We are pleased to present to our readers the proeeedings of the Seeond Bari Seminars in Nephrology. The topie of theses proeeedings deals with elinieal and experimental aspeets of aeute renal failure. The Bari Seminars in Nephrology were initiated in 1984 and will be held every two years. It is attended by a large number of international elinieal seientists in the diseiplines of nephrology and related fields. The next Bari Seminars in Nephrology will take plaee dur i n g Ap r i 1 2 0 - 2 4 i n 1 988 'a n d t he t he m e 0 f t he ga t her i n g w i 1 1 be Drugs, Systemie Diseases and the Kidney. \\e are indebted for the generous finaneial support of the Centro Nazionale delle Rieherehe, Italy. Alberto Amerio Pasquale Coratelli Vito M. Campese Shaul G. Massry vii CONTENTS I. PATHOPHYSIOLOGY AND STRUCTURAL CHANGES OF ACUTE RENAL FAlLURE Pathogenesis of Acute Renal Failure 3 M. Burnier and R. W. Schrier Structural-Functional Correlates in Acute Renal Failure . . . . . . 15 G. Eknoyan, D. C. Dobyan, and R. E. Bulger Long Term Clinical and Morphological Evaluation of Acute Renal Failure . . . . . . 27 V. Bonomini, A. Vangelista, G. Frasca, S. Stefoni, M. P. Scolari, and G. Feliciangeli The Role of Renal Biopsy in Acute Renal Failure . . . . . . . . . . 35 G. D'Amico, G. Colasanti Catabolism in Acute Renal Failure: Importance of Glucocorticoids and Lysosomal Enzymes . . . . . 41 A. Heidland, R. M. Schaefer, J. Weipert, E."

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

There has been a growing awareness that nephrotoxicity represents a key factor in human nephropathies, where, irrespective of the causative agent, only a few clinical end-effects are diagnosed. Thus nephropathies are generally classified as acute or chronic renal failure, malignancies or immunological changes. The weaknesses in diagnosing nephropathies arises because of the effective role the kidney plays in maintaining homeostasis, despite the fact that it has been extensively damaged. The frequencies of some type of chemically-induced acute renal failure is well documented, but the causes of chronic renal failure, malignancy, and other nephropathies are far more difficult to associate with a chemical aetiology. Many of the new therapeutic agents have important beneficial effects, but they are found to have marked nephrotoxic effects. Thus there is a growing urgency to increase the stringency of chemical safety evaluation for their potential nephrotoxic effects. This is strongly countered by the increased financial pressure to identify potentially nephrotoxic chemicals earlier in their development and humanitarian considerations to more closely relate animal test to the clinical situation. Part of the challenge may be achieved by the increasing use of in vitro techniques.

Volume 4 of Contemporary Nephrology summarizes major advances in 16 different areas of nephrology during the years 1985 and 1986. Major changes in the composition of the Editorial Board and authorship of the different chapters have occurred in this volume. Six distinguished contributors have retired from the Editorial Board. They include Dr. Zalman A. Agus, Philadelphia; Dr. Robert Anderson, Denver; Dr. Eli Friedman, Brooklyn; Dr. Richard Glassock, Torrance, California; Dr. James Schafer, Birmingham, Alabama; and Dr. Gordon Williams, Bos ton. We are grateful to them for their outstanding contributions to the of this series and for their advice and suggestions as first three volumes members of the Editorial Board. They certainly deserve substantial credit for the success of this series. Seven outstanding academicians have joined the Board. They in clude Dr. Vito M. Campese, Professor of Medicine at the University of Southern California, who contributed the chapter on "Recent Advances in the Role of the Renal Nervous System and Renin in Hypertension"; Dr. William G. Couser, Professor of Medicine and Head of the Division of Nephrology at the University of Washington in Seattle ("Immunologic Aspects of Renal Disease"); Dr. Garabed Eknoyan, Professor of Medicine and Vice Chairman of the Department of Medicine at Baylor College of Medicine ("The Uremic Syndrome"); Dr. H. David Humes, Associate Professor of Medicine and Chief of the Nephrology Section at the Uni versity of Michigan Medical School, Veterans Administration Medical Center ("Acute Renal Failure and Toxic Nephropathy"); Dr."

LOUIS TOBIAN There are many reasons for suspecting that the medulla of the kidney is involved in the pathogenesis of hypertension. Although our present knowledge does not permit the assignment of a precise and exact role for the medulla, there are so many indications of its involvement that this is an appropriate time for the subject to be thoroughly reviewed, as Drs. MandaI and Bohman have done in this volume. The involvement of the renal medulla in hypertension was first strongly indicated by the studies of Eric Muirhead. Studying renoprival hyperten sion, he demonstrated that the injection of extracts of renal medulla could prevent this type of hypertension in the dog, rabbit, and rat. Subsequently, a number of experiments showed that implants of renal medulla could not only prevent renoprival hypertension but also greatly reduce the level of blood pressure in Goldblatt hypertension in the rat and rabbit. It was later noted that the majority of the surviving cells in these medullary implants were interstitial cells. Pitcock and Muirhead were able to culture these interstitial cells, and implants of the cultured cells lowered blood pressure in renoprival hypertension and Goldblatt hypertension, particularly in the rat. We were able to confirm these general observations by employing implants of medulla in "postsalt" hypertension. The medullary implants did indeed bring the blood pressure down."

Over the last few years, transplantation knowledge and techniques, as well as insights into pharmacology, have improved, thus enabling greater access to transplantation for patients. The pool of organs for transplantation is stable, and therefore insufficient to cope with the growing demand. To adjust demand and resources in the most equitable way, organ procurement and allocation have been organized nationally and often across borders. The national and international organ exchange programs were studied and discussed during the Congress on Organ Allocation, from which this book is derived. This book describes the state of the art in the management of waiting lists and the allocation of organs in transplantation. It includes chapters on the possibilities of expanding the pool of available cadaver organs. It also analyzes the results of transplantation of cadaver organs from older donors and marginal, non-heart beating donors. Transplantation policies based on the offering of organs by living donors are also described, as is the impact of delayed graft function on organ allocation.

Chronic renal disease has received increasing attention and concern since the passage in 1972 of PL 92-603, which provided coverage for end-stage renal disease (ESRD) treatment by the federal government. The human and economic costs of the ESRD program serve to emphasize the need to prevent or to arrest those diseases resulting in chronic renal failure, since none of the available treatments is without complications and/or side effects. The ESRD program, the only federal one that provides coverage for a catastrophic illness for almost the entire population (those qualifying under Social Security), cost almost $2 billion in 1983. The escalating costs of the ESRD program are attributed to the increasing number of patients requiring treatment and have focused concerns of the United States Government, both Congress and the administration, on ESRD. The National Institutes of Health (NIH), especially the Kidney, Urology, and Hematology Division of the National Institutes of Arthritis, Diabetes, and Digestive and Kidney Diseases (NIADDK), supports a sizable research program that bears on chronic renal disease and in association with this has sponsored many conferences and workshops on research on and causes and complications of chronic renal failure. This book is an outgrowth of the issues addressed by participants at a number of NIH conferences held in the 1980s.

Organ Shortage: The Solutions is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "

Professor David Kerr Royal Victoria Infirmary) Newcastle upon Tyne Do we need another book on renal disease? There are few small books, particularly from this side of the Atlantic, which provide a really sound foundation of renal physiology, biochemistry and immunology. For two decades "The Kidney" by Hugh de Wardener has given a splendid background in renal physiology but I doubt if any author has brought to this subject as wide an experience and knowledge of basic science as Dr Wardle possesses. His researches have ranged over haematology, the role of in travascular coagulation in acute renal failure, the biochemistry of uremic metabolites, the immunology of glomerulonephritis, to hyperlipidemia in the genesis of arterial disease. In all these topics he has mastered the laboratory techniques as well as studying the patients personally. He therefore has a unique opportunity to show how renal disease can be illuminated by an understanding of the pathogenetic mechanism and to point the way to future treatment more logical than the crude and empirical methods we use today. This approach should appeal particularly to the young graduate whose memory of biocht: mistry and physiology is still reasonably fresh."

In 1968 Drs. B. E. C. Nordin and A. Hodgkinson organized the First International Symposium on Urolithiasis Research in Leeds, England. One hundred and five participants from continental Europe, Great Britain, and the United States met to review their work and exchange ideas regarding the formation of urinary calculi. This meeting achieved several important goals. It pulled together a nidus of workers in the many scientific disciplines that relate to urolithiasis. This nidus served as the seed for research growth in a complex, interdisciplinary field. It established a forum for con tinuing communication in urolithiasis research with subsequent sym posia being held every 4 years. The Williamsburg Symposium was the fourth in the Leeds-Madrid Davos series involving 186 participants from throughout the world. A stated emphasis was on clinical research under way in the field. There were no invited speakers and for the first time the 41 papers that were presented orally at the meeting were selected from 184 submitted abstracts. A total of 134 papers were presented in the poster sessions in the afternoons where informal exchange between interested participants and investigators could occur without the restrictions of a plenary session. Virtually all areas of urolithi asis research from the most fundamental physical chemistry to clinical patterns of disease and specific modes of treatment were presented, reviewed and discussed during the meeting.

It must be considered that there is nothing more difficult to carry out, nor more doubtful of success, nor more dangerous to handle, than to initiate a new order of things. Machiavelli: The Prince (1513) These are the Proceedings of a Conference on Temperature and Environmental Factors and the Testis which took place at New York University School of Medicine, December 8th and 9th, 1989. There is good reason to believe that this was the first of its kind to address, exclusively, the implications of temperature for this highly thermosensitive organ and its precious genetic cargo. The organizers of the Conference hoped to stimulate interest in this area which, paradoxically, has a considerable literature but which has received scant attention and sometimes outright opposition from clinicians expert in male infertility. There have been studies of the relationship of temperature to reproduction starting in the mid-18th Century with observations of the relationship of water temperature to spawning of fish. There is also a vast literature on the deleterious effects of externally applied heat upon spermatogenesis but little study of the possibility that intrinsic heat may be an important etiologic factor in subfertile semen. Today, fertility research has largely ignored this in favor of research in areas which have not produced successes, in terms of live births, comparable to what can be obtained by varicocelectomy (when appropriate) or scrotal hypothermia: viz. 1. Concentration upon the endocrine aspects of testicular function and its relation to spermatogenesis.

The cause of end-stage renal failure in one-third of patients treated by regular haemodialysis or kidney transplantation is some variety of glomerular disease. Less serious glomerular dis orders are more common and often cause inappropriate conster nation to the patients and, sometimes, to their doctors. Similar clinical features can be produced by pathological lesions ranging from the trivial to the life-threatening, and renal biopsy is often necessary to establish the diagnosis. However, its widespread use during the past 20 years has enabled clinicopathological correlations to be made and the natural history of many 'glomerulopathies' to be established, though large areas of uncer tainty remain. In contrast to symptomatic measures, such as the management of uraemia or the nephrottc syndrome, the use of treatment in arresting the progress of the glomerular lesion itself is controver sial and is based on anecdotal evidence rather than controlled trials. Knowledge of the renal pathology will, at least, enable conditions in which immunosuppressive therapy is appropriate to be distinguished from those which are benign or self-limiting. In this book symptomatic management of the clinical syn dromes is detailed, but classification is firmly based on renal histological appearances. The relevance of immunofluorescent microscopy, ultrathin section examination and electron micros copy to our understanding of pathogenesis is described, as well as the uses of these techniques for morphological discrimination."

When Shaul Massry and Herbert Fleisch asked me to write a foreword for this book, I was honored and eagerly looked forward to reading the many chapters. As they came and I skimmed through them, my mind wandered back to the earliest classic contributions in this field in the late 1920s and early 1930s by Albright and his associates, Greenwald and Gross and Adolph, on the homeostatic regulation of inorganic phosphate and the central role of parathyroid hormone (PTH) in this regulation. They clearly showed the exquisite sensitivity of the renal handling of phosphate to varying dietary and parenteral loads and to changes in the level ofPTH. That two outstanding investigators in the field of divalent ion me tabolism should choose to edit a book solely about the renal handling of inorganic phosphate shows how far we have progressed from these early classics to the recent almost exponential increase in the research and publications related to this subject. Despite this increase, I asked myself, is such a large new monograph, consisting of 13 chapters and 30 distin guished authors, warranted? My reading of these chapters and my learning so much from them convinced me that it is, and my pride was heightened in being asked to write the foreword for this book."

The Fourth International Congress of Peritoneal Dialysis was held in Venice, Italy, June 29 to July 2, 1987. By this time peritoneal dialysis had emerged as a treatment for a substantial fraction of patients with end-stage renal disease and countless numbers of patients with acute renal failure. This treatment is now practiced worldwide and is the life-sustaining treatment for about 40,000 patients with chronic renal failure, representing 15 to 20% of dialysis therapy in about 1000 centers. It is not surprising, therefore, that the number of health professionals engaged in the investigation and the application of the treatment has also grown exponen tially. The First International Symposium on Peritoneal Dialysis, organized by Dr. A. Treviiio-Be cerra in Chapala, Mexico, in 1978, brought together a group of pioneers when continuous ambulatory peritoneal dialysis was in its infancy. In 1981, Dr. G. M. Gahl chaired the Second Symposium, in West Berlin, when the technique and professional interest were growing con siderably. By 1984, when Dr. 1. F. Winchester and I organized the Third Symposium, the pre sented papers exceeded 100 and there were about 1000 attendees. At that time, it was deemed appropriate to form a more organized group and the International Society for Peritoneal Dialy sis was founded. One of the first actions of the Society was to choose from among several applicants Dr."

The management of chronic renal failure by dialysis and transplantation has now become an established form of treatment in many parts of the world. However, these forms of treatment have brought with them problems in relation to the selection of patients, economics, clinical problems such as hypertension, encephalopathy, anaemia and renal bone disease, and psychological and social problems. The management of haemodialysis has changed over the years with developments in dialysers, vascular access and the duration of dialysis. Although the overall survival from renal trans plantation has changed little in the past four or five years, there are hopes of improvements in relation to tissue typing and enhancement. Perhaps the most important aspect in the management of chronic renal failure is the multi-disciplinary approach. Nursing and medical staff work closely with dialysis technicians, engineers, dietitians, local authority per sonnel, social workers and with the relatives of the patients. The symposium was planned to draw together representatives from all disciplines involved in the care of patients with chronic renal failure. One of the most relevant sessions was that in which two patients with chronic renal failure described their experience."

The kidney, similar to the heart, plays a three-fold role in essential hypertension. First, it participates in the patho genesis of arterial hypertension. Second, it suffers as a target organ of long-standing hypertension, and third, it experiences the effects of antihypertensive therapy. Perhaps most contested at the present time is the involvement of the kidney in the patho genesis of essential hypertension. More than a century ago, William Osler put forward three basic hypotheses about the "genuine contracted kidney. "l 1. "The hypertrophy can be regarded as an effect to overcome a sort of stop-cock action of the vessels when under the influence of an irritating ingredient in the blood greatly contracted and increased the peripheral resistance. " Clearly this hypothesis of an "irritating ingredient" is perhaps the most convincing nowadays, and numerous attempts have been made to identify a specific vasoconstrictive agent in the blood in essential hypertension. 2. "The obliteration of a large number of capillary territories in the kidney materially raised the arterial pressure. An additional factor of dimin ished excretion of water also heightened the pressure within the blood vessel. " Today we know that fluid volume overload in the presence of reduced renal mass seems to be the most likely mechanism accoun ting for renal parenchymal hypertension and, as shown by Guyton's group, for certain forms of experimental hypertension. 3.

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

In June, 1981, we conducted a two day international symposium in Rome devoted to original scientific presentations on arachidonic acid metabolism in the kidney. Scientists from 20 countries were represented either in the general scientific program or in the poster presentation. This book does not represent the proceedings of this international gathering, but rather the edited manuscripts specifically prepared as sum- maries of the scientific presentations. We feel that the timeliness and originality of the contributions as well as the need for a compilation of existing work on prosta- glandins, thromboxane, and the kidney warrant this publication. The meetings would have been impossible without the generous and substantial support of the Italian government, the National Institutes of Health, United States Public Health Service, and Merck Sharp & Dohme International. Supplementary support was also received from Ciba Geigy S. p. A. , Ente Fiuggi, Farmitalia Carlo Erba S. p. A. , Glaxo Laboratori S. p. A. , Hoechst Italia S. p. A. , Leo Pharmaceutical Products, Pfizer Italiana S. p. A. , Sigm? Tau S. p. A. , Squibb S. p. A. , The Upjohn Company, Wellcome Italia S. p. A. , and Burroughs Wellcome Company. The efficient organization of the symposium was largely attributable to the superb efforts of Elisabeth Mutschlechner and Miki Scarinci of C. K. International, Rome. Linda Goldberg provided expert and invaluable editorial and secretarial assistance in the organization of this book. The book is divided into four major sections comprising: I.

Im Juni 1979 hatte in Dusseldorf ein Symposion uber Diuretika stattgefunden. Behandelt wurden experimentelle und klinische Ergebnisse mit Diuretika, unter anderem mit Diucomb. Ziel des Symposions war, Untersuchungsergebnisse zu referieren und diskutieren. Teilnehmer waren Wissenschaft ler aus der Schweiz, Osterreich, Grossbritannien, USA und der Bundesrepublik Deutschland. Das Material dieses Symposions wurde uberarbeitet, Diskussionen durch einen Redaktionsstab gestrafft. Wir danken Frau J. BOROS fur wertvolle technische Assistenz. Der Springer-Verlag hat uns wiederum sach kundig beraten und ist in grosszugiger Weise unseren Wunschen entgegengekommen Die Herausgeber Inhaltsverzeichnis Einleitung. F. KRUCK . . . . . . . . . . . . . 1 1. Wirkungsmechanismen. Moderation: K. GREEFF . 3 Plasma Concentrations and Comparative Bioavailability of Bemetizide and Triamterene in Combination. L. F. CHASSEAUD . . . . . . . . 5 Pharmakokinetik von Diuretika bei eingeschrankter Nierenfunktion. H. KNAUF und E. MUTSCHLER 14 Diskussion 24 Neue Daten zur Toxizitat von Diuretika. F. LEUSCHNER 26 Diskussion 29 2. Renale Wirkungen. Moderation: O. KRAuPP. . . . . . . . . . . . 33 Die Wirkungsweise diuretischer Substanzen in Abhangigkeit von ihrer re- len Behandlung. P. DEETJEN . . . . . . . . . . . . . . . . . . . 35 Effects of Diuretics on Renal Potassium and Hydrogen Ion Transport. G. GIEBISCH and M. HROPOT . . . . . . . . . . . . . . . . . . . 42 Wirkungen von Diuretika auf den transzellularen Elektrolyttransport der Niere. M. WIEDERHOLT und L. L. HANsEN 53 Diskussion 60 Interaktion zwischen Diuretika und renalem Prostaglandinsystem. H. J. KRAMER, B. STINNESBECK, W. PRIOR und R. DUSING 64 71 Diskussion Untersuchungen zum Wirkungsmechanismus von Acetazolamid und SITS auf den Bikarbonattransport im proximalen Tubulus der Rattenniere."

Recent developments in recombinant DNA technology have led to the large-scale production of human erythropoietin and to the demonstration that it is effective in the treatment of renal and possibly some other anaemias. This has lent a new impetus to studies of the pathophysiology and pharmacology of the hormone which is reflected in this report of the proceedings of a meeting held in Liibeck in June 1988. In 15 papers, all from European centres, the broad topics covered are erythropoietin's physiology and chemistry, the patho- physiology of erythropoiesis and the use of erythropoietin in the treatment of anaemia. Several of the papers include up-to-date reviews of the literature. The field is now expanding rapidly, and this volume, though not comprehensive, usefully points up many areas of recent understanding as well as others of continuing un- certainty. Overall, it contains material likely to be of interest to biochemists and experimental haematologists as well as to phar- macologists, clinical haematologists and nephrologists.

Metabolic and electrolyte disorders can pose special challenges to physicians caring for the critically ill patients. Constrained by time and circumstances, clinicians require rapid access to information to help assess and manage these often life-threatening conditions. In this book, a readily useable road map is presented, emphasizing the interactions among problems and suggesting clear lines of action. Keeping the physiopathological mechanisms to the essential, and maintaining an uncluttered format, each chapter provides guidelines to understanding "how did we get here" and "what should we do now," as quickly and safely as possible. Chapters describe clinical presentation and management of the most common renal, electrolyte, acid-base, metabolic and endocrine disorders, complicating the course of critically ill patients.
Contributing authors are all experts in their respective fields, who regularly engage in the day-to-day management of critically ill patients. In a rapidly changing field, the authors have endeavored to maintain an updated approach, emphasizing the most recent evidence on diagnosis and management. Although controversy in the interpretation and management of some problems is inevitable, the editors see it as a desirable way to depict differing interpretations and solutions for each problem. Each chapter ends with a selected list of key references to facilitate in-depth review of each subject.
As with other titles in the Pittsburgh Critical Care Medicine series, this book is intended for frequent use by both "budding experts" as well as by seasoned practitioners in need for of quick and effective reference.

In one golden age of medicine epitomized by William Osler, the physician also aspired to mastery of gross and microscopic pathologic anatomy. Now another such age has dawned in which ultrastructure and immunopathology provide insights into mysterious diseases of the kidney, connective tissues, joints, and muscles, among other sites. Dr. Anil K. MandaI has a background in clinical nephrology, experimental pathology, and diagnostic pathology of renal diseases that suits him well for his chosen task. This is to explain clearly the clinicopathologic entities seen by nephrologists, using the full range of available morphologic techniques. His ap- proach is brisk and incisive. To read his monograph as a pathologist is to make oneself a better clinician, and as a physician is to improve one's grasp of pa- thology. Such correlative knowledge seems at present the means most likely to lead to the ultimate control of some crippling chronic renal diseases. Sheldon C. Sommers, M.D.

Nitrates have been for many years the cornerstone of cardiovascular therapy for various indications. Not only have nitrates stood the test of time for treatment of chronic stable angina pectoris, but the indications for them have markedly ex panded. They now include all forms of angina pectoris and myocardial ischemia, congestive heart failure and hypertensive emergencies. The beneficial effects of nitrates in all these conditions result from their vasodilatory properties, but it is still unclear whether the central or peripheral effects predominate in the thera peutic mechanism. Recently nitrates have been shown to fulfill the most important requirement for each and every drug - to reduce mortality. A large scale study revealed that isosorbide dinitrate, combined with hydralazine, reduced long-term mortality by 28% in patients with congestive heart failure. This finding will certainly stimulate research on nitrates, and it might be expected that interest in these drugs will markedly increase. The primarily used nitrates in clinical practice are nitroglycerin and the com plex organic nitrates, mainly isosorbide dinitrate. The organic mononitrates are now under clinical investigation, and isosorbide-5-mononitrate (IS-5-MN) appears to be especially promising.

The first International Symposium on Urolithiasis Research was held in Leeds, England, in 1968. The meeting was the first in what was to become a series of symposia intended to gather together a diverse group of biochemists and physicians, urologists and engineers, with a common interest in factors affecting the formation of human urinary stones. Since its inception the series has threaded a peripatetic course back and forth across the Atlantic Ocean, from Madrid in Spain, to Davos in Switzerland, to Williamsburg in the USA, to Garmisch-Partenkirchen in Germany and Vancouver in Canada, under the guardianship of Drs Nordin, Cifuentes Delatte, Fleisch, Smith, Schwille, Dirks and Sutton, and their colleagues. In 1992, for the first time, the meeting moved to the southern hemisphere, to Cairns in Northeastern Australia. Unlike most previous symposia, there were no invited papers. Instead, the submitted abstracts were allowed to dictate the content of the meeting so that the conference programme would reflect the flavour of current research in the field. To achieve this, all abstracts were graded anonymously by three referees to determine their categorization as oral, theme poster, or general poster presentations. The 300 or so accepted absracts were then allocated to seven plenary sessions, nine theme poster discus sion groups and three large general poster sessions."

In all varieties of organ transplants, early results have dramatically improved over the past two decades and failures due to acute rejection are becoming rarer. Efficient immunosuppressive regimens have been developed with the objective of very good results at 1, 3 and 5 years. Successful transplants, however, are significantly less frequent at 10 and 20 years, and many patients require retransplantation. Many factors are involved in late graft loss and it is now well recognized that, in addition to chronic rejection, a number of non-immunologic factors play a prominent role. In the case of renal transplantation, a reduced mass loss (transplantation of a single kidney, sometimes from an aged donor, ischemic injury and alteration of some nephrons in the case of early acute rejection) will result in slowly progressing chronic renal failure, even in the absence of any supplementary attack of an immunological nature. The new treatments must be analyzed in the light of their capacity to reduce these late failures. Several preventive measures can also limit both immunologic and non-immunologic factors of late transplant deterioration.