the morphology of the pelvic organs such as the endometrium, myometrium and ovaries, and being non-invasive, safe and convenient can be repeated as often as is deemed necessary to monitor changes over time; for example in the investigation of the infertile woman the development of the dominant follicle, the maturation of the endometrium and the formation of the corpus luteum can be documented throughout the menstrual cycle while growth of ovarian cysts can be precisely measured to determine the need for surgery. A seldom-mentioned strength of the ultrasound examination is its interactive quality, for example by performing abdominal palpation during the scan, the mobility of the uterus and ovaries can be assessed. Also the images as they appear can be shown to the patient to aid understanding. Ultrasound can also determine function and the use of Doppler has been used for example to access endometrial receptivity, follicular maturity and the likelihood of malignancy in the endometrium or ovary.

This volume represents the Proceedings of the World Conference on Embryo Transfer, In Vitro Fertilization and Instrumental Insemination held on September 24-27, 1980 in Kiel, West Germany. Professor Dr. L. Mettler and Dr. H. H. Riedel of Frauenklinik der UniversiUit in Kiel were the local co chairpersons, who contributed very richly to the program. Basic research, clinical trials, preparation of manuscripts, editorial assistance and presentation of results were generously supported by the following institutions and organizations: Kulturministerium des Landes Schleswig-Holstein Medizinische FakuItat der Christian-Albrechts-UniversiUit, Kiel Wayne State University School of Medicine; Detroit, Michigan, USA C. S. Mott Center for Human Growth and Development; Detroit, Michigan, USA Universitats-Frauenklinik und Hebammenlehranstalt; Kiel, West Germany Serono GmbH; Freiburg, West Germany Hutzel Hospital; Detroit Medical Center; Detroit, Michigan, USA Deutsche Gesellschaft fUr Gynaekologie und Geburtshilfe; West Germany Deutsche Gessellschaft zum Studium der Fertilitat und Sterilitat; Sektion Andrologie Thanks are also due to Aponti GmbH (5000 Koln 21), Bayropharm GmbH (5000 Koln 80), Deutsche Lufthansa (5000 Koln), Organon GmbH (8024 Oberschleissheim), Winthrop GmbH (6080 New Isenburg), and Wisap GmbH (8029 Sauerlach), for financial assistance. Sincere appreciation and gratitude are due to the contributors who meticulously prepared their chapters; to Ms Jackie Mucci for editorial skills and assistance, and Ms. Jackie Smieska for editorial help. Thanks are also due to Dr. H. D. Brackebusch for his assistance during the conference; to Ms. E. Seiss for her secretarial assistance; and to Mr."

In recent years, papillomaviruses in general and human papillo maviruses in particular have been recognized as possible agents of important diseases, including some forms of human cancer. The purpose of this book is to present a concise panorama of the pre sent status of knowledge of this topic. This knowledge is as impor tant to molecular biologists and virologists as it is to clinicians and pathologists. To bridge the gap among these diverse groups of investigators, we conceived of a book covering a broad spectrum of the basic scientific, clinical, and pathological aspects of diseases associated with papillomaviruses. Although the principal thrust of this book is directed at human papillomaviruses, fundamental knowledge of animal viruses is essential to the current understand ing of the molecular mechanisms of cell transformation. For this reason, a chapter on animal viruses has also been included. Some of the experimental work having to do with the elucidation of transformation and other aspects of interaction between the virus and the cell cannot be based on human papillomaviruses because of a lack of suitable experimental models. Hence, some of the chapters dealing with fundamental aspects of viral molecular biol ogy are based on animal models. We were very fortunate in having persuaded a number of distin guished colleagues to contribute to this work."

Each new volume of this publication brings the privilege of expressing some of my thoughts on subjects of interest to its readers. In the past year or so public concern about environmental and societal dangers has largely turned to those of cosmic proportion-Chernobyl, the thinning ozone layer, AIDS, and the like-and thankfully our subject matter has been allowed a respite. Even the miniepidemic of craniofacial and other malformations caused by the retinoid antiacne drug Accutane made no headlines. Incidentally, this might have been a tragedy of far greater proportions had it not been nipped in the bud by the historical ground work that quickly permitted it to be recognized as due to an environ mental teratogen-the sort of fact the public and authorities inadequately appreciate. But there is a warning connected with this abeyance of media focus on teratological matters. Disquiet over cosmic imbalances will sub side as they are corrected or horrendous projections fail to materialize, and even cures for dread infectious diseases, or Puritan revolution in terdicting such plagues, will be forthcoming, and these things will occur long before congenital malformations are no more. And as the year-in and year-out recurrence of over 100,000 an nual births of seriously malformed infants in the United States alone continues to force itself on the public consciousness, we can expect a heightened demand that "a cure" be found, because "if we can land a man on the moon, if we can prevent polio, why can't we . . ."

Postpartum Depression: Causes and Consequences chronicles a decade and a half of research into this relatively common mood disorder experienced in various forms by between 10-40% of all women following delivery. The author has conducted three major studies all of which are presented in this volume. The most recent study comprises the bulk of the monograph and presents the results with regard to psychological, social and hormonal factors in postpartum depression and the blues. Information regarding the epidemiology, etiology and treatment of postpartum depression is also included. The work described in this volume represents the attempt by the author to begin to address several of the major unresolved questions regarding the prevalence, causes, and consequences of postpartum mood disorders. The important negative implications of poor maternal adjustment for both the new mother and her family as well as the increased awareness of childbearing women who are now demanding answers and information make this book indispensable for all practitioners in psychology, psychiatry and obstetrics-gynecology as well as for the students of these disciplines.

Current Perinatology, II, explores the most recent major research techniques utilized in the evaluation, diagnosis, and management of the high-risk mother and her newborn. The volume should be a major reference for pediatricians, perinatologists, and neonatologists, as well as for nurses and allied health personnel closely involved with the care of the high-risk mother, fetus, and newborn. Topics presented include perinatal Doppler; Doppler echocardiography of the human fetus; invasive fetal assessment by fetal blood sampling; prediction, prevention, and treatment of preterm labor; percutaneous umbilical blood sampling and intravascular fetal therapy; current and future perspectives for fetal genetic diagnosis; current concepts of substance abuse during pregnancy; newer methods of diagnosis and treatment of neonatal sepsis; clinical applications of neonatal pulmonary function testing; and current management of hypoplastic left heart syndrome. Discussions of stabilization and transportation of the critically ill obstetric patient and of pain management in the neonatal intensive care unit will be of interest to both physicians and nurses.