The previous volume on Antihypertensive Agents in the Handbook of Experi mental Pharmacology, published in 1977, was edited by the late Franz Gross from the Department of Pharmacology in Heidelberg, who was one of the grand old men in hypertension research. Now, more than 10 years later, it is necessary to update this volume. From the early days of antihypertensive drug treatment, starting about 30 years ago with drugs such as reserpine and guanethidine, the pharmacology of cardiovas" cular therapy has evolved into a highly sophisticated and effective therapeutic regimen. The major breakthroughs in the 1960s were the introduction of diuretics and beta-blockers. Then, in the 1980s, came the calcium antagonists and con verting enzyme inhibitors. It can be anticipated that the next decade will see a further expansion and sophistication of blood pressure lowering drugs. This book provides a state-of-the-art discussion of chemical, experimental, and clinical pharmacological data as well as of practical experience with drugs which are presently being used or which are going to be introduced on the market in the near future. The purpose of this volume is to provide a complete discussion of antihypertensive agents. Each major class of antihypertensive drugs is treated exhaustively in a separate chapter, fully referenced with chemical formulae, and richly illustrated with figures and tables. International authorities were asked to contribute in their respective fields of expertise."

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."

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."

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.

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.

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."

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.

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.

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."

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."

This book in the Topic Pack series covers some of the commoner and some of the rarer nephrological diseases. Owing to their diverse nature a 'traditional' approach, i.e. one considering pathogenesis, symptoms, signs and treatment, has been used. This inevitably leads to some repetition but the reader should be con stantly reminded that apparently trivial symptoms such as fre quency, dysuria, etc. may be the clues to more fascinating pathol ogy. In addition, where relevant, attempts have been made to remind the reader of some basic renal physiology in order to understand the results of pathological changes, those changes being illustrated by renal histology, specimens and radiographs. John Walls, Leicester General Hospital, 1. Urinary Tract Infections Infection of the urinary tract is the commonest renal disease seen in nephrological practice and second only to infections of the respiratory tract in overall clinical practice. With the widespread and early use of antibiotics over the past three decades it was hoped that some of the problems caused by urinary tract infec tions would be eliminated. However, this has not proved so, as the figures from the European Dialysis and Transplant Association Register (1975) have shown (Figure 1). 'Pyelonephritis' is the Figure 1. The main causes of end stage renal failure (from the European Dialysis and Transplant Association Register 1975)."

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.

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."