These proceedings of the 5th Prouts Neck Meeting on Prostate Cancer, held in October, 1989, highlight the many advances in the understanding of prostatic growth and function at the cellular and molecular levels which have been registered since the first Prouts Neck Meeting in 1985, a meeting which also focused on the then current concepts and basic approaches to understanding prostate cancer. Inter vening Prouts Neck Meetings in 1986, 1987 and 1988 were devoted to treatment, image cytometry and clinical markers. As before, the Prouts Neck tradition of bringing together an international, multidiscipli nary group of experts for 3 days to exchange ideas and new data, in the relaxed atmosphere of an old iun on the scenic Maine coast, proved to be an ideal combination for a highly successful conference. Accordingly, the Organ System Program of the National Cancer Institute plans to use the Prouts Neck model for future conferences on other solid tumors (bladder in 1990 and kidney in 1991) and will return to the prostate in 1992. A new dimension was added to the current program through the inclusion of a poster session to recognize the research of pre-and postdoctoral investigators. The posters were judged by Drs. Collette Freeman, Frank French, Shutsung Liao, Robert Matusik and Henry Sun. The three winners, in alphabeti cal order, were John Fabian, Robert Getzenberg and Ming Fong-Lin."

Volume 2 of Contnnporary Xephrology updates the major developments which ha\'e occurred during the past 2 years in 15 major areas of both basic and clinical nephrology. In addition, this volume has a section, Chapter 8, \uitten by Drs. Pederson, Llach, and Papper, from the Med- ical School at the Universitv of Oklahoma, which reviews the recent developments on nonilwasive diagnostic techniques in nephrology. The other chapters are presented in such a way as to emphasize the major advances that have occurred in the different areas in the last 2 years. In Chapter 1, Dr. Schafer analyzes in detail the new information available regarding the action of aldosterone both in anuran membranes and in the mammalian kidney. Drs. Knox and Romero, in Chapter 2, update the information accrued du ring the last 2 years in the area of renal hemodynamics and sodium chloride excretion. In the area of renal me- tabolism (Chapter 3), Schoolwerth, Little, and Idell-Wenger review in detail the metabolism of lipids in the kidney and its potential relation to renal function. This is, to the best of our knowledge, the first compre- hensive review of this subject in any textbook of nephrology. Dr. Dunn provides an authoritative review of the major advances in the rapidly expanding field of prostaglandins with particular emphasis on renal prostaglandins (Chapter 4). Drs. Batlle and Kurtzman update new con- cepts of acid-base phvsiology and pathophysiology, and Dr.

Immunosuppression in solid organ transplantation is currently experiencing a worldwide revival since new drugs are now available and others are under development. In order to contribute to the design of future strategies, a critical approach of surrogate endpoints is given and long-term side effects are analysed, together with the impact of non-compliance, quality-of-life and economical parameters. In this book, international specialists have set up the scientific rationale and provided new bases for further immunosuppressive strategies.

This book, the proceedings of the 32nd International Conference on Transplantation and Clinical Immunology, held in Lyon, France, on May 25-26, 2000, addresses novel issues in terms of changing indications for transplantation in the management of organ failure, whether humans will remain the only source for organ procurement, prospects for engineering in organ replacement, and whether transplantation will remain the most appropriate approach to organ failure. Some promising treatments are approached, such as enzymic and biochemical replacement, gene therapy, tolerance induction, stem cell transplantation, and xenotransplantation. In addition to the constant improvement in conservative management of organ failure in general, ongoing research in selected fields is reported in the proceedings, such as liver transplantation vs artificial liver, novel dialysis strategies vs evolving immunosuppression in kidney transplantation, islets transplantation and external implantable insulin pumps vs pancreas transplantation in diabetic patients, circulatory assistance and intramyocardial myoblast injection vs heart transplantation. Pivotal experience in selected emerging transplantations is included, that is, small bowel, limb, skin and neuronal transplantation. Such fascinating perspectives raise medical, economical, and ethical problems which are discussed in this book.

After a decade or longer, approximately one-third of individuals with either type 1 or type 2 diabetes commence a downhill course in which decreasing renal function and failing vision define a Renal-Retinal Syndrome, dominating all aspects of life and presaging early death. Only a generation ago, survival after onset of end-stage renal disease (ESRD) in diabetes was limited because rehabilitation was preempted by blindness, limb amputation, stroke, and heart disease. By 1998, however, team management has improved the outlook, with preserved sight and return to work and home responsibilities, usually for a decade or longer, following kidney transplantation and laser photocoagulation. Recognition of the critical requirement for blood pressure regulation and metabolic control are central themes in management. In this unique book, the accomplishments of ophthalmologists, nephrologists, diabetologists, transplant surgeons, and basic scientists are blended into a strategic approach that may be readily applied by all those caring for diabetic patients. Each of twenty-one presentations suitable for primary care physicians, as well as for subspecialists concerned with macrovascular and microvascular complications of diabetes, is placed in perspective by an introductory editorial analysis. Promising near-term innovative therapies, including insertion of genetically engineered beta cells or polymer-coated islets of Langerhans, interdiction of kinins that promote retinal angiogenesis, and prevention of synthesis of advanced glycosylated endproducts (AGEs), are presented in detail. While comprehensive care of diabetic patients reflects multiple incremental advances that in sum afford major benefit, this text envisions further remarkable changes likely to suppress and possibly entirely prevent the Diabetic Renal-Retinal Syndrome.

The contents of this book represent papers which were presented at the Third International Meeting on "Side-Effects of Anti-Inflammatory and Analgesic Drugs" which was held under the auspices of the University of Verona, Institute of Pharmacology in Verona on 8-11 May 1991. This meeting was held in conjunction with the 13th European Workshop on Inflammation and although publications from this part of the meeting are not published here (they appear in Agents and Actions), we were fortunate in having a group of people interested in inflammation from varying backgrounds. The success of the third meeting followed previous meetings held in Cambridge and Verona respectively and continue a tradition which has now become well established. The meeting brought together physicians, scientists and those concerned with the production and use of anti-inflammatory drugs to a very stimulating conference to discuss basic issues affecting all aspects of side-effects of anti-inflammatory and analgesic drugs as well as their detection and treatment. The meeting was held in the Auditorium of Glaxo Italy and we are very grateful to that company for use of their facilities as well as to the University of Verona, Institute of Pharmacology, for valuable secretarial and administrative help. The success of the conference would not have been possible without valuable financial assistance of the companies listed separately (under Acknowledgements) as well as to the organizers of the 13th European Workshop on Inflammation who collaborated with us.

Although it has been appreciated for many years that immune processes underlie most types of glomerulonephritis, it is the recent explosion in knowl edge of cellular and molecular immunology that has prompted another book on the subject. The understanding of the mechanisms involved in renal injury requires the integration of information from in vitro cell-culture systems, experimental models of disease, and clinical studies. This volume draws on all of these sources in an attempt to explain current concepts of nephritis. Increased emphasis is placed on autoimmune processes, as opposed to the deposition of circulating immune complexes, although it will be apparent that these may overlap in the area of "in situ" immune complex formation. Of central importance in autoimmunity is the relationship between antigen pre senting cells (including B cells) expressing MHC class II molecules, autoan tigenic peptides, T helper lymphocytes, and various effector cells. The mechanisms by which the immune system may lead to tissue injury are also becoming better understood, and consideration is given to the role of inflam matory cells, the complement proteins, and soluble factors such as cytokines and eicosanoids."

The last twenty years has seen the biggest revolution in the treatment of renal tract stone that has ever been experienced in the history of urolithiasis. The treatment of upper tract renal stone has progressed from the days of a very traumatic and morbid procedure to the relatively innocuous, walk in/walk out therapy of extracorporeal lithotripsy. This progression of events has resulted in a complete reappraisal of management of all types of urinary calculi. From an initial reluctance to treat many stones because of the trauma involved, we have now passed to a situation where smaller and asympto matic stones may be pre-emptively treated before the treatment of serious clinical problems. It is true to say that in Westemized societies the problem of urolithiasis has almost completely been solved by the advent of advanced technology. In this volume, attention is drawn to the fact that there are still persistent difficulties in treating urolithiasis in the less developed and less affluent societies. The differences in epidemiology of urolithiasis in various areas of the world are highlighted, noting a rapid decrease in the incidence of bladder calculi in impover ished areas where affluence increases. Coupled with this progression of affluence however is the well documented increase in the incidence of upper tract renal stones of oxalate nature. This scenario has been almost universal across all coun tries in the last few decades.

Death on Hemodialysis: Preventable or Inevitable? presents the transactions of the Brooklyn meeting, held in April 1993, including an analysis by Scribner and Schreiner and an introduction by Edmund Bourke. Authors include the heads of dialysis registries for Japan, Europe, and the United States, as well as protagonists of dialyser reuse and short dialysis times. Enthusiasts championed the determination of adequacy of dialysis by formulae or by clinical assessment. All chapters are direct and forceful. The reader will be able to judge the data on what are key controversies in planning dialysis protocols and schedules.

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

Because of many advances in medicine and biotechnology, an increasing number of individuals are surviving into old age, and we are now challenged to apply sophisticated medical knowledge to the care of the elderly citizen. In nephrology, individuals older than 65 are the fastest-growing group of patients requiring dialysis. Similarly, in increasing numbers, elderly persons present themselves with renal complaints to their family doctor, the geriatrician or the nephrologist. In August 1998, with the financial support of the John A. Hartford Foundation, leaders in geriatrics, nephrology and urology met in Jasper, Alberta, for one week to discuss their areas of special knowledge and to learn from each other. Geriatricians learned from nephrologists, nephrologists learned from geriatricians, and both came to see that they had much in common. All participants discovered a common interest, challenge and commitment, namely, to provide the best renal care to a progressively aging population and to teach their fellows the principles of the other collaborating specialties. This book contains all the papers presented at this meeting and also the text of group discussions on Training and Education, Special Clinical Problems in Geriatric Patients, and Recommendations in Basic and Clinical Research. Nephrology and Geriatrics Integrated will prove useful to both nephrologists and geriatricians in their efforts to manage the renal complaints of the elderly, who come to them in increasing numbers.

This conference and monograph were the result of many collective efforts. The whole concept was formulated one early Wednesday morning at our weekly research meeting at Children's Hospital in our division of urology. We have been most fortunate to have a close collaboration with Bob Levin, Ed Macarak, and Pam Howard who have helped steer the course of our division's growing interest in basic science. At our weekly meetings our laboratory fellow will summarize their current work. Other ongoing areas of investigation in our labs and elsewhere are discussed. We have always made an effort to try and understand what other groups are doing who are working in the area of bladder smooth muscle research. It occurred to us that the best way to really know what everyone working in this field was doing would be to sponsor a 2-day meeting where we could all gather to discuss our ongoing work. A major limitation of the annual meeting of the American Urologic Association or the urology section of the American Academy of Pediatrics is that the scientfic sessions are limited as these are meant to be primarily clinical meetings (as they should be). For this reason the idea of a meeting devoted solely to research about the urinary bladder had great appeal. In addition to allowing for longer presentations than the standard 5 to 7 minutes, every effort would be made to encourage a dialogue amongst the presenters and the audience.

This book examines renal disease from an immunological perspective; it has been designed to be suitable both as an introductory overview of the area, as well as a guide to further reading. Following an introductory chapter, which discusses general immunological principles of particular relevance to autoimmunity and immunological mechanisms of renal injury, each of the major forms of renal disease with a significant immunopathogenesis is considered. The immunogenetics of each condition is reviewed, followed by a discussion of the immunopathology in animal models and in human disease. A section on therapeutic aspects of immunological relevance is followed by a concluding section which contains more speculative material. A final chapter summarises the various therapeutic strategies available. The volume is suitable for consultants and clinicians in training, particularly in the areas of nephrology and immunology, and for basic scientists working on relevant animal models, autoimmunity and renal disease.

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

"Endourology" provides a summary of the different endourological modalitites, especially the more advanced and controversial techniques, such as the antegrade resection of urethral valves, the transperineal I 125 seed implanations, the spoonloop resectoscope, flexible endoscopy, teflon injection to correct vesicoureteral reflux, stone manipulation in calyceal diverticula, as well as the extraperitoneal pelvioscopy. These techniques are supported by descriptions of the standard endourological procedures.

The presence of Chronic Kidney Disease (CKD) increases the risk of death from cardiovascular causes and makes the management of heart failure difficult. The coexistence of CKD and heart failure is increasing in prevalence worldwide and requires a unique and subtle approach to patient management. Managing the Kidney in Heart Failure focuses on the therapeutic management of cardio renal patients. Common heart and kidney failure conditions are presented along with treatment scenarios aimed to reduce cardiovascular mortality and preserve kidney function. Co-authored by a Nephrologist and Cardiologist, each chapter of this concise and practical handbook offers a unified perspective to these chronic conditions.

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.

Bladder Cancer is designed for researchers and clinicians involved in urologic practice, including urologists, medical oncologists, pathologists and radiologists. It provides comprehensive guidance for treating and understanding bladder cancer and serves as an up-to-date reference reflecting evidence-based research. The biological behavior of this disease entity shows a heterogeneous pattern with diverse morbidity and mortality depending on a variety of factors, such as tumor characteristics (tumor stage, grade, size, number, shape, and histologic subtypes) and applied treatment modalities (surgery or non-surgical management). This book presents the substantial academic developments in the field of bladder cancer in one convenient reference.

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."

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."

The master tool of logic is the syllogism. If A> Band B> C, then it must follow as the night the day that A > C. If the major and minor premises are true or scientifically correct by current knowledge, the conclusion is true or at least scientifically correct by current knowledge. The demographer of today beams a clear message, which if not true is at least scientifically correct by current knowledge. In the first 80 years of the Twentieth Century, the 'over-65' population of Americans increased eight fold. By century's end it will have increased 12-fold and shortly thereafter will include one in five Americans. While initially a fact of the developed world, the pace of similar graying is accelerating even more rapidly in the Second and Third Worlds. This gray delta constitutes about 35 million living Americans, who may use one-half or more of the health care resources. A would have to be a lot more foolish than B if they failed to recognize that in the coming decade the causation, case-mix, and area of the gray delta demands a change from early, mid-or even later-century medicine. If Homer Smith was right in saying, "We are what we are because we have the kind of kidneys we have" and "The kidneys make the stuff of philosophy", then the who, what, where, when, and why the gray delta will be cared for must focus on the stuff of geriatric nephrology.

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.

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.

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."