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.

A large number of chemical agents are known which affect blood and blood-forming organs. The purpose of this volume is to review the sig- nificant advances made over the past several years regarding such chemical agents. The purification, biological action, and therapeutic implications of several widely used hematopoietic growth factors such as interleukin 3 (IL-3 or multi-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), colony stimu- lating factor (CSF-I or M-CSF), thrombopoietin, and erythropoietin are included in this volume. These factors are important in regulating several hematopoietic cell lines such as neutrophils, monocytes, eosinophils, macrophages, megakaryocytes, platelets, and erythrocytes. People are exposed daily to numerous toxic chemical substances present in our environment which produce a suppression of erythropoiesis, myelo- poiesis, lymphocytopoiesis, and megakaryocytopoiesis. Attempts have been made in this volume to assess the therapeutic role of some of the hematopoietic factors such as erythropoietin in the anemia of end stage renal disease, as well as colony stimulating factors in other hematopoietic abnormalities. In addition, some of the chemical factors in our environment which suppress major hematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin I-alpha, interleukin I-beta, and interleukins 2, 3, 4, 5, 6, 7, and 9 are also included. An updating of the mechanism of action of each of these factors on the major hematopoietic lineages is covered.

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."

Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

One person in four in the industrialized countries suffers from hyperuricemia and is therefore at risk of developing gouty arthritis, nephrolithiasis, or any of the other consequences of urate deposition. At present, far too little is known about urate deposition and the mechanisms by which it occurs, as well as about its clinical consequences, which include formation of toph; over the helix of the ear or in bones close to joints that have never exhibited an attack, development of bursitis, chronic tendovaginitis leading to carpal tunnel syndrome, and gouty paraplegia. Information on these matters is needed to estimate the risks of hyperuricemia and to determine when therapeutic intervention is indicated. The contributions and discussions in this book, resulting from an international symposium held in December 1990 in the Medizinische Poliklinik in Munich, provide an up-to-date source of current knowledge about hyperuricemia in man and its clinical consequences.

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.

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.

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.

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."

In recent years both doctors and patients have become increasingly aware that many essential drugs may induce unfortunate side-effects in susceptible individuals. The kidney is the principal route of excretion for many of these substances and may as a result become involved in pathological processes. Developments in haemodialysis and haemo perfusion may be of value in increasing the rate of excretion of potentially toxic substances but it is essential that the advantages and disadvantages of these techniques are fully appreciated by all with an interest in clinical practice. This book details the recent advances in understanding of analgesic nephropathy, interstitial nephritis, elimination of poisons and drug monitoring. Each chapter has been written by a recognized expert in the field and provides information of relevance and practical import ance to the average clinician. The developments of the last decade have emphasized that drug toxicity is a subject on which all clinicians, but perhaps especially nephrologists, should be fully informed. ABOUT TH E EDITOR Professor Graeme R. D. Catto is Professor in Medicine and Thera peutics at the University of Aberdeen and Honorary Consultant Phy sician/Nephrologist to the Grampian Health Board. His current interest in transplant immunology was stimulated as a Harkness Fellow at Harvard Medicial School and the Peter Bent Brighton Hospital, Boston, USA. He is a member of many medical societies including the Association of Physicians of Great Britain and Ireland, the Renal Association and the Transplantation Society."

Blood pressure control is central to all bodily functions. There are many points in the multifaceted cybernetic system wherein hypertension may be produced. Hypertension is a 'young' disorder whose existence has been known for less than a century. It is not only extremely prevalent among every popula tion, but also deleterious to the health of mankind. The more we understand about hypertension's harmful effects, the more urgent is the need for its effective control. The kidney is the central organ that controls vascular tone and body fluid volume; these two factors are dominant in determining arterial blood pres sure. Hence, it is not surprising to find in hypertensive disorders that there are abnormalities in the kidneys, functional or anatomical, subtle or overt, that cause or are the consequence of hypertension. The first suggestion that the kidney could cause hypertension was made in 1836, before arterial pressure could even be measured, by Richard Bright. He observed that cardiac hypertrophy was often present in patients who died of renal disease. It was, however, Goldblatt and his colleagues in 1934 who opened the modern era of experimental and clinical research in renal hypertension. Since then, although far from complete, enthusiastic and intensive research efforts have greatly improved our understanding of the nature of renal hypertension."

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.

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."

Acute renal failure is undoubtedly one of the marize in one volume the recent advances on patho- most interesting and frequent syndromes observed physiology of acute renal failure, the clinical aspects by clinicians. A great number of factors may of the various forms (even those which have been acutely impair renal function, but the pathoge- disregarded in other surveys), the diagnostic tests netic mechanism by which this occurs is fre- available today in our clinical practice, the general quently unknown. Even the pathophysiology of and specific therapeutic measures and (very impor- ischaemic!toxic forms of acute renal failure re- tant, indeed), some useful suggestions for preven- mains controversial despite the huge number of tion. experimental and clinical studies. The contributors have provided clear, complete Medical management of patients with acute renal and up-to-date chapters. I am deeply grateful to failure has greatly improved in recent years, partic- them all. ularly with the use of different types of dialytic I like to express my sincere thanks to Dr. A.J.

The renewal of interest in peritoneal dialysis as a treatment modality for patients with end-stage renal disease was stimulated by the report of Po- povich and his colleagues in 1976 on the technique of CAPD. With the in- troduction of commercial dialysate-containing plastic bags, which mark- edly reduced the incidence of peritonitis, the use of CAPD as a primary treatment modality has increased significantly. At the present time, more than 12% of the patients undergoing dialysis in the United States are utiliz- ing CAPD; however, the use of CAPD among pediatric patients is con- siderably greater. The First International Symposium on CAPD in Children was orga- nized in order to gather together experts with experience in treating chil- dren undergoing CAPD in an attempt to exchange current information on the utilization of this emerging technique in children. Since pediatric pa- tients comprise a small percentage of the CAPD population and since lim- ited data were available concerning specific methodology and complica- tions of CAPD in children, it was hoped that an international symposium would provide a forum for an exchange of experience that would ultimate- ly lead to better adaptation and increased utilization of this technique.

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.

Renal function fails abruptly in a bewildering variety of clinical situations which lack any common clinical patterno This makes it impossible to define acute renal failure in the same way as heart failure or liver failureo Even oliguria, the commonest sign, is not invariably present. As a result, the detection of acute renal failure Table 1. Causes of acute renal failureo Acute tubular necrosis Ischaemic type Nephrotoxic type Cortical necrosi . * Hepatorenal syndrome Occlusion of main renal arteries Occlusion of arterioles Malignant hypertension Haemolytic uraemic syndrome Thrombotic thrombocytopenic purpura Postpartum nephrosclerosis Acute glomerulonephritis Post-streptococcal 'Crescentic' nephritis } do thO th t dO Necrotizing glomerulitis I IOpa IC WI sys emlc Iseases Renal vein thrombosis Obstruction U ric acid crystals Stones Tumours-benign and malignant Fibrosis Strictures 2 Acute and Chronic Renal Failure (ARF) depends on biochemical tests, which are fortunately simple to perform and are commonly available. However, the clinician has to think of the possibility in order to test the diagnosis. Frequently, patients are admitted to a renal unit from medical, surgical or gynaecological wards where the development of ARF has gone unrecognized, either because the relevant investigation has not been performed or because the result has been overlooked. This happens because ARF occurs in patients with complex problems which themselves demand con- siderable attention, and it is easy to overlook a comparatively rare, if important, complication.

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."