The hypothesis that cancer of the cervix is infectious was raised more than 150 years ago (Rigoni-Stern 1842). The first cell-free transmissions of papillomas were reported 95 years ago (McFadyan and Hobday 1898). A report of cell- free trans-mission of human warts was published in 1907 (Ciuffo). Thus, since these initial discoveries papillomavirus research has had to go a long way before it became possible to link these infections to cancer of the cervix (Durst et al. 1983; Boshart et al. 1984). Table 1 lists a selection of the publications that form the basis for our present understand- ing of the role of human pathogenic papillomaviruses (H PV) in human cancers. The identification of specific H PV types in cervical cancer in 1983, 1984 and in subsequent years substantially boosted activities in papillomavirus research. In part this is because cancer of the cervix ranks first in cancer incidence in develop- ing countries and is an important cause of cancer death in affluent societies (Parkin etal. 1984; I.A.R.C. 1989). Premalignant cervical lesions, particularly in affluent soci- eties, also contribute considerably to morbidity. Moreover, the availability of cell lines harboring H PV DNA and the identification of H PV genes as oncogenes have permitted in vitro analyses of H PV genome persistence, gene expression, and gene functions.

Reproductive medicine is the most dynamic area within obstetrics and gynecology and, arguably, the most complicated. An explosion of scientific understanding and technological capabilities - particularly in contraception, infertility and menopause - has transformed the specialty into a high-profile subject that touches upon endocrinology, embryology, andrology, surgery, social science, and practical law and ethics. The Oxford American Handbook of Reproductive Medicine provides a practical overview of the reproductive system and a systematic approach to its disorders, covering diagnosis, assessment, and ongoing management with particular emphasis on common and important presentations. Concise, readable, and pocket-sized, this handbook is useful for medical students, primary care clinicians, and ob/gyn residents as a ready reference for daily practice.

At the Mie International Symposium held in Japan in April 1994, leading scientists reviewed recent advances in the understanding of the contractile mechanism in smooth muscle. The present volume collects the papers presented at the symposium, summarizing the latest advances in smooth muscle function and emphasizing important components of the contraction-relaxation cycle. Topics include a discussion of the smooth muscle cell membrane, with emphasis on its ion channels; the regulation of cytosolic Ca2+ levels and the relationship to force in smooth muscle; aspects of the two key regulatory enzymes involved with myosin phosphorylation-dephosphorylation; the molecular basis for pharmacomechanical coupling in smooth muscle; developments in the basic contractile mechanisms involving the crossbridge cycle of tonic and phasic muscle; the role of myosin light chains; and many others. The approach is broad and presents contemporary opinions in pharmacology, physiology, and biochemistry as they relate to smooth muscle function. The book will appeal not only to those working in these disciplines, but to vascular clinicians, obstetric-gynecological physicians, and gastroenterologists as well.

When presented with the task of editing a volume on such a wide When presented with the task of editing a volume on such a wide and and diverse diverse topic topic as as Ovarian Ovarian Pathology, Pathology, it it is is difficult difficult to to know know how how to to limit limit the the range range of of subjects subjects to to be be covered covered when when there there are are so so many many taxonomical taxonomical entities, entities, both both neoplastic neoplastic and and reactive reactive that that could could be be included. included. However, However, I I have have chosen chosen to to cover cover concepts concepts that that are are not not usually usually dealt dealt with with in in depth depth in in Gynaecological Gynaecological Pathology Pathology textbooks. textbooks. From From the the clinicopathological clinicopathological viewpoint, viewpoint, a a wealth wealth of of new new data data has has been been updated updated and and critically critically reappraised. reappraised.

For doctors and students who wish to learn ultrasonography concisely yet comprehensively. The authors present the subject both systematically and practically, and with the facility of quick reference in mind, making generous use of flow-charts, tables and teaching-points. All general aspects of diagnostic ultrasound are covered, concentrating on those disorders encountered in the daily routine of scanning, but also referring to rarer conditions which need to be considered in differential diagnosis.

Urinary incontinence is a humiliating disability and a common problem in gynaecological clinics. In some centres specialised facilities are avail able for its investigation and treatment but in most hospitals the general gynaecologist has to manage this difficult condition. For both generalist and subspecialist it is timely to summarise advances in our knowledge of normal and abnormal micturition. Since 1973 the Royal College of Obstetrician's and Gynaecologists, through its Scientific Advisory Committee, has convened Study Groups on important growth areas in our specialty. The College invites an international panel of leading researchers to participate in a workshop, allowing time for in-depth discussion as well as the presentation of papers. It is hoped that this will produce not only an up-to-date sum mary of current knowledge but also a useful interaction between indi viduals and between specialties. This book is the result of the 21st Study Group, which was held in October 1989. The participants included urological and colorectal surgeons and a neurologist, as well as scientists and gynaecologists. The meeting began with sessions on basic science and advances in the investigation of the lower urinary tract, then covered voiding diffi culties, genuine stress incontinence and detrusor instability, before a final session on the relationship between urinary incontinence and ali mentary tract problems. The discussions formed an essential part of the meeting, and it is hoped that the lightly edited versions reproduced here will convey to the reader the stimulating atmosphere of the Study Group.

Changing approaches to diagnosis and clinical management of the uterus are comprehensively examined in this book. It gives a concise update of new concepts in physiology and pathology and their application in clinical practice. The book is designed especially for the gynecologist actively involved in patient care. Topics discussed include the pathophysiology of diethylstilbestrol (DES) changes, the immunology of the uterus, papillomaviruses and cervical neoplasia, endocervical carcinoma, mesenchymal tumors and diagnostic procedures such as colposcopy of the cervix, hysterosalpingography, and magnetic resonance imaging. The status of contemporary management is presented for hysteroscopy and hysteroscopic surgery, the congenital absence of the uterus and vagina, anovulatory dysfunctional uterine bleeding of the adolescent, uterine leiomyomata, genital prolapse, endometrial adenocarcinoma and childhood rhabdomyosarcoma of the vagina and uterus.

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.

This practical handbook provides detailed guidelines on prescribing drugs in all classes and for a wide variety of diseases and disorders during pregnancy, with numerous boxes and tables to assist understanding. CONTENTS: Introduction to Drugs in Pregnancy * Antimicrobials during Pregnancy: Bacterial, Viral, Fungal, and Parasitic Indications * Cardiovascular Drugs during Pregnancy * Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy: Embryotoxic versus Fetal Effects * Antiasthma Agents during Pregnancy * Anesthetic Agents and Surgery during Pregnancy * Antineoplastic Drugs during Pregnancy * Analgesics during Pregnancy * Anticonvulsant Drugs during Pregnancy * Psychotropic Use during Pregnancy * Antihistamines, Decongestants, and Expectorants during Pregnancy * Nutritional and Dietary Supplementation during Pregnancy * Use of Dermatologics during Pregnancy * Drug Overdoses during Pregnancy * Miscellaneous Drugs during Pregnancy: Tocolytics, Immunosuppressants, and Biologic Therapeutics * Substance Abuse during Pregnancy * Online Support Material

an adequate oxygen supply is vital for the undisturbed development of the fetus and its functions. This book gives a synopsis of the ruling influence that oxygen has in multiple regulation sytems in the mother and especially in the fetus. The authors consider oxygen as a manipulated variable or as a corrective element during normal pregnancy, during delivery and during acute and chronic oxygen deficiency. Furthermore, they deal with the consequences that oxygen deficiency has on the fetus.

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.

Advances in breast cancer research, achieved through the progress of knowledge and development of new therapies, have been translated into improved quality of care for breast cancer patients. Clinical investigations and clinical trials have made the largest contribution to the body of knowledge that finds its way to the patient. Never before during the past decades of management of breast cancer has there been such a fruitful intellectual cross-fertilization of ideas among individuals involved in the generation of hypotheses, basic research, development of drugs and treatments, conduct of clinical trials, and statistical evaluation - the results of all of which are now translated into progress in clinical care. Even issues such as the quality of life of breast cancer patients, once the domain for few, are now being openly addressed by trials and discussed in a much broader forum. The IVth International Conference on the Adjuvant Therapy of Primary Breast Cancer, also known as the st. Gallen Conference, was again attended by more than 800 scientists and clinicians interested in this broad spectrum of breast cancer research and the interactions between such diverse fields of interest and specialties as cancer pathology, molecular biology, and psychosocial oncology. This volume collects findings and conclusions presented at the conference.

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.

Sixty years ago, G. Fanconi published a paper entitled: "Familiiire infantile pemiziosaartige Aniimie (pemizioses Blutbild und Konstitu- tion)", in which he reported that this type of severe aplastic anemia represents a hereditary disease distinct from other pancytopenias of childhood (Fanconi 1927). Later this syndrome was named Fan- coni anemia (FA; van Leeuwen 1933). A more recent study of the genetics of FA confirmed that the syndrome is inherited in an au- tosomal recessive manner (Schroeder et al. 1976). Prenatal diagno- sis in FA families showed that about 25% of fetuses are affected (Auerbach et al. 1985, 1986). In 1964, Schroeder et al. discovered high frequencies of chro- mosomal aberrations in cultured peripheral blood lymphocytes from patients with FA. Schuler et al. (1969) reported that cells from FA patients are particularly sensitive to the chromosome-breaking activity or clastogenic effect of a polyfunctional alkylating agent. Since that time, studies of baseline and induced frequencies of chromosomal aberrations have been used for the identification of patients with FA. There is now a large body of data concerning the possible mechanism(s) underlying the hypersensitivity of FA cells to DNA cross-linking agents, the biochemical basis for which is still unknown. Complementation analysis, using cells from different FA pa- tients, has demonstrated genetic heterogeneity in the syndrome.

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."

The ultimate "consumer" of the data presented at conferences on the primary treatment of operable breast cancer is the patient, and when, as in this disease, the benefits of therapy are relatively mod est, the availability and interpretation of the data from trials be comes an issue of primary importance. The effects of present treat ment are in fact such that more patients relapse despite therapy than are estimated to benefit from it. It is, therefore, extremely dif ficult for the physician to recommend unequivocally one particular adjuvant treatment modality for the vast population of women with breast cancer. The interpretation of results from clinical research-oriented pro grams is constantly applied, however, in the treatment of breast cancer patients outside of clinical trials. From presented or publish ed data, many physicians extrapolate indications for the use of a given treatment regimen for their patients, perceiving it as the "best available therapy. " It is essential that the "best available therapy" be selected individually for each patient. However, considering the modest effect of treatment upon outcome, it is imperative that those who provide the data - those who are involved in both pa tient care and clinical research - make it known that the best cur rent treatment for the population of breast cancer patients is avail able within the framework of clinical trials. In this way not only present-day patients but also future ones will derive the greatest benefit.

Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

In the last decade of the 15th century a new and deadly disease called Morbus Gallicus, or syphilis, appeared and spread rapidly throughout Europe. The effects of syphilis were so severe that it, and those suffering from it, where regarded with horror and despair. It is difficult for the modern reader to appreciate the fog of confusion which surrounded sexually transmitted diseases in earlier times. Those suffering with these diseases were often condemned as victims of their own "sinful lust of the flesh"; a judgement attitude which hindered most of the early attempts at control and treatment. Despite this general attitude, there were some doctors who persevered in their attempts to understand the causes and discover treatments for syphilis and other sexually transmitted diseases. The Scars of Venus is illustrated with pictures of people, places, instruments and documents. It presents the historical background and achievements of the early venereologists through to the current venereologists' fight against HIV. This book will be of interest to anyone concerned with venereal diseases: doctors, nurses, counsellors, laboratory workers, medical historians, and those working in the areas of public/world health and the spread of infectious diseases.

The number of studies on chronic and recurrent pain bears no relation to the frequency of these complaints in gynecologic practice, nor to the clinical and scientific problems that still need solving in this area. Several factors stand in the way of progress in this field, such as the strongly subjective nature of the complaints, the frequent lack of correlation between them and objective findings, and the complexity of the psychosomatic interac tions involved. Although progress in our knowledge has been much slower than we would have wished, and although we are well aware of these many gaps, it was considered useful to gather in a book what we think we have learned during 3 decades of active interest in pain patients and pain problems in gynecologic practice and 12 years of supervision of a pain clinic in the Department of Obstetrics and Gynecology of Leuven University. As there are many differences between acute pain - clinical as well as experi mental - on the one hand and chronic pain symptoms on the other, it was felt preferable to limit the scope of this book essentially to chronic and recurrent pain in gynecologic practice. When presented with a complaint of lower abdominal and/or low back pain, the gynecologist should constantly be on the lookout for nongynecologic causes, of which the most frequent will be either gastroenterologic or orthopedic and sometimes urologic. I have been fortunate in obtaining the collaboration of Dr."

During the past ten years numerous new findings have been documented in the field of gynecological pathology, especially in respect of neoplasms. These findings have been generated by the application of recently developed techniques of immunology and molecular biology. However, clinicopathologic examinations. are still an absolute requirement for the morphologic evaluation of neoplasms, including gynecological tumors. The International Society of Gynecological Pathologists (ISGYP) has contributed greatly to the progress within gynecological pathology. The ISGYP Nomenclature Committee has promoted the International Histological Classification of Gynecological Tumors under the auspices of the W orid Health Organization. A new edition of the classification of tumors and tumor-like conditions of trophoblastic disease, uterine corpus, cervix, vagina, and vulva is currently in press. A second volume covering the ovaries, fallopian tubes, broad ligament, and female peritoneum will be published later. Organization of scientific symposia and seminars has also been an important activity of the ISGYP. The present editor organized and chaired a symposium entitled "Recent Progress in Diagnostic Pathology of Gynecological Tumors" held in Sendai, Japan on 11 April 1986 in close cooperation with Prof. T. Okagaki, University of Minnesota Medical School, and under the joint auspices ofthe ISGYP and the Japanese Society of Pathology. The following topics were discussed at this symposium: - Immunocytochemistry of gestational trophoblastic disease (Dr. R.J."

This book is the product of long years of close collaboration between two physicians, a pediatric endocrinologist and a pediatric surgeon, who are interested in the complex field of human malformations. Their efforts have set a new standard in the treatment of children with intersexual or mal formed female genitalia. It is impossible to convey the details of complex surgical procedures without the help of meticulous illustrations. It is fortunate that happened to meet an academically trained artist, Mrs. Siri Mills, M.A., while visiting in the United States. Her excellent knowledge of anatomy, her remarkable skills as an artist and technical illustrator, and her readiness to include all details of interest to the surgeon have found their fruitful expression in the illustrations of this book. We express our thanks to Springer-Verlag and especially to Prof. Diet rich Goetze, at whose suggestion this book was written, for their amiable compliance with all our wishes, and particularly for their willingness to retain Mrs. Mills as our illustrator. Munich, May 1985 WALDEMAR HECKER Contents In trod ucti on 1 Part 1: Endocrinologic Diagnosis in Pediatric Patients with Genital Anomalies General Rules . . . . . . . . . . . 4 Endocrinology of Antenatal Sex Differentiation 6 Male Differentiation 6 Female Differentiation 7 Specific Endocrinologic Diagnosis and Therapy 8 Virilization of the Female External Genitalia 8 Congenital Adrenogenital Syndrome with a Defect of 21-Hydr- ylase . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Intersexual Genitals Due to Deficient Androgenization of the Male 11 Defects of Testosterone Biosynthesis 11 Androgen Receptor Defects . . ."

March 23 and 24, 1983 saw the fIrst international symposium held under the auspices of the Wilhelm Vaillant Foundation for the Advancement of Pro- phylactic Medicine in the I. Frauenklinik der Ludwig Maximilians Univer- sitiit Miinchen. This symposium was concerned with Advances in Early Detection and Treatment of Breast Cancer and brought together patholo- gists, gynecologists,and radiologists from Denmark, England,France, Italy, Sweden, Switzerland, the German Democratic Republic, and the Federal Republic of Germany. The fIrst session dealt with problems concerned with the biology, patho- genesis, and histopathology of early carcinoma of the breast, with special reference to the clinical aspects. The second session was taken up with topi- cal developments in the early diagnosis of breast carcinoma and indicated the present limitations of early diagnosis. In the third session the latest results of the experiences by groups working on the treatment of early carci- noma of the breast in France, the United Kingdom, Italy, the United States of America, and the Federal Republic of Germany were discussed. The main emphasis lay on conservative treatment methods with complete or partial preservation of the breast. These vary quite widely. Some of the conclusions presented on the basis of long-term clinical studies must be regarded as signifIcant breakthroughs, and at the stage these have reached they must no longer be overlooked. The symposium has highlighted numerous unsolved problems and made it clear that conflicting opinions abound.

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.