Recently, attention has been called to the role that microvascular organization plays in the functional morphology of all organs and tissues, both in normal and pathological conditions. Since its development by Murakami, the corrosion cast method for scanning electron microscopy has come to be considered one of the most efficient means in clarifying the three-dimensional features of the microcirculation of organs and tissues. Scanning Electron Microscopy of Vascular Casts: Methods and Applications was planned to supply fundamental and new information regarding microcirculation studies to general biologists, anatomists, pathologists and clinicians. The contributions to this volume, contain original findings and excellent electron micrographs obtained by using recently improved corrosion cast methods. The rich variety of papers in this book will be useful to many, and will provide both the basic and clinically oriented readers with good ideas, suggestions, and original and worthwhile information.

The title "Stem Cells from Cord Blood, In Utero Stem Cell Develop ment, and Transplantation-Inclusive Gene Therapy" suggests that more than one topic is combined in one workshop. Indeed, at first glance the recovery of stem cells from cord blood has to be seen as separate from the attempts to achieve effective in utero therapy by stem cell trans plantation, because the first issue deals with an innovative stem cell source as an alternative to bone marrow, which is already spreading rapidly in medical practice, whereas the second topic is still strictly ex perimental and only investigated in medical centers with the appropri ate background. It is, however, not only justified, but helpful to com bine the two topics in one workshop and consequently to cover them in the same volume of the Ernst Schering Research Foundation Work shop series, because they are intimately related and both based on the new insights into the biology of stem cells. Professor Werner Arber, the Nobel Laureate from the University of Basel, pointed out in his In- Professor Dr. W. Holzgreve VI Preface The participants of the workshop troductory Lecture that our understanding of hematopoietic stem cells as descendents of totipotent cells and our current approaches to using them in post-and prenatal therapy have been furthered significantly by genetic engineering technologies which are "artificial contributions to the process of biologic evolution.""

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.

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.

The pregnant host is at risk for any of the viral diseases her nonpregnant counterpart acquires. Additionally, pregnancy heightens our concerns regarding specific viral diseases be cause of their potential for enhanced adverse effects on both maternal and fetal well-being. All too often the obstetrician relinquishes responsibility for the management of the gravida infected by a viral pathogen, and those expert in infectious diseases are confounded by the influence of pregnancy on these conditions. A major goal of this textbook is to narrow the gap between the two aforementioned management dichotomies in the virally infected pregnant woman. Weare at the infancy of our understanding of viral infections in pregnancy. The current and anticipated advancements are due in large part to a burgeoning oftechnological achievements in the areas of immunodiagnostics, molecular biology, and pharmacotherapeutics. Our in utero diagnostic capabilities, both invasive and noninvasive, have also allowed us new opportunities to study the effects of various maternal infectious disease processes on the developing fetus. New insights have been recognized pertaining to the maternal-fetal interface, the placenta, in that this structure is now acknowledged to function as both a mechanical and an immunological barrier to vertical transmission of infection. These observations suggest that there will be an outpouring of new data in the next several years that clinicians will need to master to maintain an appropriate level of expertise in the care of their patients.

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.

The advent in the 1960s of the unique and exciting new form of energy called laser brought to medicine a marvelous tool that could accomplish new treatments of previously untreatable disorders as well as improved treat ment of mundane problems. This brilliant form of light energy is many times more powerful than the energy of the sun yet can be focused microscopically to spot sizes as small as 30 microns. Lasers can be directed into seemingly inaccessible areas by mirrors or fiberoptic cables or can be directly applied into sensitive areas such as the retina without damage to intervening structures. There has been a rapid proliferation in the use of lasers in all surgical specialties. Starting with bold ideas and experiments of "thought leaders" in each specialty, the application of lasers has evolved into commonplace usage. Beginning with the era when laser presentations and publications were an oddity, now nearly all specialty areas have whole sections of meetings or journals devoted exclusively to laser usage. Laser specialty societies within a specialty have developed and residency training programs routinely instruct trainees in laser techniques. Basic science and clinical experimentation has supported laser knowledge. Laser usage has also become international. Newer wavelengths and accessories have added to the armamentarium of laser usage. Despite the rapid growth in laser interest, no single source exists to instruct the many new laser users in proper, safe, and effective use of this new modality."

A growing majority of women in the western hemisphere have been delaying initiation of childbearing to later in life. Consequently, more than ever before, women in their late 30s to early 40s are attempting their first pregnancy. Since the incidence of most cancers increases with age, delayed childbearing results in more female cancer survivors interested in fertility preservation." Fertility Preservation in Females: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this unique and practical reference guide for reproductive endocrinologists, gynecologists, embryologists, reproductive scientists, and oncologists provides strategies for fertility preservation in women, using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms."

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.

Lymphatic mapping techniques have proven to be useful to the early detection and safe treatment of endometrial and cervical cancers; however, the techniques have much of value to offer for breast cancer also and particularly for vulvar cancer, where there has been an explosion of interest and research. In the new edition of Clinical Lymphatic Mapping of Gynecologic Cancers, the techniques are fully explained, with consideration of the latest developments and technologies.

Neurology and Pregnancy provides a comprehensive multidisciplinary guide to best practices for research and practicing neurologists, as well as obstetricians and other specialists caring for women with an acute or chronic neurological disorder. The book encompasses preconception care, genetic counseling, pregnancy in patients with chronic neurological disorders, and acute pregnancy-related neurological complications. Postpartum care and complications, including lactation concerns, are also addressed, as well as the long-term effects of pregnancy and its complications on maternal brain health. Vol 1 summarizes the complex neurophysiological changes in pregnancy from a basic and translational science perspective. This includes neuroimaging, principles of neuro-obstetric critical care, and ethical and medicolegal concerns, describes normal fetal cerebral development and summarizes the management of the most common prenatal neurological diagnoses. Vol 2 focuses on chronic neurological conditions in pregnancy such as epilepsy, migraine, and multiple sclerosis, as well as acute neurological disorders including preeclampsia/ eclampsia, ischemic and hemorrhagic stroke, and CNS infections. Each chapter introduction includes data on epidemiology, when applicable. In discussing management, comments of safety profiles of medications preconceptionally, during pregnancy and lactation are summarized. Each chapter includes 1-2 illustrative cases.

The state of health care is reflected by perinatal and neonatal morbidity and mortality as well as by the frequencies of long-term neurologic and developmental disorders. Many factors, some"without immediately recognizable significance to childbearing and many still unknown, undoubtedly contribute beneficially or adversely to the outcome of pregnancy. Knowledge concerning the impact of such factors on the fetus and surviving infant is critical. Confounding analyses of pregnancy outcome, especially these past two or three decades, are the effects of newly undertaken invasive or inactive therapeutic approaches coupled with the advent of high technology. Many innovations have been intro duced without serious efforts to evaluate their impact prospectively and objectively. The consequences of therapeutic misadventures character ized the past; it seems they have been replaced to a degree by some of the complications of applied technology. Examples abound: after ov eruse of oxygen was recognized to cause retrolental fibroplasia, its restriction led to an increase in both neonatal death rates and neurologic damage in surviving infants. Administration of vitamin K to prevent neonatal hemorrhagic disease, particularly when given in what we now know as excessive dosage, occasionally resulted in kernicterus. Prophy lactic sulfonamide use had a similar end result. More recent is the observation of bronchopulmonary dysplasia as a complication of re spirator therapy for hyaline membrane disease. The decade of the eighties opened with the all-time highest rate of cesarean section in the United States."

Professor Philip Bromage From the earliest stirrings of modern surgical anesthesia, novice surgeons struggling to learn from the living what there was a strong intuitive feeling that anesthesia of part they were denied an opportunity to learn from the dead_ of the body would be better for the patient than complete But that is largely nostalgia for a past era_ Today, the visual anesthesia of the whole organism. In 1848, James Young arts and the plastics industry have united to give us superb Simpson spent some time and effort seeking this elusive teaching models and techniques that did not exist a few goal, but after a few ingenious though unsuccessful experi decades ago, and they have developed two- and three ments, he gave up the search and turned back to general dimensional surrogate cadavers that are imbued with a anesthesia as the only practical solution to surgical pain more vivid artistry than ever existed on the marble slabs relief at that time_ amid the formalin reek of our old dissecting rooms_ earl Koller's simple but brilliant application of cocaine to This book is a fresh and highly successful attempt to repair some of the bridges that were burnt with the passing of the the eye in 1884 opened the door to a whole new universe of neural anatomy and pharmacology_ Within a decade or old anatomy days_ Together, the authors have contributed"

T HE prediction of the probability of the safe passage of the fetus through the birth canal is the primary function of the attendant at the start of labor. The means of determining the relative size of the fetal head and the internal diameters of the pelvis have therefore been the objects of deep concern down through the centuries. Manual techniques of clinical evaluation of cephalo-pelvic relations reached their peak a generation or two ago. A massive nomenclature existed with respect to pelvic planes and diam eters. To these were related various positions, attitudes, stations, and synclitisms of the fetal head. Measurements depended on digital efforts to explore the interior and on dubious implications drawn from external pelvimetry. The mechanisms of labor, as it might occur under the innumerable possible pelvic measure ments and fetal orientations, were the subject of hours of stu dent drilling and remained a lifelong preoccupation of the most seasoned specialist. The increasing safety of cesarean section somewhat miti gated the consequences of error. When a borderline internal conjugate was digitally determined, a trial labor might be per mitted with the assurance that an ultimate solution was in reserve. Mistakes of two kinds persisted, however. On the one hand, trial labor might be permitted to continue too long and, with penicillin not yet discovered, a delayed cesarean section v vi Foreword could be perilous. Alternately, to be on the safe side, many un necessary elective sections might be carried out.

The fetal period of human growth and development has become an area of intense study in recent years, due in large part to the development of diagnostic ultrasound. More than 2,000 articles have been published in the last five years describing anatomy and pathology in utero, as reflected in sonographic images. Yet, no stan dard reference exists to correlate these images with fetal gross anatomy and at tempts to draw parallels from adult structure have often led to false assumptions. The dictum "the newborn is not a miniature adult" is all the more valid for the fetus. This text aims to provide a comprehensive reference for normal sectional anat omy correlated with in utero ultrasound images. In addition, magnetic resonance images of therapeutically aborted or stillborn fetuses are paired with similar gross sections to serve as a foundation upon which current in vivo studies may build. Lastly, a miscellaneous section illustrates several anatomic points useful in the understanding of fetal anatomy. These points include the changing anatomy of the fetal brain during gestation and the anatomy of the meninges, the fetal heart, and ductus venosus. It is our hope that this atlas will provide a clear picture of fetal anatomy, rectify some of the confusion which exists in antenatal diagnosis, and stimulate further interest in fetal development."

The chapters in this book represent presentations at the first meeting ever held on the regulation and actions of follicle stimulating hormone. The meeting took place on the campus of Northwestern University, Evanston, Illinois, from October 25 to 28, 1990. The idea for this meeting was conceived by Neena B. Schwartz, and the valuable advice of the organizing committee contributed greatly to its scientific success. We gratefully acknowledge the funding and coordination of this meeting by Serono Symposia, USA. We also wish to acknowledge the financial contributions made by Northwestern University. We especially thank the invited speakers, poster presenters, and discussion participants who pro vided the science, interest, and enthusiasm that made this meeting on FSH a success. MARY HUNZICKER-DUNN NEENA B. SCHWARTZ vii Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv 1. An Overview of FSH Regulation and Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ULRIKE LUDERER AND NEENA B. SCHWARTZ Part I. Neuroendocrinology of FSH Secretion 2. Modulation of Gonadotropin Secretion by Proteins of the Inhibin Family: Studies in the Female Rat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 CATHERINE RIVIER AND WYLIE V ALE 3. Control of Follicle Stimulating Hormone Secretion in the Male Rhesus Monkey (Macaca mulatta) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 TONY M. PLANT 4. The Physiology of Puberty in Seasonally Breeding Birds . . . . . . . . . . . 54 BRIAN K. FOLLETT 5. Hypothalamic Regulation of FSH Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 JON E. LEVINE, LISA A. CONAGHAN, ULRIKE LUDERER, AND FRANK J. STROBL 6. Photoperiodic Control of Reproduction in Male Hamsters: Role of FSH in Early Stages of Photo stimulation . . . . . . . . . . . . . . . . . . . . . . . 83 FRED W. TUREK AND NEENA B."

The state of health care is reflected by perinatal and neonatal morbidity and mortality as well as by the frequencies of long-term neurological and developmental disorders. Many factors, some without immediately recognizable significance to childbearing and many still unknown, undoubtedly contribute beneficially or adversely to the outcome of pregnancy. Knowledge concerning the impact of such factors on the fetus and surviving infant is critical. Confounding analyses of pregnancy outcome, especially these past 2 or 3 decades, are the effects of newly undertaken invasive or inactive therapeutic approaches coupled with the advent of high technology. Many innovations have been introduced without serious efforts to evaluate their impact prospectively and objectively. The consequences of therapeutic misadventures character ized the past; it seems they have been replaced to a degree by some of the complications of applied technology. Examples abound: after overuse of oxygen was recognized to cause retrolental fibroplasia, its restriction led to an increase in both neonatal death rates and neurologic damage in surviving infants. Administration of vitamin K to prevent neonatal hemorrhagic disease, particularly when given in what we now know as excessive dosage, occasionally resulted in kernicterus. Prophy lactic sulfonamide use had a similar end result. More recent is the observation of bronchopulmonary dysplasia as a complication of re spirator therapy for hyaline membrane disease. The decade of the eighties opened with the all-time highest rate of cesarean section in the United States."

Advocating for Women with Postpartum Psychosis takes the reader into the world of one of the most misunderstood mental illnesses. Affecting 1 to 2 out of 1,000 childbearing women a year in the United States, postpartum psychosis creates hallucinations and delusions, which, if untreated, can lead to infanticide and subsequently imprisonment or death for the mother. While other parts in the world, particularly the United Kingdom have more sympathetic laws, in the United States, women with postpartum psychosis are often stigmatized as "baby killers", and face the ultimate penalty. Through this book, though, authors Feingold and Lewis humanize the mother's experience to promote understanding and compassion. Beginning with an overview of the mental health and legal facets surrounding postpartum psychosis, the authors then provide vital resources and tools for mental health practitioners and legal professionals to enact change in their practices and communities. Complete with case studies and the authors' experiences in changing the law in their own state of Illinois, this book is a necessary resource for furthering dialogue and action around maternal mental illness.

The International Women's Health Coalition was pleased to be the convenor and host of the first Christopher Tietze International Symposium, held in Berlin in September 1985. The papers in this volume represent a wide range of international views and experience with the prevention and treatment of contraceptive failure. We believe the issues discussed at the Tietze Symposium to be of interest and concern to women throughout the world and to those who would serve them. The Coalition intends to l1'ive broad distribution to this volume and encourages those interested in these issues to be in touch with the Coalition in New York City (see address below). We would like to thank The Ford Foundation, Stewart Mott, The David and Lucile Packard Foundation, the Population Crisis Committee, and The Uockefeller Foundation for their support of this Symposium. In particular we would like to express our appreciation to Sarah Lewit Tietze and Uta Landy for the devotion ann dedication which made this Symposium possible and a worthy memorial to Christopher Tietze.

The Helene Harris Memorial Trust has become recognized as providing one of the most important international fora for the presentation of research in ovarian cancer. Four biennial meetings have taken place, the most recent of which was held between May 11-14, 1993, in Toronto, Canada. This forum has grown in stature from its inception in 1987 and has brought together interdisciplinary clinical and scientific researchers from around the world who are endeavouring to perform 'cutting edge' studies in the field. The assembled group of presti gious investigators met on this occasion to present their data, to exchange ideas, and to arrange collaborations with the goal of developing new means of detection, treatment and cure of ovarian cancer. The incentive for the establishment of the Trust and its international forum was the prema ture loss through ovarian cancer of Helene Harris, the wife of Mr John Harris. Mr Harris and the Trustees looked for a meaningful way to honour the memory of Helene and to advance the noble cause of gaining an increase in the scientific knowledge of the subject. For those of us who spend most of our waking hours assisting patients and their families who are devastated by this disease, the Trust's generosity provides inspiration, hope and the opportunity for their practical application in a unique professional forum.

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.

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.

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."