The Department of Continuing Education of Harvard Medical School and members of the faculty of Harvard Medical School held a multidisciplinary course on the management of patients with urologic cancer in the fall of 1982. This course high lighted the multidisciplinary approach to the care of these patients, and outlined the clinical and pathophysiological basis for diagnosis and treatment. The term multidisciplinary was essential to the course in which the disciplines of uro logic surgery, medical oncology, and radiation therapy were each appropriately emphasized. Widespread interest in the contents of this course, and the timely and useful nature of much of the information presented there, has encouraged us to publish, in as rapid a manner as possible, new information and highlights of that course. A camera-ready format was used to allow rapid production, and a variety of disparate styles were maintained from chapter to chapter--some in prose, others in outline. Again, our intent was to disseminate information rapidly and accurately, and to that end, we felt that consistency of style was irrelevant."

Heart and brain interaction is an increasingly vital area of clinical investigation. This is the most comprehensive review of the subject available, presented by internationally recognized authorities in the field. The book offers extensive coverage of cardioembolic stroke, including a brand new contribution on the mechanism of hemorrhagic infarction. Controversial topics such as anticoagulation, combined carotid and coronary surgery and screening for silent coronary disease are covered. Also included are a comprehensive review of the cardiovascular/neurobiological role of the central nervous system in hypertension and sudden death, and a practical approach to the patient with syncope. This integrated, topical presentation makes essential reading for neurologists, cardiologists, internists and anyone caring for patients with stroke or cardiac disease.

Advanced Renal Cell Carcinoma (RCC) cannot be cured by surgery alone. Its resillience to irradiation and chemotherapy demands a new approach to the management of this disease. This book provides an overview of the scientific and clinical developments of RCC, and clarifies the fields ofimmunotherapy and immunobiology. The book contains a compilation of approaches that will enhance the effectiveness of the management of advancedRCC, even in the absence of definitive pre-clinical data. These require additional study and will stimulate the reassessment of preliminary results.Furthermore, preliminary results of already implemented clinical trials withbiological modifiers are presented. Of special interest are the current achievements in the field of immunotherapy using topically and subcutaneously low dosage combinations of cytokines. This concise volume will benefit those seeking a thorough review of the research and the clinical aspects of RCC simultaneously.

Congenital adrenal hyperplasia (CAH) consists of a group of disorders of adrenal steroidogenesis. Each disorder results from an inherited deficiency of one of the several enzymes necessary for normal steroid synthesis. The different enzyme deficiencies produce characteristic patterns of hormonal abnormalities; the clinical symptoms of the different forms of CAH depend on the particular hormones that are deficient or that are produced in excess. The earliest documented description of CAH was by DeCrecchio in 1865 (DeCrecchio 1865). This Neapolitan anatomist described a cadaver having a penis with first degree hypospadias but no externally palpable gonads. Dis- section revealed a vagina, uterus, fallopian tubes, ovaries, and markedly enlarged adrenals. It is interesting that the subject suffered a confusion of sex assignment, being declared a female at birth and a male 4 years later. He conducted himself as a male sexually and socially. Since the original descrip- tion of this case, investigators have unravelled the pathophysiology of the inborn errors of steroidogenesis. 1 Steroidogenesis and Enzymatic Conversions of Adrenal Steroid Hormones A. Steroidogenesis The adrenal synthesizes three main classes of hormones: mineralocorticoids (17-deoxy pathway), glucocorticoids (17-hydroxy pathway), and sex steroids.

For the last two decades, the topic of chronic renal failure has been dominated by discussions on dialysis and transplantation. As facilities for treating patients with end-stage renal failure have become more readily available, at least in Europe and North America, attention has once again been drawn to conservative measures which may improve both the overall prognosis and the quality of life of patients with renal impairment. Although severe renal failure may be progressive and many patients will ultimately require some form of renal replacement therapy, it is now widely appreciated that distressing symptoms can often be ameliorated by judicious medical treatment. Children as well as, and perhaps to a greater extent than, adults may benefit from such therapy. This volume examines relevant trends in the conservative man agement of both adults and children with chronic renal failure. Each chapter has been written by recognized experts and provides infor mation of clinical relevance for the average clinician. As the overall prognosis for patients with end-stage renal failure improves it is clear the management of patients with relatively stable chronic renal failure is an important topic not only for nephrologists but for all practising clinicians."

The human prostate gland is of undoubted importance in reproductive physiology and is one of the commonest causes of clinical urological problems in the male patient. Despite the wealth of published lit erature relating to the prostate gland surprisingly little is understood about its neural innervation, the influence of pharmacological factors and its precise physiological functions. Indeed, benign disorders of the prostate gland including benign prostatic hyperplasia, bladder neck dyssynergia and inflammatory disorders of the prostate (prostatitis, prostatodynia) although well recognised clinically, are as yet poorly characterised and understood. It was not until the late 1960s that the subject of urodynamics, which for the first time allowed scientific assessment of the function of the lower urinary tract, was introduced. The first section of this book considers recent advances in our understanding of the innervation of the bladder and prostate gland and the changes in bladder function which accompany prostate medi ated bladder outflow obstruction. The clinical consequence of benign prostatic hyperplasia in many patients is bladder outflow obstruction and although the traditional treatment of these conditions is by the use of ablative surgery, in recent years a number of new modalities have been investigated and are reviewed in the second section of the book.

The action of diuretics including cellular mechanisms of action, pharmacokinetics, and clinical usage, with much emphasis placed on the most recent findings on the pharmacodynamics of the respective drugs. During the past twenty-five years since volume 14 on Diuretica was published in the Handbook series, the cellular mechanisms of action of diuretics have slowly been unravelled. Today, the role of action within the target cells is known for most of the substances discussed. This has provided a new basis not only for the understanding of drug action but also for secondary effects and interactions. The book represents a comprehensive reference work on the diverse groups of diuretics which are among the most frequently prescribed medications.

This volume is based on a very successful meeting on organ transplantation that was held in Kuwait in 1990 under the auspices of the Middle East Society for Organ Transplantation. An international group of organ transplant experts attended this conference and their contributions and deliberations have been recent1y updated to produce this definitive and authoritative summary of current clinic al practice in organ transplantation. The initial chapters appropriately focus on the immunology of organ trans plantation with special emphasis on the initial events in the induction of alloreactivity, the mechanisms of rejection, and the potential for tolerance induction. A strong emphasis is placed on the diagnosis of rejection by cellular analysis. The section on immunosuppression deals with several new areas of clinical therapy. The section on renal transplantation is unique in several respects, the long-term results from various countries, including the Middle East, are summarized, the use of living unrelated donors and of ABO incom patible donors - all strategies to maximize organ availability - are presented."

After the positive response which followed the first edition of this book 6 years ago, the editors were encouraged to prepare a completely reworked second edition that includes the modern advances in this field. There has been a complete change of diagnostic procedure in the detection of renal tumors, which is now based on sonography, computed tomography, and nuclear magnetic resonance imaging, pushing intravenous urography and angiography completely into the background. Also, new methods of treat ment with radionuclides using embolisation are incorporated. The description of morphological structures forms the basis for under standing and recognising pathology of the kidneys and adrenals. The con tents of pathological morphology could be extended, as we are of the opinion that the detection and therapy of renal and adrenal tumors are derived from different areas of diagnostic science. We are indebted to Springer-Verlag for the excellent book production. On behalf of all the authors, we would like to thank our colleagues and associates for their cooperation in the realisation of this project. The editors hope that this volume will be of interest to radiologists, pa thologists, urologists, pediatrists, and also radiotherapists. Essen, April 1987 EBERHARD LOHR LUTZ-DIETRICH LEDER Table of Contents Pathology of Renal and Adrenal Neoplasms LEDER, L.-D., RICHTER, H.l.

The 1992 International Yearbook of Nephrology is the 4th in a successful series of yearly books updating practising nephrologists and nephrologists-in-training on rapidly changing areas of nephrology. We were encouraged to proceed in our editorial venture by reviews of the previous issues which have appeared in various Nephrology Journals. These reviews have pointed to the successful use of the International Editorial Board, the broad range of topics of current interest which have been covered and the comprehensive and practical nature of the reviews. The principal aim of the Yearbook remains to provide reviews which are more current than those which appear in Nephrology textbooks and which can be in the hands of the readers a few months after the authors have completed the manuscripts. The appointed authors are always experts in the field, who are asked to give an objective review of the topic, up-dating the readers on the world-wide literature and providing them with a complete, accurate and up-ta-date list of important recent references. We have decided to maintain the successful format of the first three issues. Thus, the volume will continue to be divided into sections; each section will continue to have a different primary focus every year, depending upon what is of greatest interest at the time.

Glutamine is a key aminoacid for the synthesis of numerous biologic- ally important compounds in mammalian cells and is a carrier form of ammonia. The advance in knowledge on the metabolic significance of this amino acid is presented in in-depth treatments by experts in this active research field. This includes the enzymology of glutamine synthe- tase and glutaminase activities in different mammalian organs, notably liver, kidney and brain; properties of glutamine transport across bio- logical membranes; role of glutamine metabolism in the liver, with emphasis on the recent discovery of intercellular heterogeneity with respect to enzyme distribution and its functional consequences for ammonia/urea metabolism and pH regulation; renal and intestinal glutamine metabolism; cerebral glutamine/ glutamate interrelationships; skeletal muscle; role of glutamine in cell culture; and finally the clinical aspects, including the new outlook of glutamine antagonists in cancer therapy as well as the role of glutamine in hepatic coma and encephalo- pathy. Some, but not all, of the contributors to this work attended the 48th Conference of the Gesellschaft fur Biologische Chemie on glutamine metabolism held in Gottingen, W. Germany, in September 1983. This conference was supported by the Stiftung Volkswagenwerk, Dr. H. Falk Foundation, Freiburg, and the J. Pfrimmer Co. , Erlangen. The abstracts of the contributions to the conference were published in Hoppe-Seyler's Z. Physiol. Chem. 364,1237-125,6,1983, and this book is not intended as the proceedings of that meeting.

This book started out as a "Manual. " The idea was to offer straightforward instruction on how to handle patients in whom renal function is altered by intrinsic as well as systemic or extrarenal disease. While we have attempted to provide simple approaches to most conditions, we have gone beyond that and offer here more detailed description of pathophysiology, diagnosis and therapy. Thus, the "Manual" has become a Handbook. In so doing we hope we have widened the audience for which the book may be useful. As it now stands, we envision that students, house staff, nephrology trainees, nephrologists, primary-care physicians, and nurses of specialized units, interested in kidney-related disturbances and in alterations of the composi tion of the extracellular fluid, will benefit from reading the Handbook. While providing a rational background for the treatments outlined, each author has attempted to narrate the reasons why such therapy is utilized. Frequently, the information is provided in tables and figures to which ready reference can be made. The flow-chart approach has also been utilized to illustrate pathophysiological sequence or steps in therapy. In most instances, the discussion of pathophysiology has been limited to what is widely ac cepted rather than treading into anything controversial, unless the nature of the problem or the nature of our knowledge is ambiguous."

Nephrology, initially born as a small branch of medicine, has, in the last few decades, become an extraordinary large field of medicine. The recent development of renal medicine is mirrored by the numerous nephrological journals published, a natural consequence of the increasing number of basic and clinical research studies performed continuously all over the world. Undoubtedly the progress which has occurred in the different, specific fields of renal medicine has given rise to subspecialities which range from renal physiology and pathology to hemo- and peritoneal dialysis and renal transplantation. Even the diagnostic methodology in nephrology, very useful in the clinical practice, has become a speciality within the speciality. Thus, the problem for clinical nephrologists, as well as for internists, is to remain continuously up-dated in all fields of nephrology. Nephrology textbooks are published continuously and in great number. However, the time required for having authors appointed, chapters completed, manuscript edited, galley proofs corrected and the whole book printed makes many textbooks already out of date when they go on sale and their half lives are very short. On the other hand, nephrological journals are so many and the articles so numerous and detailed, that it is often impossible to rely on them for up-dating practicing clinicians.

The hemodynamic mechanisms of hypertension are often limited to the study of three dominant parameters: blood pressure, cardiac output and vascular resis tance. Accordingly, the development of hypertension is usually analyzed in terms of a 'struggle' between cardiac output and vascular resistance, resulting in the classical pattern of normal cardiac output and increased vascular resistance, thus indicating a reduction in the caliber of small arteries. However, during the past years, the clinical management of hypertension has largely modified these simple views. While an adequate control of blood pressure may be obtained with antihypertensive drugs, arterial complications may occur, involving mainly the coronary circulation and suggesting that several parts of the cardiovascular system are altered in hypertension. Indeed, disturbances in the arterial and the venous system had already been noticed in animal hypertension. The basic assumption in this book is that the overall cardiovascular system is involved in the mechanisms of the elevated blood pressure in patients with hypertension: not only the heart and small arteries, but also the large arteries and the venous system. For that reason, the following points are emphasized. First, the cardiovascular system in hypertension must be studied not only in terms of steady flow but also by taking into account the pulsatile components of the heart and the arterial systems. Second, arterial and venous compliances are altered in hypertension and probably reflect intrinsic alterations of the vascular wall."

The Proceedings of the Fifth International Pediatric Nephrology Symposia are dedicated to those who make the writing possible: the delegates; those who wanted to attend, but could not, and to our colleagues, families and friends who helped organize the meeting. with the advent of certification of pediatric nephrologists in the USA and the increasing numbers of pediatric nephrologists contributing to and practic ing this specialty throughout the world, it is appropriate that we begin to record our international symposia in order to periodically document the State of the Art of pediatric nephrology and to share new information in a timely fashion with colleagues who care for children. Four previous international pediatric nephrology symposia have been spon sored by the International Pediatric Nephrology Association. These meetings were held in Guadalajara, Mexico, 1968, Paris, France, 1971, Washington, DC, USA, 1974 and Helsinki, Finalnd, 1977. This is the first time that it has been possible to organize the publication of the proceedings of a symposium. The enclosed manuscripts represent more than seventy percent of the symposia presentations delivered at the Fifth International Pediatric Symposia (October 6-10, 1980, Phila., PAl which was - hosted by St. Christopher's Hospital for Children and The Children's Hospital of Philadelphia representing the Departments of Pediatrics of Temple University School of Medicine and The University of Pennsylvania School of Medicine."

We would like to take this opportunity of expressing our sincerest thanks to the many persons who have made adrenal tissue and related materials available to us for our work. Our especial gratitude is extended to Drs. J. J. Brown, A. Lever and J. I. S. Robertson of the M.R.C. Blood Pressure Unit, Glasgow, Dr. J. K. Grant, Royal Infirmary, Glasgow, Professor R. B. Welbourn and Dr. W. Kelly, Royal Postgraduate Medical School, Drs. D. B. Grant of Great Ormond Street, J. Ginsberg, Royal Free Hospital, D. C. Anderson, Hope Hospital, Salford, C. R. Edwards, St. Bartholomew's Hospital and Professor I. Doniach (for merly of the London Hospital) and Messrs. J.-c. Gazet, A. McKinna and P. Greening, Royal Marsden Hospital, London. The preparation and presentation of the material and the results would not have been possible without the help of Dr. P. Monaghan and his Electron Microscopy Unit, Ludwig Institute for Cancer Research (London Branch), Sutton, Mrs. Mitchell and her Histology Team, Royal Marsden Hospital, Sutton, Mr. K. Moreman of the Photographic Department of the Royal Marsden Hospital and Institute of Cancer Research, London and Mr. M. Hughes for graphics. Particular thanks are due for the untiring efforts and assistance ofMr. J. Ellis and Mrs. D. Corney of the Ludwig Institute for Cancer Research (London Branch), Sutton, for most of the photographic and secretarial work respectively. Professors G. Dhom and E. Mausle kindly provided material for Figs."

Vittorio E. Andreucci of keeping alive patients in terminal chronic Initially created with the purpose renal failure, dialysis has undergone improvements in methodology, and its final goal has become complete health rehabilitation and optimization of the quality of life of chronic dialysis patients. To achieve this, many investigators have attempted to increase dialysis efficiency and at the same time shorten dialysis time. Their main concern was, obviously, patient safety: the Latin proverb 'primum non nocere' is still valid all over the world. Thus, when clinical observations of the first patients on regular dialysis therapy suggested an inverse relationship between duration of dialysis sessions and severity of peripheral neuropathy, long and frequent dialysis sessions were considered the only way to prevent the catastrophic consequences of nerve damage and underdialysis syndrome. It was then, in 1971, when dialysis duration was 8- 12 hours per session, that Vincenzo Cambi started a 'short dialysis' trial, i. e. , 4 hours 3 times weekly or 3 hours every second day. For the first time, dialysis was shortened from 24-36 hours weekly to 10. 5-12 hours weekly [1, 2]. In 1971 I was still at the Parma University Hospital. We had both just returned from the United States, and Dr. Cambi was responsible for the dia lysis unit.

Increasing the accumulation of aluminum in the bone (body) in cases of renal osteodystrophy may influence the histopathologic aspect of the bones. Alumi- num blunts the effect of increased PTH secretion and favours the genesis of osteoid. That means, in cases of renal failure combined with aluminum accumulation, a relatively low bone tunover is found and no fibrosis of the bone marrow. Furthermore the amount of osteoid is increased. This means that there is evidence of osteomalacia especially when the latter is defined as an increased amount of osteoid covered with a relatively low number of cubic osteoblasts. To a certain extent the effect of aluminum accumulation is comparable to the effect of PTX. Treatment with DFO may normalize the bone, although not necessarily with a concomittant disappearance of alumi- num from the bone. The presence of aluminum in the bone can be suggested by routine histologic investigation of the bone and can be made rather probably by the aluminum staining combined with iron-staining, but can only be proven by more advanced techniques like ET AAS and LAMMA. References 1. Boyce BF, Elder HY, Elliot HL, Fogelman I, Gell GS, lunor Bl, Beastall G, Boyle YT, 1982: Hypercaicaemic ostemalacia due to aluminium toxicity. Lancet 6: 1009. 2. Verbueken AH, Visser Wl, Van de Vyver FL, Van Grieken RE, De Broe ME, 1986: The use of laser microprobe mass analysis (LAMMA) to control the staining of aluminum by aurin tricarboxylate (aluminon). Stain Technology 61: 287.

MRI has opened up new possibilities in combined morphological and functional imaging, and now there is a book which discusses both aspects together. Two systems which already demonstrate the advantages of MRI are presented. In the cardiovascular system, motion and flow can be imaged so that even flow velocities in the deep vessels of the body can be measured, and turbulences can be identified. In the study of the kidneys, a combination of renally excreted contrast media and imaging provides within seconds insight into glomerular filtration in health and disease. These current possibilities, and their limitations, bring insight into the future potential of MRI.

The purpose of this book is to provide the reader with a rational frame of reference for assessing the pathophysiology of those disorders in which derangements of membrane transport processes are a major factor responsible for the clinical manifestations of disease. In the present context, we use the term "membrane transport processes" in a catholic sense, to refer to those molecular processes whose cardinal function, broadly speaking, is the vectorial transfer of molecules- either individually or as ensembles-across biological interfaces, the latter includ- ing those interfaces which separate different intracellular compartments, the cellu- lar and extracellular compartments, and secreted fluids-such as glomerular fil- trate-and extracellular fluids. Evidently, consideration of these processes, and of the pathophysiology of membrane disorders, requires an understanding of the composition and structure of biomembranes, of the physical rules governing mem- brane transport processes, of the way in which chemical regulators-either physio- logic or pharmacologic-regulate or modify membrane transport processes, and of the ways in which these events are interpreted into specialized phenomena such as cell volume regulation, signal transmission in excitable tissues, cell-to-cell commu- nication, and secretory processes in epithelia. Accordingly, Physiology of Membrane Disorders is divided into five major sections. Part 1, The Nature of Biological Membranes, provides an overview ofthe physical structure and composition of plasma membranes, and of the dynamic relations between structure and function.

Malignancies are frequent complications in organ transplantation, mainly as the result of infection with certain viruses and of long-term immunosuppression. The epidemiology confirms that the increased incidence concerns certain cancers, especially HIV-related skin cancers and EBV-related lymphoproliferative malignancies. This book covers all currently available information on this important topic of the relationships between transplantation and malignancies: preexisting cancers, posttransplant cancers, their etiology and pathophysiology, their prevention and treatment. A significant part of the volume is devoted to prophylaxis, early detection and modern forms of therapy in posttransplant lymphomas. As a conclusion of all these new data, the theory of immunosurveillance deserves to be significantly modified.

The thrust here is for those who want to know more than the answer to an exam question - an approach to disease diagnosis and treatment which emphasizes thoughtful consideration of alternatives, finding ones way through uncertainties and lack of knowledge. The annual seminar on which this volume is based has evolved into a forum for open discussion of puzzling questions - actually old questions in the light of new data. To me, the adventure of life is in recognizing the openendedness of all things. So you thought that a certain disease was a settled question? In medicine a "settled" question is a transient conclusion. Even the solutions to the so-called simplest problems have another side. Our aim this year was to air out concepts and conclusions about hypertension, fluid-electrolytes, and tubulopathies. The stars were Drs. Juan Rodriguez-Soriano, Alan Gruskin, and Donald Potter, along with Drs. Gustavo Gordillo, Ronald Kallen, and Antonia Novello as guest faculty. Local stars included Drs. Mary Jane Jesse, Jacques Bourgoignie, and Carlos Vaamonde. Their contributions added to those of the other faculty and registrants, coalesced into vibrant exchanges which are reproduced here for the reader's perusal.

My thoughts about the Hemolytic Uremic Syndrome (HUS) got started in 1961 along with my attempt to return to Argentina. As I sought my way in Buenos Aires, I visited Carlos Gianantonio whom I had met in Caracas the year before during the Pan American pediatric meetings. At that time he was actively working on HUS which had become an epidemic in Buenos Aires and other parts of Argentina. I was impressed by the team effort and devotion of his group to such heavy demands. They obviously were meeting the challenge at an amazingly high level under a very crippling physical situation with shortages of space, laboratories and equipment. His group together with Dr. Becu, at the time the pathologist at the Children's Hospital of Buenos Aires (we had met through his mother who was instrumental in arranging my return to Buenos Aires), wrote some of the classic papers on HUS. Through the years as Dr. Gianantonio became more involved in general pediatrics, the administrative aspects and its orientation in Latin America, he became known for his deep philosophical questions as to what we are doing and where we are going. His questions have obvious implications regarding an agressive approach to our pediatric nephrology patients.

Enormous progress has been made in the treatment of chronic renal failure over the last decades. Until the 1950s, chronic renal failure was considered to be an inexorably lethal condition. This is no longer the case. In addition, the disease, severe uremic syndrome, is now extremely rare, if existent at all, in industrialized countries. Physicians of my generation who saw patients hospitalized with hemor raghes, pericarditis, severe anemia, cardiac failure, "malignant hypertension," pruritus, vomiting, generalized edema, and convulsions are particularly grate ful for this progress. I well remember seeing such patients hospitalized in the last days or weeks of their lives and also remember the sense of impotence I suffered for the com plete lack of efficient measures I had at my disposal to manage their condition. Nowadays, hemodialysis, peritoneal dialysis, and kidney transplantation allow patients with chronic renal failure to survive for very long periods of time in a satisfactory condition. Why then is there still a sense of dissatisfaction and why should we study dietary management? The drawbacks of dialysis and transplantation are the main reasons, but the certainty that dietary therapy is complementary to dialysis and even better than dialysis in certain conditions, is also very important."