Embryoimplantationisaremarkableandcomplexprocess. Approachesde- velopedfromthefieldsofcellanddevelopmentalbiology,immunology, andmolecularbiologyhavegreatlyenhancedourabilitytostudythe sharedaswellasuniquefeaturesofembryo-uterineinteractions. Impres- siveandcriticalgroundworkhasbeenlaidbyalargeanddedicatedarray ofendocrinologists,reproductivebiologists,andanatomists. Thesestudies havesetthestagetoutilizesensitiveandsophisticatedtechniquestode- tectandmodulateproteinandgeneexpression. Justasthesymbiosisofmother andfetusiscriticalforthemaintenanceofpregnancy,soisthesynergyamong investigatorsfrommanydisciplines,bothinbasicandclinicalarenas,keyto unravelingthemysteriesofimplantationandplacentation. Alargegroupof contributorsinthisfieldhadtheopportunitytomeetanddiscussthestateof thisartwiththesupportofSeronoSymposiaUSA,Inc. Whileitisneverpos- sibletobringtogethereveryonewhohasplayedanimportantrole,itwas, nonetheless,bothexcitingandgratifyingtohavesomanycolleaguestogether forthisevent. Inthechaptersthatfollow,thehighlightsofthismeetingarepresented assummarizedbytheindividualpresentersofsevendifferentsessions. The topichasbeenconsideredfromthebroadsocialandethicalimplications ofmoderninvitrofertilizationandassistedreproductivetechnologiesto detailedmolecularcontrolsovereventsthatoccurduringembryonicdevel- opment,uterinepreparationforimplantation,andplacentalorganogenesis. Thesechaptersdemonstratethesignificantandrapidprogressbeingmade inthisfieldofbiologyandmedicine. Atthesametime,theyshowthat muchmoreneedstobedonetounderstandandfullyappreciatethispro- cess. Lessonslearnedfromthiseffortcanbeexpectedtocontinuetopro- videinsightsintoother,relatedfields. Ofthemanycontributorstoour understandingoftheprocessofimplantation,nonehavehadalargerim- pactthanourcolleague,AllenEnders. Dr. Endershasplayedaparamount roleindevelopingthebasicunderstandingofthecellbiologicalprocesses vii VIII Preface underlyingimplantationandplacentationinmanyspecies,includinghu- mans. Hecontinuestocontributeandguidethoughtintheseareas. The participantsofthissymposiumrecognizedDr. Enders'impressivecontribu- tionsbyholdingthiseventinhishonor. DANIELD. CARSON * Contents Preface vii Contributors xiii PartI. Development and Future ofHuman In Vitro Fertilization and Embryo Implantation I. ImplantationintheHumanasViewedbyCanonLaw, CivilLaw,andNaturalReason 3 HOWARDW. JONES, JR. , RICHARDA. MCCORMICK, AND SUSAN L. CROCKIN 2. TheImpactofMaternalAgeandOvarianAge onImplantationEfficiency...12 STEVEN SPANDORFER AND ZEV ROSENWAKS Part II. CellularAspects ofImplantation 3. VascularInvasionDuringImplantationandPlacentation 23 ALLEN C. ENDERS AND THOMASN. BLANKENSHIP 4. OxygenRegulatesHumanCytotrophoblastProliferation, Differentiation,andInvasion:Implicationsfor EndovascularInvasioninNormalPregnancy andPreeclampsia 39 OLGA GENBACEV,YAN ZHOU, MICHAEL T. McMASTER, JOHNW. LUDLOW, CAROLINEH. DAMSKY, AND SUSAN1. FISHER 5. Embryo-MaternalInteractionsafterDiapause inaMarsupial 54 MARILYNB. RENFREE AND GEOFFREY SHAW IX x Contents 6. CellularInteractionsandtheCysteineProteinases intheProcessofMouseImplantation 67 BRUCE BABIARZ, SUZANNE AFONSO, ANDLINDA ROMAGNANO Part III. HormonalRegulation 7. NovelSteroid-RegulatedMarkersofImplantation 83 INDRANIC. BAGCHI 8. MolecularSignalinginImplantation 92 SANJOYK. DAS, BIBHASHC. PARIA, AND SUDHANSU K. DEY 9. IdentificationofProgesterone-RegulatedGenes intheUterus 107 CINDEER. FUNK, BERTW. O'MALLEY, AND FRANCESCO1. DEMAYO PartIV. MolecularMarkersofReceptivity 10. MucinsProvideaBarriertoEmbryoImplantation 123 MARYM. DESOUZA, GULNARA. SURVEYOR, XINHUI ZHOU, JoANNE JULIAN, ANDDANIELD. CARSON II. PotentialInvolvementofTrophinin,Bystin, andTastininEmbryoImplantation 132 MICHIKON. FUKUDA, DAITA NADANO,NAO SUZUKJ, AND JUN NAKAYAMA 12. OsteopontininHumanEndometrium: ARoleinEndometrialReceptivityand EmbryoImplantation? 141 CHRISTOS COUTIFARJS,AKINYINKA OMIGBODUN, PIOTR ZIOLKIEWICZ, AND JOHN HOYER PartV. TrophoblastFactors 13. TheRabbitasaModelforImplantation: InVivoandInVitroStudies 151 LORENH. HOFFMAN,D. RACHEL BREINAN, AND GARETHL. BLAEUER 14. RegulationofTrophoblastEndocrineFunction: ThePlacentaDoesItsOwnThingTranscriptionally...161 JEROMEF. STRAUSSIII ANDLEE-CHUANKAo Contents XI 15. TranscriptionFactorsRegulatingtheDifferentiation oftheTrophoblastCellLineage 167 IANC. SCOTTANDJAMESC.

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

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 practice of clinical reproductive medicine has practice in the era of managed care and coordinat gradually moved from its initial 1980-90 hospital ing ancillary offsite medical personnel. base to its present (circa 2001) office site of oper The objective of this text is to assist in this ongo ation. With this transition have been improvements ing endeavor by presenting in a clear, concise man in efficiency of practice often in response to ner many of the topics relevant to contemporary increased pressure to provide the most patient sat office-based infertility practice. The initial half of isfaction. An added challenge of office-based prac this text addresses topics which focus upon general tice has been taking on many of the responsibili concepts of infertility evaluation and practice. The ties of what had been traditionally the hospital's latter half is a practical approach to the execution domain. Some of these new responsibilities have of specific office-based infertility procedures. We included the ordering of operative supplies and hope this book will assist all medical personnel who equipment, the establishment of quality control dedicate their clinical effort in achieving what is programs, construction and maintenance of special most coveted by our patients, the birth of a healthy laboratory spaces, redesigning efficient methods of newborn. DAVID B. SEIFER, M. D. UMDNJ-Robert Wood Johnson Medical School ROBERT L. COLLINS, M. D. The Reproductive Center, Youngstown, Ohio October 2001 vii Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi . . . . . . . . . . . . . . . . . 1 Evaluation of the Female for Infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bryan D."

Recent years have seen tremendous progress in the field of hormone action and consequent signal transduction. The 40th Colloquium Mosbach was devoted to the discussion of results concerning the molecular process of hormone action, especially the processes following hormone binding to the corresponding receptors. Structural and functional aspects of steroid hormone receptors as well as ion-channel-coupled and enzyme-linked receptors were treated in detail. Particular interest focussed on the latest results concerning transcriptional control, protein phosphorylation, the role of G-Proteins, oncogene proteins, involvement of phospholipases and the regulation of ion channels.

The methods of molecular biology, biochemistry, immunocytochem istry, and in-situ hybridization introduce new opportunities for the classification and functional characterization of cell receptors under normal conditions and for a better understanding of pathogenetic mechanisms in human diseases. The cellular localization and trans location of receptor proteins can be identified using morphological methods, and it is apparent that receptors and receptor defects play an important role in pathology, notably in genetic diseases, endocrine disorders, atherosclerosis, infections, and cancer. In this volume in ternational experts give a current review of the morphology and pathological aspects of cell receptors. The complex communication of multicellular organisms is coordi nated by two regulatory systems: neural and humoral. Both systems function via signaling substances (ligands) and signal-recognizing and -transmitting molecules, called receptors. The historical develop ment of the receptor concept is based upon Paul Ehrlich's theory of "receptors in the immune system," Langley's "receptive substances in postssynaptic membranes," and Earl Sutherland's discovery of "sec ond messengers" (cAMP and Ca2])."

The media now regularly feature breakthroughs on the influence of prenatal hormones on the brain and behavior, for instance the link to financial performance or risk management. Based on these findings and their own experiments, the authors present the Hormonal Quotient (HQ) as a scientific, holistic and reliable career management and personal development tool for professionals. Eight HQ profiles and their corresponding typical business skills and preferences are presented and enable the reader to benchmark their HQ with peers, design an ideal career plan, build a winning team in business and find the perfect work-life balance. A complimentary website allows readers to easily measure their HQ online.

By the author of "The Right Sensory Mix," Berry-AMA Book Prize Finalist 2011 - one of the four best marketing books in 2011 according to the American Marketing Association Foundation.

The Berry-AMA Book Prize is awarded annually be the American Marketing Association Foundation (AMAF) and recognizes books whose innovative ideas have had significant impact on marketing and related fields.

Diabetes mellitus represents one of the most frequent and serious clinical syn dromes in contemporary medicine. Since the end of the nineteenth century, the endocrine pancreas has been implicated in the pathogenesis of this disease. Several pathologists of the twentieth century detected various lesions and mor phologic alterations in the pancreatic islets of diabetic patients, but the patho physiologic basis of their findings remained long obscure. The systematic mi croscopic work of WILLY GEPTS clarified the views and related the variety in histopathology to differences in origin, duration and clinical expression of the disease. Over the past two decades, the concept of a multifactorial origin of diabetes has become widely accepted. Various agents and mechanisms have been identified which can lead to a quantitative or qualitative deficit in pancre atic B-cells. The purpose of this book is to bring an update on the many path ways which may induce an absolute or relative insufficiency in insulin release and hence a diabetic state. Rather than bringing a complete account on all re search relevant to the understanding of the pathology of the diabetic pancreas, the authors of the various chapters of this volume have focussed on selected processes which can impair B-cell function, survival or regeneration.

The Organon Symposia have actually become a tradition, keeping up with exciting developments in reproductive medicine. The purpose of this symposium on "Fertiliza tion of the Human Egg in Vitro" was to bring together the stilllimited number of elinical specialists in the field and to stimulate another group of basic research people to exchange their experiences and knowledge, hopefully promoting elose cooperation between the two groups. It was a kind of scientific "first" that all research teams so far successful in achieving the birth of a healthy baby, fertilized in vitro came together at a workshop conference without a large audience of spectators and reporters, but with a small number of highly critical colleagues from the fields of basic reproductive physiology and comparative developmental biology. This atmosphere allowed for the elose exchange of results, hypotheses, diagnostic and therapeutic procedures, criticism, and respect, and created very productive discussions, all of which furthered the aim of the method: To help more childless couples to have their own babies by the ultima ratio procedure of in vitro fertilization and embryo replacement. The book that has emerged from this symposium will help to disseminate the great amount of information and experience gathered among the scientifically and clinically interested colleagues of many other hospitals and universities who could not be invited to the meeting. At the same time, it will prove that there is much more work to be done in the basic and clinical sciences of human embryology and reproductive biology."

The sellar region and paranasal sinuses constitute the anatomical sections of the skull base in which pathological entities warrant interdisciplinary management. Processes originating in the paranasal sinuses can reach and involve the skull base in and around the sella, sometimes not respecting the natural dural boundary. On the other hand, lesions involving the sellar block, such as pituitary adenomas and meningiomas, can also extend downwards into the paranasal sinuses. The orbit and cavernous sinus may be subject to involvement and infiltration by both paranasal and sellar pathology. The advancement and new achievements of modern diagnostic procedures, such as high-resolution CT, three-dimensional reconstruc tion, MRI, and MRI angiography, as well as the detailed selective angiographic protocols and endovascular techniques, have increased the possibilities for surgical management of this type of pathology with extra- and intracranial involvement. Long-standing and intense inter disciplinary work has led to sophisticated operative approaches which for benign tumors allow total excision with preservation of structures and function, and for some malignant lesions permit an en bloc resec tion via a combined intracranial-extracranial approach. This volume reflects the work and scientific exchange which took place during the IV International Congress of the Skull Base Study Group, held in Hanover. Leading authorities in the basic sciences including anatomy joined with diagnosticians, clinicians, and surgeons from different fields to evaluate the state of the art of this topic in skull base surgery."

"When a thing ceases to be a subject of controversy, it ceases to be a subject of interest. " WILLIAM HAZLITT (1778-1830) This is the fourth volume in a series which we started in 1997. In 1976, Varco and Delaney edited a "surgical bestseller" entitled Controversy in Surgery. This was fol lowed by a second volume in 1985. The immense success of these books among both surgical trainees and experienced surgeons, and their wide international ap peal, supported the editors' notion that a view of controversy is integral to teach ing. However, despite major advances in surgical science and practice, no other similar publication has since been put together with the objective of addressing major controversies in surgery. The aim of this series is to address such deficiency by covering the most crucial current controversies in general, vascular and trauma surgery. Since almost everything is controversial in surgery, we will be able to tackle different issues almost each year. The editors have selected a nationally/internationally recognized authority for each topic. Most books available today are either "North American: ' "British-Com monwealth" or "British-European: ' contributing to the constant transatlantic rival ry. Our series specifically aims to bridge this "culture gap" and includes North American, British, European, and other authors while maintaining a cohesive structure. This will hopefully also broaden the appeal of such a book across both sides of the Atlantic and beyond."

The growth and function of many tissues are influenced by hormones. Therefore it is quite understandable that hormones play a role in the development and treatment of malignant tumors. Numerous publications address this topic; however, the results of many studies are controversial and have not been unequivocally accepted. For nearly 50 years the carcinogenic effect of steroid hormones has been under debate, and their therapeutic value a matter of discussion for equally as long. The present volume concentrates on substantiated data first obtained from the study of tumors developing from hormone regulated or hormone-producing tissue, e.g., the thyroid, adrenal glands, prostate, and the female genital tract. Through a joint approach from the field of molecular biology, biochemistry, and histopathology, advances in the management of these tumors have been elaborated. Another exciting example is the endo nuclear diagnosis of adrenal tumors. Antihormones, i.e. antian drogens or GnRH analogues have proved to be important indeed since they exhibit a destructive effect on prostate carcinomas and breast cancer. Further improvements can be expected in the localization of hormones in tumor tissue by specific antibodies. A special chapter is dedicated to the diffuse endocrine cell system (DECS), the clinical significance of which has mainly become obvious in the gastroenteropancreatic tract.

The authors of this book have a goal-to describe the management of infertility from the perspective of physiology and anatomy gone awry. To accomplish this goal, the chapters devoted to the causes of infertil ity begin with a description of the normal structure and function of the organ or system causing the infertility. We believe that under standing the normal will result in rational and effective diagnosis and treatment of infertility. Our intent is that this book be a useful re source for those who care for infertile couples. For an infertile couple, success is the delivery of a normal and healthy infant. Chapters that describe the causes and treatment of habitual abortion and the reproductive performance of previously infertile couples emphasize the hazards that exist between conception and birth. Our environment is one of these hazards, one that may also affect reproduction before conception. A chapter is devoted to a de scription of environmental agents that affect reproduction, the mech anisms of their effect, and methods to predict those present and future environmental agents which might also affect reproduction."

Die Beitrage dieses Buches beschaftigen sich mit Autoimmunitat, Immuntherapie des Typ-I Diabetes, Virusgenese, Insulintherapie und -allergie. Schwerpunkte liegen auf den dynamischen Aspekten der Insulinsubstitution unter Berucksichtigung einer angepassten Diat und der Therapie mit oralen Antibiotika, Insulinen und Pro-Insulinen. Gleichzeitig wird anhand der Makro-Angiopathie und der Neuropathie auf die Auswirkungen der dynamischen Insulinsubstitution bei Sekundarkomplikationen hingewiesen. Die Moglichkeit der computerunterstutzten Therapiefuhrung und glukosesensorgesteuerten Biofeedback-Kontrolle werden vorgestellt. Ein umfangreiches Kapitel vermittelt den aktuellen Stand der experimentellen Forschung und der klinischen Anwendung der Pankreas- und Inselzelltransplantation.

In the last decade, it has become increasingly evident that the clini- cal and morphologic changes underlying many of the complications of diabetes, including cataract formation, retinopathy, nephropathy, neuropathy, and macrovascular disease, are preceded by a variety of disturbances of biochemical and physiologic origin. Dr. Cohen has recently written a superb monograph, entitled Diabetes and Protein Glycosylation: Measurement and Biologic Relevance, in which she thoroughly explores how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for main- tenance of long-term euglycemia. In the present volume, The Polyol Paradigm and Complications of Diabetes, she reviews, in a most succinct and thorough manner, how another biochemical mechan- ism, involving the polyol pathway, is involved in the pathogenesis of such diabetes complications as retinopathy, neuropathy, nephropa- thy, and cataract formation. Dr. Cohen gives us a clearly written and comprehensive mono- graph, reviewing the chemistry of the polyol pathway and of the aldose reductase inhibitors, and the pathophysiologic significance of increased polyol pathway activity in a variety of tissues affected by Vlll Foreword diabetes mellitus. She insightfully describes the relationship of increased polyol pathway activity to altered metabolism of inositol- containing phospholipids and to changes in various tissue concentra- tions of myo-inositol. Finally, she provides us with a careful review of the existing experimental and clinical studies with a variety of different aldose reductase inhibitors that have been and are being performed in the hope of preventing or reversing long-term compli- cations of diabetes.

One of the hallmarks of aging is the decreased capacity to adapt to changes in the environment. In a constant, controlled environment, it is often difficult to distin guish the functioning of the young organism from that of the old. However, when stresses are applied-temperature stresses, dietary stresses, infection, emotional stresses-the differences are more apparent. Frequently, the response ofthe old is delayed and may never reach the same mag'nitude as the young. These responses, in most cases, are mediated by the neuroendocrine system, which communicates via hormones, neurotransmitters, and related substances. Thus, it is important to understand the age-related changes that take place in the secretion and act ion of these substances and how these changes relate to the well-being of the whole organism. Indeed, the "neuroendocrine theory of aging" proposes that almost all of the characteristics of aging can be accounted for by dysfunction of the neuroendocrine system. A book on endocrine function and aging is particularly relevant at this time. With the advent of the techniques of molecular biology, there has bee an explo sion of knowledge concerning hormone secretion and action. Hormones, pro hormones, hormone receptors, and "second messenger" mediators rapidly are being cloned and sequenced. Such knowledge gives us important insights into the molecular workings of these substances as well as into the genetic hasis of endo crine dysfunction. These new tools are now being applied to the problem of age related changes in endocrine function."

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.

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper- function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self- constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

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.

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.

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."

This volume is the product of a symposium held on 14-16 February, 1985 in Ham- burg in honour of the 65th birthday of Prof. Hans-Joachim Schumann. Schumann was born on 28 December, 1919 in Stralsund. He studied medicine in Cologne, Greifswald and Rostock. The chair of pharmacology in Rostock was held at that time by Peter Holtz. It was he who first introduced Schumann to pharma- cology in 1944 and who was his Doktorvater (research supervisor). Mter the war, Schumann again worked with Holtz in Rostock and then in Frankfurt am Main. He received decisive stimuli during a research fellowship, in 1956, in Prof. J. H. Burn's department in Oxford, where he also worked with Prof. H. Blaschko. In 1964 he ac- cepted his present position as ordentlicher (full) Professor and Head of the Institute of Pharmacology and Toxicology of the then newly founded Medical Faculty of Es- sen. He has remained in Essen despite being offered the chair of pharmacology in G6ttingen in 1968. It is interesting to observe how in the main lines of his scientific work, which now spans 40 years, Schumann has followed the steps involved in autonomic neuro- transmission from transmitter release to transmitter-receptor interaction.

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.

Publication of this monograph acknowledges great strides made in research on the zona pellucida during the past decade or so. The body of work presented testifies to a resurgence of interest in the zona pellucida, prompted largely by a renewed appreciation of its unique properties and its important functions during early mam malian development. It is gratifying to realize that the zona pellucida has at last achieved a well-deserved attention. Whereas extracellular coats of nonmammalian eggs have been studied intensively for many years, the zona pellucida by comparison, has until now taken a back seat. Fortunately, the research presented here signals an end to this situ ation. Many of the difficulties inherent in working with relatively small amounts of material have been overcome, paving the way for application of a wider variety of experimental approaches to the zona pellucida by a larger community of investigators. Hopefully, this monograph will serve as a catalyst in this regard. As revealed in these pages, application of contemporary experi mental methodologies has had significant impact on both pure and applied research on the zona pellucida. For example, modem im munological approaches have been used to assess molecular fea tures of zona pellucida structure and function, as well as to evalu ate the zona pellucida as a potential contraceptive target antigen."

The "Handbook on Parathyroid Diseases" presents a comprehensive and concise overview of our current knowledge in the area of parathyroid function, hormone regulation and disease states.

The Handbook educates the reader using a case-based approach presenting current evidence in the field. The material is presented in an easy to read and understandable language and uses a plethora of tables and text boxes where possible. Complex concepts are conveyed in simple and clear language. Leading international experts contribute to this state of the art book providing a true depth of knowledge and practicality.