A workshop was organised in order to achieve multi-discipli- nary review of the pathogenesis and management of acute failure, particularly as it occurs and is managed in intensive therapy units. The book deals with the realities and practicalities of this important area of acute medicine. Each chapter is followed by a discussion, so that a concen- sus view is obtained from an international body of experts.

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.

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.

For more than a century, the condition now known as Idiopathic Hydronephrosis has been recognised as a clinical entity, and following the original description by Rayer in 1841 a variety of procedures were devised in attempts to correct the condition surgically. Most of these early methods were introduced in the last decade of the nineteenth century by several illustrious clinicians, including Trendelenburg, KOster, Fenger and Sutton. For many years diagnosis was based purely upon the patients presenting signs and symptoms and not until the early part of this century was technology available to assist in the pre-operative diagnosis of the condition. Early methods depended upon radiological techniques, and the introduction of the retrograde pyelogram by Voelcker and Lichtenberg in 1906 represented a significant advance in diagnostic methodology. Other methods also dependent upon radiographic techniques were subsequently introduced, including urography in the late 1930s by Swick, and more recently, the method of cineradio graphy, as pioneered with considerable success by Peter Narath in the decade following World War II. During the past 50 years a variety of surgical procedures have been introduced for the treatment of idiopathic hydronephrosis. That so many different methods have been devised suggests that no one specific technique is capable of achieving a complete cure in all cases."

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."

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.

One of the time-honored foundations of the practice of pediatric medicine is the understanding and application of the principles of fluid, electrolyte and acid-base disorders. Presented in a new softcover format, "Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook" brings together a select group of authors who share a passion and an appreciation of the contributions of pioneers in pediatric medicine and an expertise for their respective areas in a new softcover edition. The volume provides in-depth discussions of the basic functioning of the kidneys, skin and the lungs. Each chapter describes the etiology and demographics, biological mechanisms, patient presentation characteristics, therapy options and consequences of optimal treatment as well as delayed treatment. "Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook" provides health professionals in many areas of research and practice with the most up-to-date, accessible, and well referenced volume on the importance of the maintenance of fluid and electrolyte concentrations in the pediatric population, especially under acute care.

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.

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.

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.

I am honored to be invited to prepare a foreword for the proceedings of the Second International Lubeck Conference on Erythropoietin (Epo). I congratulate Wolfgang Jelkmann, Horst Pagel and Christoph Weiss for their organization of an excellent program for this conference which updated all of us on the advances made in erythropoietin research during the past few years since the first conference in June of 1988. I am sure that Professor Paul Carnot, had he been present at this conference, would be very pleased and proud of the advances made in the field of erythropoietin since his and Madame DeFlandre's seminal finding in 1906 (1) that rabbits produced a humoral substance following bleeding which controls red blood cell production. The reports by Hjort in 1936 (2) and by Erslev in 1953 (3) that large volumes of plasma or serum from rabbits following a bleeding stimulus, when injected into normal donor rabbits, produced a reticulocytosis, were very significant in confirming the existence of a humoral factor which controls erythropoiesis. Reissmann's parabiotic rat experiments in 1950 (4) reawakened interest in erythropoietin when he proved that hypoxia stimulated the production of a factor which regulates red cell produc tion. The studies of several investigators such as Jacobson et al. (5), Fisher and Birdwell (6), Kuratowska et al. (7) and Nathan et al."

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."

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.

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.

Anil K. Mandai, M.D., is one of the trailblazers in the use of the transmission electron microscope in the study of the urinary sediment. In this book, he reviews his extensive efforts to tie his vast clinical expe rience to his elegant basic research with the electron microscope. The pictures are comprehensive, and the clinical correlates are nicely outlined in tables and text. It may astonish some readers that a book for fellows and clinical nephrol ogists has been written on the use of the transmission electron microscope in the study of urine. Some may view this as a sophisticated research instrument. I, however, applaud the effort. So many discoveries and advances in basic science lie unutilized because clinicians are not aware of the tools available or have little instruction in their use. Maybe that is the reason why so many tests have come and gone, have been found useless and dropped, or have simply been abandoned after being judged too complicated-some because they were, others because they were never applied and interpreted properly. The whole field of research seems to be pulling ahead and away from clinical medicine. Therefore, an effort like this one, which rapidly and clearly tries to introduce an advanced research examination technique into clinical medicine, is worthy of admiration and sup port."

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.

Genetic disorders have emerged as a prominent cause of morbidity and mor tality among infants and adults. As many as 10% to 20% of hospital admis sions and at least 10% of the mortality in this age group are due to inherited diseases. There are at least two factors that have brought genetic disorders into the forefront of pediatrics. One is a great reduction in childhood mortality due to infections and nutritional deficiency states, and the other is the rapid progress made in the identification of genetic defects. Amniocentesis, chorionic villus sampling, and recombinant DNA technology have already had a tremendous impact on the practice of medicine. This is why the first two chapters of this volume are dedicated to general principles of molecular genetics and to a description of the techniques used to diagnose genetic disorders at the DNA level. The relevance of this new area of science to the study of inherited renal diseases is reflected in the large body of knowledge that has been generated regarding the association between various glomerular nephritides and genetic markers such as the HLA system, and even more impressively in the direct or indirect identification of abnormal genes or gene products in Alport's syn drome, autosomal dominant polycystic kidney disease, and Lowe's syndrome. These discoveries figure prominently in the pages of this book. Yet, the progress we have made has barely scratched the surface of the problem."

Ever since Richard Bright discovered the link between kidney disease and cardiac hypertrophy inhispioneeringworkin 1827, thefieldofrenovascularandrenal parenchy matous hypertension has been a transatlantic adventure. Towards the end of the nine teenth century, Tigerstedt and Bergman discovered that the kidneys contain a factor whichraisedbloodpressurewheninjected intointactanimals. Theynamedthesubstance renin, which is now known as the crucial enzyme activating the angiotensin aldosterone system, which is so pertinent in the regulation of blood pressure and kidney function. After this crucial European contribution to the field, Harry Goldblatt at the Cleveland Clinic demonstrated in his classical experiments that reduction in renal blood flow, by placing a clamp at the major renal artery, could induce sustained hypertension. These discoveries established the role of the kidney in certain forms of hypertension which are now classified as renovascular and renal parenchymatous hypertension. These fundamental concepts suggested - based on experimental evidence - that restoration of blood flow or nephrectomy in unilateral parenchymatous disease would lead to blood pressure normalization in these patients. Indeed, as early as the first half of this century, a report appeared demonstrating blood pressure normalization in a child with fibromusculardisplasiaofthe right renalartery after nephrectomy. Advances in surgical techniques later allowed reconstructive renovascular surgery and therefore a more appropriate form of therapy of the disease. In the late seventies Andreas Grtinzig initiated another European contribution to renovascular hypertension by introducting the procedure of percuteaneous transluminal angioplasty, an elegant catheter technique allowing non-surgical therapy of renovascular disease."

The purpose of this book is to provide information for the nephrologist to gain a perspective on the medical, scientific, and technical aspects of reprocess ing of hemodialyzers. The book is also designed to serve the needs of the associated medical, nursing, and technical staffs of dialysis facilities for data on reuse of hemodialyzers. As an information source, the book will prove to be useful for those who may be considering reprocessing of dialyzers, as well as persons who are currently involved in this aspect of the practice of nephrology. We have focused on the clinical and technological aspects of hemodialyzer reprocessing and have not dealt with socioeconomic considerations. We do wish to share with physicians performing hemodialysis several observations we have made as a result of assembling this volume. We believe that hemodialyzer reuse has had a beneficial impact on the quality of care for hemodialysis patients in consideration of the following factors. There is an increased awareness of membrane biocompatibility issues that has been brought to the forefront with the application of reuse. Utilization ofhemodialyzer reprocess ing has enabled nephrologists . to compare the effect of various measures on biocompatibility when the patient is exposed to either a new or a reprocessed device. Previously, few readily available comparisons existed. In the practice of dialysis, water quality has always been of considerable importance. With the advent of widespread hemodialyzer reprocessing, the issues of water bacteriology and water quality have become more prominent."

Volume 5 of Contemporary Nephrology summarizes major advances in 15 different areas of nephrology. As in previous volumes the different chapters constitute up- of the discipline contributed by individuals dates in both basic and clinical aspects with in-depth expertise in their respective areas. We are grateful to the authors for their outstanding contributions to this fifth volume. Drs. Reuss and Cotton review in Chapter 1 new advances in our understanding of water transport in epithelial tissues responsive to antidiuretic hormone. In Chap- ters 2 and 3 Dr. Knox and Dr. Schoolwerth and their associates summarize respec- tively new information in the areas of renal hemodynamics and electrolyte excre- tion, and renal metabolism. Chapter 4, written by Drs. Laski and Kurtzman, updates recent developments in the regulation of acid-base balance in health and disease. Chapter 5, contributed by Drs. Sutton and Cameron, provides the reader with a detailed account of progress in the area of mineral metabolism. In Chapter 6, Dr. Campese examines the contribution of sodium, calcium, and neurogenic factors in the pathogenesis of essential hypertension. The immunological aspects of renal disease are clearly discussed by Dr. Couser in Chapter 7. New developments in this field are emphasized and should provide the reader with a clear understanding of the direction in which this field is moving. Drs. Humes and Messana (Chapter 8) discuss selected areas in which new developments have occurred in our understand- ing of acute renal failure and toxic nephropathy.

The year was 1943. As a third-year medical student at Stanford, I was about to witness the beginning of a medical miracle. Dr. Arthur Bloomfield, Professor of Medicine, had selected my patient, a middle aged man, who was dying of acute pneumococcal pneumonia, as one of the first patients to receive miniscule doses (by today's standards) of his meagre supply of a new drug - penicillin. The patient's response amazed everyone especially this impressionable medical student. The rest of the story is history. With one stroke, the introduction of penicillin removed from the medical scene the 'friend of the aged' - lobar pneumonia. The consequences, which no one could have imagined at the time, are still becoming manifest as other 'miracles' such as respirators, artificial kidneys and many potent new antibiotics have come upon the scene. All of us are aware that these miracles have created a variety of new challenges around the states of dying and near dying. We have no easy answers for these problems. Nevertheless as dialysis techniques, especially CAPD, are applied more widely to the treatment of the elderly, the task of helping the patient meet death with dignity becomes increasingly important and vexing because once begun, dialysis is difficult to terminate.