Can the art of predictive medicine anticipate the development of diabetes? And if so, what can be done about it? How early is early enough to intervene effectively? With what therapeutic modality? Why? Big babies are not an infrequent occurrence in mothers with normal carbohydrate metabolism for another 10, 20, or even 30 years. The abnor- mality present during pregnancy is now accepted as what is inherited with the diabetic predisposition, or what can be recognized as the diabetic susceptibility. It occurs before hyperglycemia, during the phase of dy- namic resistance to diabetes, during the prediabetic period. Prediabetes means before diabetes, and was applied for the first time by Mara~on in Spain, to signify the stage before hyperglycemia. Foglia in Argentina used the term in 1944 for his pancreatectomized rats. We pub- lished the first paper on humans in 1951 (Camerini-Davalos, R.A., Landabure, P., and Serantes, N., Rev Med Cordoba 39: 187).

Endocrine conditions requiring surgical intervention in the pediatric age group are uncommon. When diagnosed, they are the source of great in terest and, often, considerable debate. This is understandable, since few centers and even fewer individual surgeons can draw on vast experience of this subject. The great divergence of opinion regarding management is also understandable in that pediatric endocrine lesions often differ considerably from their adult counterparts in histology, natural history and response to treatment. Pediatric endocrine lesions are also, as a rule, less frequently malignant. In addition to the great strides made in surgical and anesthetic technique and operative monitoring, progress in four areas has substantially advanced the management of endocrine dis orders in the pediatric age group in the last decade: imaging, pathology, pharmacology and genetics. The new imaging tools, ultrasonography, computed tomography and magnetic resonance imaging, have added great diagnostic possibilities. More recent developments, such as radio nuclide imaging for the adrenal gland and the possibility of using tagged antibodies, promise to expand our imaging horizons even further. In the field of pathology, the develop ment of immunocytochemical markers (e. g. , monoclonal antibodies), the refinement in special stains and the continuous perfection of fine needle aspiration biopsies offer great new diagnostic as well as research capabil ities. Newer pharmacological agents, such as the alpha and beta blockers, the calcium channel blockers and thyroxine analogs, add a whole new level of safety to the management of the potentially lethal pheochromocytoma.

Table 1 (Continuation) Reference Subject J. DAVIS, 1957, 1960b, 1961b, 1962b, 1963a; Regulation of secretion FARRELL, 1958; BARTTER et aI. , 1959; DENTON et aI. , 1959, 1960; COGHLAN et aI. , 1960; FOURMAN, 1962; MULRow and GANONG, 1962, 1964; WRIGHT, 1962; BLAIR-WEST et al. , 1963b; HOUDAS and FAVAREL- GARRIGUES, 1963 Relation of secretion to changes BARTTER, 1958 in intravascular volume Angiotensin (see Renin-angiotensin system) Blood volume and tonicity Regulation BLACK, 1954; E. BROWN et aI. , 1957; WELT, 1957; BARTTER, 1963; GAUER and HENRY, 1963 Receptors regulating SMITH, 1957 Oerebral cortex and cardiovascular function HOFF et aI. , 1963 Drugs affecting endocrine function GAUNT et al. , 1961 Erythropoietin JACOBSON, 1963; JACOBSON and DOYLE, 1963 Growth hormone (including action on adrenal cortex) FrnKEL, 1962 Hypertension Clinical and physiological aspects PAGE, 1962 SKELTON, 1959 During adrenal regeneration Renal (see Renin-angiotensin system) Russian work on SIMONSON and BROZEK, 1959 Juxtaglomerular cells Anatomy and physiology TOBIAN, 1960a, b, 1962, 1964; HATT et aI. , 1962; P. HARTROFT, 1963 Pineal and related organs KELLY, 1962 Comparative anatomy Renin-angiotensin system Chemistry, physiology, and structure- BRAUN-MENENDEZ et aI. , 1946; activity relationships BRAUN-MENENDEZ, 1956; BUMl'uS et aI. , 1961; SKEGGS, 1960; SKEGGS et aI. , 1957, 1964; PEART, 1959; GROSS and TURRIAN, 1960; PAGE and BUMl'us, 1961, 1962 Relation to hypertension in man WAKERLIN, 1955; GROSS, 1958, 1960, 1964; and animals Proceedings, Conference on Hypertension, 1958; KORNEL, 1959; TAQUINI and TAQUINI, 1961; GROSS et aI.

This volume is devoted to the chemistry, immunology, molecular biology, and physiology of the human chorionic gonadotropin, heG. For this glycoprotein molecule the course from discovery to chemical deciphering covered about fifty years. It was in 1928 that Ascheim and Zondek reported that urine from pregnant women contains something that stimulates the ovaries of mice or rats. This provided the basis for the famous A-Z test for pregnancy and for the "rabbit test" modification introduced by Friedman. As researchers sought to find more sensitive responses to heG, they used a wide variety of species including the South African aquatic toad, Xenopus Zaevis, the terrestrial toad of South America, Bufo arinarus, and the African weaver finch, EupZeetes afra. The weaver finch feather reaction was particularly noteworthy, for it disclosed a non-gonadal response to heG/LH. In retrospect, this may have been an important evolutionary clue to the realization that the designation of the hormone as a "gonadotropin" may have been only partially descriptive of the molecule's physiological function--a concept that is gaining attention, as the papers in this 1980 volume divulge.

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."

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is 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 developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It wa& decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

THE DISCOVERY OF INSULIN, C-PEPTIDE AND PROINSULlN, SPECIES DIFFERENCES Crude insulin was extracted and isolated from dog pancreases removed 7-1 Degrees weeks after ligation of the pancreatic duct for the first time in 1921 by Banting and Best. Its lifesaving properties were subsequently documented in pancreatectomized dogs in 1922. Only about six months elapsed from its discovery until systematic collection of calf and ox pancreases and, later, porcine pancreases was established and the blood glucose lowering effect in diabetics using the crude extract from these glands proven. It was not until 1960, however, that the primary structure of all three species of insulin, lO7 human, porcine and bovine, was elucidated . It then became evident that the differences between bovine, porcine and human insulin amounted to at mosl 3 amino acids. These apparently small differences have a significant impact on the physico-chemical characteristics of the three insulins which again affect, e.g., the rate of absorption of insulin lO9 preparations from the subcutaneous tissue and their immunogenicity, i.e.

Despite a new title, Contemporary Metabolism, Volume 1 is actually the third volume in a continuing series and succeeds The Year in Metabolism 1975- 1976 and The Year in Metabolism 1977. As in the earlier volumes, the same internationally recognized authorities review the noteworthy recent devel opments in their areas of expertise. In many instances they also address aspects that have not been considered previously. In this volume, Dr. J. Edwin Seegmiller again updates progress in understanding disorders of purine and pyrimidine metabolism. However, particular emphasis is placed on the emerging relationships with immune mechanisms. Dr. Charles S. Lieber is joined by Dr. Enrique Baraona in a continuing review of metabolic actions of ethanol. This chapter examines effects of ethanol on protein metabolism and selected features of lipid metabolism-two areas that were not included in the earlier volumes. Dr. DeWitt S. Goodman's review of disorders oflipid and lipoprotein metabo lism builds on his previous chapters, but much additional attention is directed to a critical analysis of recent advances in epidemiology and lipoprotein structures. In collaboration with Dr. Brian L. G. Morgan, Dr. Myron Winick devotes his entire chapter to a detailed review of the impact of nutrition upon brain development-an overview that has now been rendered possible by the burgeoning recent developments in this area."

The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap plied in neuronal tissue to the neurohypophysis.

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.

It is curious that research in endocrinology has largely ignored the testis until quite recently. There were two impor tant reasons for this neglect; first, methods of study were difficult, and second, sperinatogenesis was considered to be the concern of the urologist or cell biologist but not the endocrinologist. Since it is now almost an ethical imperative that we develop a male contraceptive, and since a host of new techniques can be brought to bear on problems of testis function, research in male reproductive biology has effloresced. In fact, it has become possible to project aseries of workshops on the testis, each dealing with discrete aspects of biochemistry, physiology and pathology. It is fitting that this first Workshop should be on Binding and Activation, since this area is one of the frontiers in endocrinol ogy. At our present rate of progress it is probable that each of the succeeding workshops will likewise bring together leaders in a rapidly developing area. The National Institute of Child Health and Human Development has the major Federal respon sibility in reproductive biology, and has therefore agreed to sponsor this and succeeding workshops. On behalf of the Institute and for those members of the Committee who have organized this meeting, I welcome you. I am quite sure that this first Workshop on the Testis will initiate aseries of important contributions to scientific thought in male reproduc tive biology. Mortimer B. Lipsett, M. D."

During the past several decades, much research effort has gone into the elucidation of the role of neuroendocrine systems as secretory and metabolic regulators of cells of a variety of organs and structures, including the testes, ovaries, adrenals, thyroid, pituitary gland, and mammary glands. However, the role of cells comprising such organs and structures in the modulation of neuroendocrine processes has received considerably less is generally less well appreciated. attention and Nonetheless, it is important that we understand the actions on neuroendocrine systems of substances that reach the brain by way of the vasculature, including hormones, cytokines, toxins, amino acids, drugs, and similar agents. In order to analyze the present state of knowledge on this topic, experimental scientists and clinicians, whose shared interests include actions of circulating agents on the brain, met at a satellite symposium of the XXXI International Congress of Physiological Sciences. This symposium, entitled Circulating Regulatory Factors and Neuroendocrine Function, was held in Smolenice Castle, Czechoslovakia, June 26-July 1, 1989, and reviews delivered at this symposium as invited presentations are published in this volume. Presentations given as free communications have been published separately and are available in Endocrinologia Experimentalis 24: 1-273, 1990.

The use of performance-enhancing substances by athletes is not a contemporary epi demic. In fact, athletes purportedly resorted to such measures over 2000 years ago. Even at the ancient olympic games, athletes employed special diets and concoctions to enhance their performance. In ancient Rome and ancient Egypt, gladiators and athletes ingested various potions in order to improve their physical endurance. In most in stances, such early examples of substance abuse by athletes involved relatively in nocuous chemicals, and one might presume that any enhanced performance could be attributed largely to a placebo effect. Nowadays, aside from the ethical issues, these performance-enhancing substances are far more potent and hence toxic to the body. The many performance-enhancing chemicals, drugs, and hormones exert a variety of complex pharmacological actions, but all are meant in some fashion to improve phys ical ability. Their pharmacological effects ranges from imprOVed muscle strength, as in the case of anabolic steroids and growth hormone, to central nervous system stimula tion, as in the case of caffeine or amphetamine. Analgesics or other pain-killing drugs may also be used to suppress an existing injury in order that the athlete may compete."

Paget's disease is an old disease historically, but a new disease therapeutic ally. Human remains unearthed in Lancashire, England, dating from ap proximately 900 AD, show clear evidence of the aftliction. However, it was not until the 1800s that physicians rediscovered the condition, and a little more than 100 years ago that Sir James Paget published a perceptive and accurate description of the disease from the clinical and pathologic points of view. He felt the disease represented an inflammatory condition of the skeleton and hence named it osteitis deformans. The condition again lapsed into anonymity for several decades afterwards, and therapeutic approaches did not evolve until after World War II when several groups, located mainly in the Boston area, began using a variety of agents, includ ing corticosteroids for treatment of this condition. These early attempts at therapy were unsuccessful and the condition remained essentially untreat able until the development of the calcitonins and the bisphosphonates in the 1970s. In 1978, the Paget's Disease Foundation, a private nonprofit volun tary health agency, was founded to assist individuals aftlicted by Paget's disease of bone, to provide education regarding this condition to the medical community, and to encourage research efforts to better under stand and treat the condition. An international conference was organized under the aegis of the Paget's Disease Foundation and was held in New York City in October, 1989, ten years after the founding of the Paget's Disease Foundation."

Diagnostic Methods in Clinical Thyroidology provides a forum for discussion of controversial issues in three major categories: diagnosis of thyroid function, non-invasive evaluation of structural abnormalities, and needle biopsy diagnosis of thyroid nodules. For each category, a free interchange of ideas based on extensive clinical experience is followed by a summary that strives to resolve these controversial issues within a framework of sound clinical practice. The volume will this serve as a ready reference for the many physicians who evaluate thyroid patients.

The cytochemical bioassay system was described in a short abstract in 1971, and more fully, in the cytochemical bioassay of corticotrophin, in 1972. Since then, cytochemical bioassays have been described for several polypeptide hormones, and these assays are already widely used. It is expedient that the subject should be reviewed, as it is in this monograph, by one writer who has had the good fortune to have taken part in the growth of cytochemistry from its early origins to its present position as the basis of possibly the most sensitive bioassay system currently available. However, it should be noted that major contributions have been made by many, both to the development of the subject and to the establishment of the bioassays. The object of this preface is to try to give some perspective to the growth of this subject and to record that the cytochemical bioassay system has been fostered by many outstanding scientists in an atmosphere of remarkable goodwill. To begin with, there could have been no cytochemical bioassays until cytochem istry had been converted from its rather unsure origins into a precise and quantitative form of cellular biochemistry. This was done with skill and enthusiastic dedication by my colleagues, Dr. Lucille Bitensky, Dr. F. P. Altman, Dr. R. G. L. W. Poulter and Mr. A. A. Silcox, first at the Royal College of Butcher, Dr."

For many years, patients who complained of prostatism had only a few treatment choices. The patient was either a candidate for an elective prostatectomy, or the operation was deferred until the patient became more symptomatic. The present text summarizes the multiple options which have become available to the practicing urologist. Minimally invasive techniques such as transurethral incision of the prostate, balloon dilatation, hyperthermia, laser therapy, and prostatic stents are described. Medical treatment with alpha-blockers, 5 alpha-reductase inhibitors, and flutamide are addressed by authors who have had extensive clinical experience with the use of these agents.

Acromegaly is a relatively rare chronic disease. Nevertheless, it is life-threatening in its sequelae, for example, hypertension and cardiovascular disease. Since it also has disfiguring properties - especially of the head and face - acromegaly has serious psychological consequences which are reinforced by the awareness of factors such as excessive sweating. It is precisely on these signs and symptoms that Sandostatin R has a rapid effect, thus improving the patient's quality of life as well as counteracting the underlying processes. SandostatinE

All the important pharmacological interactions affecting thyroid function are described in this book. The first section is devoted to the physiology and biochemistry of thyroid disease, putting the pharmacological interactions into perspective. The second section reviews all the important pharmacological effects on thyroid function and also deals with the impact of other environmental agents. The chapters are written by internationally recognised experts and extensively referenced to provide an up-to-date review of the pharmacological interactions important to the thyroid and its diseases.

The actions of honnones upon systems outside of the usual target sites for such molecules represents an area of increasing interest and growing clinical significance. This volume represents a cross-section of such actions of honnones upon several relevant sites. In the first chapter of this volume Dr. Malick discusses the current status of endorphins as analgesic agents. It is now known that a more primary level of control exists for iJ-endorphin in that a 41-amino acid pep- tide has been isolated from ovine hypothalamus; this peptide stimulates iJ-endorphin release as well as the secretion of corticotropin (Vale et al. , 1981). The analgesic properties of corticotropin and its immunoactive-like analogs are well known. so it does not come as a surprise that these two classes of analgesic peptides are regulated by a common hypothalamic con- trol peptide. It may also be of interest to observe that an increase in iJ-en- dorphin concentration in the pituitary occurs in genetically obese mice and rats, and that such obesity can be attenuated through the administration of nalaxone (Margules et al. , 1978). It has also been determined that genet- ically obese mice have a probable cholecystokinin deficiency in the cerebral cortex in that this peptide is a satiety-inducing agent (Saito, et al. , 1981). The analgesic properties of the latter have also been observed. The extra-pituitary actions of another pituitary peptide, as examined in the second chapter of this volume by Dr.

Traditions are dangerous; doubly so in science. Traditions are unchanging; science is about change. This was the 4th International Colloquium on Carbohydrate Metabolism in Pregnancy and the Newborn to be held in Aberdeen, and by now the form is set. How much its content has changed is a matter of nice judgement and not under the control of the organizers. It is not within their power to bring news of revolution, if there has been no revolution. Certainly many of the speakers had kent faces from previous Aberdeen meetings, but so they would be at any meeting on diabetes anywhere in the world. The written proceedings of scientific conferences have purposes other than to record changes: sometimes they need to state a consensus. The 3rd Colloquium came to an agreement about the importance of prepregnancy recognition and control of abnormalities of carbohydrate metabolism. The 4th set out to examine what results it had achieved. Much of this book is taken up with follow-up studies of the applications of similar regimes in different parts of the world. Since the first Aberdeen meeting in 1973, progress in the manage ment of diabetic pregnancy has been slow and steady, but the change in the city and the society where the meetings took place has been fast.

Endocrine Neoplasia is a comprehensive, updated, and clearly-written text covering the diseases for which endocrine surgical expertise is often needed. We look towards advances in the science and the art of endocrine surgery to continuously improve outcomes for our patients. The goal of this text was to provide a detailed description of both the underlying science of disease as well as the art of clinical management.

The book is divided into five sections addressing neoplasms of the thyroid, parathyroid, adrenal gland, neuroendocrine pancreas, and multiple endocrine neoplasia. Experts from the United States, Canada, and Australia have contributed chapters addressing both the biology of endocrine tumors and the clinical management of disease. Recent discoveries regarding the genetic underpinnings of disease are highlighted. Updated consensus guidelines were used for clinical recommendations. The management of complex and often confusing clinical problems is discussed in detail.

The unraveling of our knowledge of the functions of the adrenal gland constitutes one exciting development of modern medicine and biochemistry. We owe these advances to the felicitous cooperative efforts of the clinical investigator and the biochemist. Three centuries elapsed between the first recorded anatomical descrip tion of the adrenals and the demonstration by Dr. Addison in the mid-nineteenth century of the fatal results of the destruction of these glands by disease. It became evident from this observation that the adrenals secreted a "factor" or "factors" essential to life. It took approximately 90 years to isolate this elusive vital factor - cortisone - from beef adrenal cortices, independently by both Reichstein and his co-workers in Basle and Kendall and his group in the United States and another 10-15 years before it became more generally available for experimental and clinical use. It is perhaps difficult to believe that as recently as 35-40 years ago, before cortisone and cortisol were clinically available, the surgical removal of a benign adrenal cortical tumor in patients with Cushing's syndrome was associated with a prohibitive postoperative mortality rate. Within 12-36 h after operation, most of such patients developed an intractable state of shock, which was not manifested by significant electrolyte abnormalities or hypoglycemia and was unresponsive to the usual treatment for shock plus the generous use of salt-retaining hormone.