This volume summarizes the proceedings of the fifth biennial Cancer Teaching Symposium held on March 4 and 5, 1972 at the University of Chicago Pritzker School of Medicine. The program was prepared by Drs. MELVIN GRIEM, ELWOOD JENSEN, HAROLD SUTTON, JOHN ULTMANN, and ROBERT WISSLER. The purpose of the symposium was to present the current status of the challenging cancer problem, breast carcinoma, to the staff and students of this medical center and to students and in terested physicians from other institutions in the Chicago area. In a fashion similar to the other teaching symposia held in 1964, 1966, 1968, . and 1970, this symposium attracted over 450 physicians and scientists. In the course of one and one half days the audience had the opportunity to listen to 18 invited speakers and to the lively discussions. The formal presentations are recorded in these pages. This teaching symposium could not have been undertaken without the faithful assistance of the program committee, the cancer training grant education committee, the staff who recorded and transcribed the proceedings, and the editorial assistants. We wish to thank the following for their efforts: JULIE KANT, Administrative Secre tary for the Clinical Cancer Training Grant, as well as Dr. JAMES MARKS, MARGARET WOEHRLE, FRIEDA RANNEY, and ROSIE BARTLETT. This symposium received financial support from USPHS Clinical Cancer Train ing Grant 5T12 CA-08077-06 and from the Chicago Tumor Institute. MELVIN L. GRIEM, M. D. ROBERT W. WISSLER, Ph. D., M. D."

This title includes a number of Open Access chapters. Nutrition is not only a basic need that all humans have to sustain life, but it is also critical to successful early development. This research compendium lends deeper insights into the links between nutrition and healthy brain function-and from the reverse perspective, between nutrition and neurocognitive disorders. This well-organized and accessible compendium offers a vital research context for policymakers, educators, medical providers, and families. It underlines our urgent responsibility to give children a strong start by improving prenatal and early childhood nutrition.

Care for Children Born Small for Gestational Age is a comprehensive handbook that serves to synthesize the extensive recent literature in the area to provide a practical resource aimed at a wide range of healthcare professionals, including obstetricians, midwives, neonatologists, and primary care physicians. This comprehensive handbook includes an in-depth survey of the prevention, diagnosis, treatment and long-term monitoring of children born small for gestational age, as well as related conditions such as intrauterine growth restriction, metabolic syndrome and type 2 diabetes. Additionally, the short and long-term psychiatric and social consequences of this condition are addressed.

A synopsis of the use of lasers in gynecology is presented in this book; it is supported by more than 10 years of experience and backed up by studies inthe fields of experimental surgery, technical medicine and clinical gynecology. The authors show how laser-assisted preparation hasbroadened the spectrum of operative possibilities in gynecology. Major points of attention are experimental surgery and basic research, details of application with respect to specific indications, and future potential. Furthermore, the clear definition of the possibilities and limitations of laser technology puts an end to the highly stylized view of a patent wonder divorced from general operative standards. Thereis no doubt that users of laser technology stand on the threshold of a promising development and yet, despite the present elegant applications, thefirst steps to maturity are only now being taken.

This concise, truncated version of Nagy, Varghese and Agarwal's Practical Manual of In Vitro Fertilization is comprised of select clinical chapters for a portable, affordable and up-to-date resource. Gamete Assessment, Selection and Micromanipulation in ART covers a variety of topics, including: - Human oocyte evaluation - Sperm evaluation and selection - Micromanipulators and micromanipulation - Biopsy procedures on oocytes and embryos - Molecular insights in IVF Practical for both clinicians and researchers alike, Gamete Assessment, Selection and Micromanipulation in ART brings together all of the need-to-know information about these important topics in reproductive medicine.

It is in the surgical aspect of their specialty that the gynecologists' work may be most frequently judged by their peers or by the litigious society that currently exists. Great and commendable progress has been made over the past 30 years in the basic scientific, endocrinologic and obstetric aspects of the specialty, but this has occurred with a commen surate de-emphasis of surgical procedures and surgical training, a decline in devotion to technical detail and perfection, and a tendency to take surgery for granted. Obstetric and gynecologic residency programs provide increasing numbers of specialists with average competence in the performance of the common, rather standardized gynecologic operations. In general, technical skill in the extirpative operations can be acquired far more readily than proficiency in the art of reconstructive surgery. At present, for a number of reasons, gynecologic surgical training is most deficient in regard to the surgical correction of severe forms of obstetrically damaged genital tract supports. The operations for pro lapse defy standardization and require great technical individualization; this must be based on the surgeon's judgment developed through expe rience, a thorough understanding of normal pelvic anatomy, and recog nition of the deficiency responsible for the prolapse in individual cases.

The mechanisms that initiate labour (i. e., the conversion of the quies cent uterus to an active and reactive organ at term) are poorly under stood. Of considerable importance are the factors that control preterm labour and preterm birth, with their devastating effects on society. This problem is the leading obstetrical issue. Preterm labour affects ap proximately 10% of all pregnant women (even higher numbers are re- Abb. I. The participants of the workshop VI Preface ported for less developed countries or where prenatal healthcare is a low priority) and it is the leading cause of morbidity and mortality of babies. Current practices to arrest preterm labour, once initiated, are in effective. In addition, procedures to stimulate labour and dilate the cer vix at term may not be used effectively. On October 19th - 21 st, 1992, a Schering Foundation Workshop took place in Berlin to discuss the "Basic Mechanisms Controlling Term and Preterm Labour." Leading scientists from Europe and North America were assembled to consider the fundamental systems which regulate the uterus and cervix during pregnancy. The topics in the sym posium ranged from key cellular events governing uterine contractility and cervical dilatation during labour to clinical advances and applica tions. This book contains the proceedings of the workshop. We were pleased to have been part of the workshop and to have been responsible for its organization."

Sixteen British specialists pool their extensive knowledge of spontaneous abortion in one source. Their discussion is directly applicable to clinical situations and helps identify areas of debate and alternative methods.

Many women have to spend one third of their lives in a postmenopausal state and they should have a good quality of life during this period. Althoug HRT is well accepted as the logical treatment of climacteric problems, the prevalence rate is very low in some countries. The reasons for not accepting HRT are manifold and complex. The objective of this book is to describe the essential advances in basic and clinical research that forms the basis of current HRT and to give an overview of the efficacy and safety of HRT.

The events of September 11,2001 in the United States will always be r~membered with horror and sadness but also admiration for those who risked, and often lost, their lives attempting to save others. When the Fifth International Germ Cell Tumour Conference began, the US air space was closed and our American friends were unable to join us. We were faced with a programme that now had many gaps. What happened next was an illustration of the sense of community that prevails at the Germ Cell Tumour Conferences. Some of those who could not be there in person, such as Richard Foster and Craig Nichols, sent their slides by email, and we were indebted to those, such as Michael Jewett, Ben Mead and Malcolm Mason, who stepped into the breach to present them. Others gave impromptu, and often thought provoking, talks. The discussion periods were lively and it will come as no surprise to those who regularly attend the meeting that Tim Oliver won the prize for "Most Questions Asked", managing even to ask questions following his own presentations. The quality of the talks was outstanding. There was closer integration of the adult and paediatric sessions than in previous meetings. As a result, the differences and similarities between adult male, female and paediatric germ cell tumours became more apparent. This cross-fertilization of ideas from different groups will no doubt lead to further advances. As a result of all these efforts, the conference was a great success.

The introduction of colposcopy and exfoliative cytology as a means of examining the cervix uteri has opened up the possibility of studying the preceding and early stages of invasive carcinoma of the cervix and has also brought to light a number of conditions which are possibly only indirectly related, if related at all, to cervical neo with histological evaluation it is possible to plasia. Using these methods combined gain some insight into the natural history of cervical carcinoma. The importance of this is not confined to the cervix for, in this respect, the cervical lesions may prove a paradigm for those of the bladder, stomach and elsewhere. At present the broad outline of the natural history of these cervical lesions is emerging but the temporal and spatial relationships of the various phases is unclear, largely because of the number of possibilities envisaged which involves more vari ables than can be controlled in anyone investigation. In this monograph we have endeavoured to indicate the limitations of the various approaches and to stress the need for controlling the accuracy of assessment whether it be histological, cytological or colposcopic."

Progesterone, the hormone "pro gestationem", plays a pivotal role in mammalian reproduction during almost all phases of the menstrual cyc1e and all stages of pregnancy. It is involved in the control of ovula- tion, prepares the endometrium for implantation, and, in later stages of pregnancy, is responsible for its maintenance by suppressing uterine contractility. The sudden withdrawal of progesterone action at the end of the nonfertile cycle leads to the constriction of spiral arteries and, in . turn, to menstruation in human beings and non human primates. The decrease in serum progesterone concentrations or its functional with- drawal in the myometrium and decidua are the most important events during parturition in various mammals. In the uterus, progesterone controls the growth and differentiation of endometrial and myometrial cells and regulates a variety of cell functions directly by either stimulating or inhibiting structural and functional proteins, but also indirectly by functionally opposing estra- diol action. In the nonpregnant uterus, there are different progesterone effects on uterine cell proliferation which vary among species. In the fertile cyc1e, progesterone regulates in synergism with estradiol the transport of the fertilized eggs and the c1eavage stage embryos through the oviduct and induces the secretory changes in the endometrium re- quired for implantation. During the period between ovulation and im- plantation, remarkable morphological and biochemical changes in the lumenal and glandular epithelial cells take pi ace under the influence of rising progesterone levels in the human and primate endometrium.

This book is a collection of preclinical and clinical reports on the appli cation of gene therapy to human disease. The focus of these studies is on cancer and cardiovascular disease. There are two fundamental technologies for delivering therapeutic genes to diseased ceHs: either viral vectors, as discussed by Dr. Bal main, or non-viral vector systems, as discussed by Dr. Felgner. The strengths and limitations of each of these delivery systems are charac terized. The use of a therapeutic gene to treat a disease has taken two general approaches. The first is to introduce anormal (i. e., wild type) gene into the patient that will restore normal gene function. Dr. Weiss man has characterized the tumor suppressor gene (pS3), and has shown that it can restore normal ceH function in cancer cells. The second ap proach is to treat the disease with antisense molecules. Abnormal gene expression can be down-regulated and selectively inhibited by anti sense molecules, which can reverse the pathologie process in cancer cells. Dr. Gewirtz has demonstrated this with anti sense genes on leuke mia, while Dr. Scanlon has applied this principle using ribozymes in human carcinomas. During this symposium, Dr. Engler described clinical studies of gene therapy using growth factors to stimulate new blood vessels in patients with cardiovascular disease. Several gene therapy strategies were used for cancer: overcoming drug resistance by Dr. Bertino, a pro-drug strategy with ganciclovir by Dr."

Professor Egon Diczfalusy, a pioneer in gynaecological endocrinology and in particular female contraception, celebrated his 80th birthday with a scientific symposium. The participants were scientists from all over the world who had been scholars and close collaborators at different points in time. The interdisciplinary meeting consisted of lectures on the epidemiological impacts of ageing, its challenge for the pharmaceutical industry, philosophical aspects of the future of mankind, and the history and future of contraception. Three round table discussions addressed the hormonal control of reproduction and ageing, new approaches and future perspectives of contraception for women and men, and hormone replacement in the elderly.

The study of prenatal development provides many clues for understanding the physiology as well as the pathogeny of malformations and many diseases. I became interested in the analysis of human development as a young medical student more than 30 years ago, and I have stayed in this field all my life. In my studies, I always tried to compare the events of different disciplines such as genetics, anatomy, bio chemistry and physiology. I learned that the development of a structure is, under normal circumstances, strictly determined and that the development of structures always precedes their proper function. There are no changes in function without changes in structure. The life of every cell is genetically preprogrammed and the program may be modified by complicated interactions with environment. Recent progress in our knowledge is basicly related to technology. However, using all the tools of today's technology, we are still unable to understand the basic normal development. After almost thirty years of work, I am trying to present a subjective review of the development of the human endocrine glands. I am presenting an image emerging from my experience. I personally studied several hundred human embryos using mostly anatomical, histochemical and some biochemical techniques. I found much additional information in the literature."

The optimal function of the placenta and thus fetal well being largely depends upon the integrity of both the fetal and maternal circulations of the placenta. Intense basic research concerned with placental vascularization and blood flow has been performed for the past 30 years, beginning with the classical morphological descriptions of the placental vessels by Boe (1953) and Arts (1961), as well as with the radioangiographic studies of maternal placental circulation in the human by Borell (1958) and in the rhesus monkey by Ramsey (1962). The scientific framework presented by these investigators has been filled and completed by numerous investigators, leading to more morphological details, functional considerations, and pathological understanding. For an extended period of time, this research has been of primarily academic interest by increasing our insights into one important system of the placenta, yet having nearly no practical importance. Recently, this situation has changed dramatically: in vitro studies of the isolated, dually perfused human placenta and in vivo studies of placental circulation for diagnostic purposes have raised an enormous interest in basic research data. New methods like Doppler Ultrasound and NMR became available. These technics have enabled the obstetrician to study fetal and placental hemodynamics in vivo. Meanwhile, such methods are becoming incorporated into the daily obstetrical routine, to some degree without an adequate background knowledge of placental vascularization and blood flow, since such experience is currently available to only a small group of experts.

Based on the current edition of the bestselling Gabbe's Obstetrics: Normal and Problem Pregnancies, this new study guide is a useful resource for self-assessment and increasing your understanding of major concepts in the field, as well as a practical review tool for exam preparation. Gabbe's Obstetrics Study Guide contains nearly 650 questions and answers that cover the information you need to know, in a format that mimics the board exam and prepares you for the next steps in your education and your career. Includes short-form and vignette-style questions to fully prepare you for what you'll see on exams, as well as rationales for correct and incorrect answers and interactive self-assessment online. Offers teaching points with each question to help you identify core concepts and ensure that you thoroughly understand the material. Features nearly 1,000 full-color photos, line drawings, ultrasound images, and tables drawn from the parent text. Provides links to the parent text so you can quickly access a full review of relevant concepts, plus up-to-date reference at the end of each chapter for further reading. Expert ConsultT eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, and references from the book on a variety of devices.

Operative Gynecologic Endoscopy, Second Edition is completely revised and expanded with 17 new chapters that provide, step-by-step, the latest operative techniques for both laparoscopic AND hysteroscopic procedures. New and updated chapters include: - laparoscopic assisted vaginal hysterectomy - vaginal prolapse and bladder suspension - ectopic pregnancy - tubal reconstructive surgery - assisted reproductive technologies - lymphadenectomy and urologic procedures - operative hysteroscopy. In addition, this volume includes comprehensive chapters on instrumentation, photo documentation, anesthesia, operating room personnel, credentialing, and legal issues. More than 350 superb illustrations - with many in full color - complement and clarify the operative techniques. For every surgeon and resident performing gynecologic procedures, this is the definitive, most up-to-date text on gynecologic endoscopy.

Reproduction is, it would appear, a very simple biological event: the result of an act of love. In actual fact, it has always been, and still continues to be, one of the most complex, yet at the same time, most fascinating, problems, with which Science has ever been engaged. Physiopathology of human reproduction has always made use of investigations of a morphological nature, perhaps on account of the need to "see inside" the reproductive apparatus or within the gonads themselves in order to better understand how they function. Observation of spermatozoa practically coincided with the discovery of the microscope, and histological study of the testis and ovary was, for a very long time, the only means available with which to closely follow the evolution of gametes destined to their meeting. Improvement of techniques resulting from the evolution of endocrinology of reproduction has only apparently put aside morphological techniques, whilst at the same time there has been a gradual development of ultrastructural techniques, on the one hand, and, on the other, macroscopic diagnostic systems through images.

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 body of any animal can be viewed as a society or ecosystem whose individual members are cells, reproducing by cell division and organized into collaborative assemblies or tissues. In this ecosystem, the cells are born, live and die under various forms of selection pressure such as territorial limitation, population size, source of nutrients provided, infectious agents, etc. The body is a highly organized society of cells whose main task is the maintenance of homeostasis of the whole organism. The failure of control mechanisms which make the cell the unit of society, marking the beginning of its asocial behaviour, is most frequently a malignant alteration. This process is not abrupt, nor is it based on a single event. It is, rather, a long-term process characterized mainly by mutation, competition and natural selection operating within the population of cells. The basic mechanisms controlling the cell sociability represent the first defence line against the altered cells, while the second line of defence is supposed to be made up of the immune system cells.Speaking in Darwinian terms, within the ecosystem of an organism, cells of the immune system operate as predators of the altered and mutated cells or cells infected by the intracellular parasites. The biological phenomena whose mechanisms are, at present, explored and largely understood, certainly had their own evolution. Searching for the origin and details of the evolution of advanced solutions as well as selection pressures that might justify their emergence and existence, we often fail to see that many such phenomena are, in fact, co-evolutionary by-products of evolutionary innovations. In other words, the evolutionary emergence of advanced solutions is sometimes, if not always, accompanied by certain by-products and by the co-evolution of compensatory mechanisms acting as a counterbalance to these. An example of the evolution of advanced solutions is the evolution of adoptive immunity, and co-evolution of auto-immunity and alloimmunity. Alongside the diversification of the mechanisms of adoptive immunity, auto-immunity and alloimmunity gain attributes of the evolutionary by-products and become sources of selection pressure.To that effect, alloimmunity could be a source of very strong selection pressure in mammals, simply because it is directly connected with the reproductive efficacy. At the same time, new forms of selection pressure that are connected with adoptive immunity gave rise to new mechanisms controlling killer machinery of the immune system. Finally, the last in a line of by-products in the processes of evolutionary modelling and re-modelling of vertebrate immune systems can be regarded as the failure of anti-tumor immunity. There is now much evidence that tumors can be immunogenic. Tumor cells very often express antigens in a form recognizable by the host immune system, but most frequently without consequences on tumor progression. This has been shown in many experimental models and different experimental conditions. Immediate mechanisms for the escape of tumors from the immune response are very similar to mechanisms for the escape of the fetoplacental unit (as allograft) from the maternal immune response. The similarity between these two mechanisms is so significant that any randomness must be banished.Mechanisms of anti-tumor immunity in mammals are probably substantially different from mechanisms of anti-tumor immunity in other classes of vertebrates. Moreover, the type of most frequent tumors in non-mammalian vertebrates is also significantly different. Finally, the incidence of malignant tumors in non-mammalian vertebrates is significantly lower than the incidence of malignant tumors in mammals. These facts indicate that the mammalian immune system during the anti-tumor immune response is tricked by the similarity between tumor cells and trophoblast or other placental cells. From this aspect, anti-tumor immunity failure in mammals can be defined as an immunoreproductive phenomenon, which is developed under the evolutionary pressure of auto-immunity and alloimmunity/reproductive effectiveness. It may be a specific evolutionary approach in the rendering of anti-tumor immunity failure in mammals, and a new possibility for anti-tumor immunotherapy.

Almost every aspect of energy and nutrient metabolism is altered by hormonal and other physiological changes during pregnancy and lactation. While it is evident that hormonal adjustments affect nutrient requirements, these are rarely considered when nutrient recommen dations are made for pregnant or lactating women, and often neglected during evaluation of nutritional status. In addition, changes in nutrient metabolism during the stages of pregnancy and oflactation are usually considered separately, while in reality events during pregnancy can have a major influence on nutritional status and nutrient requirements during lactation. The purpose of this volume is to describe changes in the metabolism of important nutrients during pregnancy and lactation, including the physiological basis for these changes and their implications for nutrient requirements and assessment. Authors have considered such issues as inter-relationships between endocrine changes and nutrient metabolism at the tissue, cellular and molecular level; alterations in nutrient binding proteins; the efficiency of nutrient absorp tion and retention; and the impact on maternal as well as fetal nutritional status. Another unique aspect of this book is the focus on pregnancy and lactation as a continuum."

For out of olde hokes, in good feyth, Cometh all this newe science that men lere. Geoffrey Chaucer The Parliament of Fowls During the past two decades knowledge of the human menstrual cycle and of normal and abnormal reproduc- tive function has increased at a dramatic rate. As rec- ognized in this volume, this explosion of knowledge is due in large measure to the development of radio- immunoassays for the measurement of the minute quantities of reproductive hormones found in the cir- culation. Yet the foundations for the many recent developments were laid well in advance. The concepts and hypotheses tested were often suggested even be- fore the hormones involved were identified and iso- lated. A consideration of the historic aspects of re- search in this field places recent research in the appropriate perspective. Moreover, as presented by Drs. vii viii FOREWORD Gruhn and Kazer, the history of progress in this field makes fascinating reading. A review of the history of reproductive endocri- nology should be required reading for all students of the subject and reproductive endocrinologists in train- ing. Dr. Griff T. Ross, a noted reproductive endocri- nologist, often instructed his students that every hy- pothesis he tested could be found in some form in the publications of previous scientists. The answers to present and future questions are often hidden in the lessons of the past.