We have witnessed a rapid development within the field of the kidney and hypertension in diabetes mellitus. A significant amount of work within the traditional areas has been published, and several new dimensions are now being developed, mostly in the experimental setting. These dimensions are discussed in several chapters of this new edition, The Kidney and Hypertension in Diabetes Mellitus, Fourth Edition. This volume endeavors to cover all aspects of renal involvement in diabetes. It is written by colleagues who are themselves active in the many fields of medical research covered in this volume: epidemiology, physiology and pathophysiology, laboratory methodology and renal pathology.

The first sporadic observations describing renal abnormalities in diabetes were published late in the 19th century, but systematic studies of the kidney in diabetes started only half a century ago after the paper by Cambier in 1934 and the much more famous study by Kimmelstiel and Wilson in 1936. These authors described two distinct features of renal involvement in diabetes: early hyperfiltration and late nephropathy. Diabetic nephropathy is, despite half a century of studies, still a very pertinent problem, renal disease in diabetes now being a very common cause of end-stage renal failure in Europe and North America and probably throughout the world. It is a very important part of the generalized vascular disease found in long-term diabetes as described by Knud Lundbaek in his mono graph Long-term Diabetes in 1953, published by Munks gaard, Copenhagen. Surprisingly, there has not been a comprehensive volume describing all aspects of renal involvement in diabetes, and the time is now ripe for such a volume summarizing the very considerable research activity within this field during the last decade and especially during the last few years. This book attempts to cover practically all aspects of renal involvement in diabetes. It is written by colleagues who are themselves active in the many fields of medical research covered in this volume: epidemiology, physiology and pathophysiology, laboratory methodology, and renal pathology. New studies deal with the dia gnosis and treatment of both incipient and overt nephropathy by metabolie, antihypertensive, and dietary invention."

Renal sonography forms a basic part of routine diagnostic strategy. This textbook summarizes eighteen years of experience in diagnostic ultrasound. We want it to serve as a guide to both imagers and mere consumers of information. That is why we shall emphasize practical advice and diagnostic pitfalls; it is also why we shall often deal with the relations of sonography with other diagnostic procedures, which it may complement or replace, precede or follow, the purpose being to achieve efficiency at low cost. We shall limit our subject matter to the kidney itself and the neighboring retroperitoneal compartments, dealing only briefly with the lower urinary tract, which requires specialized procedures. We devoted considerable space to renal sonography in our book Clinical Atlas of Ultrasonic Radiography, published in 1973. Since then, nothing has changed and everything has changed. Nothing, because even then the differential diagnosis between a solid and a cystic mass, the etiologic diagnosis of a nonsecreting kidney, and the positive diagnosis of a traumatic juxtarenal hematoma were quite reliable, making possible drastic reductions in the indications for instrumental roentgenologic examinations. Everything, be cause improved resolution and grey scale imaging (already partially achieved in 1973, thanks to real time) have profoundly refined both anatomic and pathologic ultrasonic studies. And now high resolution real time imaging has revolutionized renal examination techniques, whereas Doppler is entering routine ultrasonic diagnosis."

There is a rapid increase in interest related to novel approaches in artificial kidneys, artificial liver, and detoxifi cation. Recent research has included the successful clinical appli cations of the principle of artificial cells for adsorbent hemo perfusion. Since it is 20 years ago at McGill that the first report on "Artificial Cells" was presented, I thought it might be useful to get together a small group of speakers and participants for a day before the ASAIO meeting to discuss some recent advances in the area of the clinical applications of artificial kidney, artificial liver and artificial cells with emphasis on adsorbent hemoperfusion. However, the enthusiastic supports of distinguished speakers, session chairmen and participants were such that the original pro jection of 100 participants had expanded to a preregistration total of 250, from Australia, Canada, England, France, Germany, Israel, Italy, Japan, The Netherlands, Scotland, Sweden and U. S. A. The program also expanded to include a review section on hemodialysis, dialysate regeneration, hemofiltration, resin hemoperfusion and oxystarch given by their respective originators. The remaining of the symposium emphasizes the status of the art on different encap sulated adsorbent hemoperfusion approaches. I would like to apolo gize to those who we could not accommodate beca se of space limita tions. It is hoped that this symposium volume may be useful for them and for others who are interested in this area. Special thanks are due to Ms Joanne Toms for her excellent secretarial assistance for the conference and Mrs."

The general populations are incidentally exposed to a wide variety of xenobiotics as a consequence of the pollution of the environment by industrial and agricultural chemicals. Xenobiotics entering the animal will undergo one or more of the following fate: (a) elimination unchanged, (b) metabolism by enzymes, (c) spontaneous chemical transformation and (d) remain unchanged in the body. The actions of xenobiotics on the body exhibit certain specificity depending upon the compound's chemical structure and reactivity. Since the processes of metabolism change these chemical properties ofaxenobiotic, bewildering number of reactions continue to pose new challenges to toxicologists and pharmacologists. It necessitates periodic and precise revision of the subject. This book contains invited contributions from learned colleagues that offer an excellent survey of and profound insight into the disposition and metabolism of a few environmentally and industrially significant xenobiotics. The topics range from an assessment of drug metabolising enzymes in the liver, DNA damage by reactive oxygen species generated by pesticides, role of NO in liver injury, hepatotrophicgrowth factor in liver regeneration, extracellular matrix in the liver, oncogene expression in liver injury, the hepatocarcinogenesis to oxidative stress and undifferentiated gene expression. Detailed analysis of the validity of liver function tests has been included. Last Chapter addresses the problem of apoptosis, which plays a key role in the signal transduction system of xenobiotics-induced liver injury. The reader should appreciate that overall exposure to this field is expanding at a rapid pace and selections had to be made.

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.

This book is intended as a practical bench manual phological abnormalities in renal diseases, and for the hospital pathologist who wishes to have where appropriate these have been illustrated. access to a simple informative account of renal Although the main emphasis is on the pathology, pathology, particularly for the interpretation of the relevant clinical aspects of the conditions cov percutaneous needle biopsy specimens. I n addition ered are included in recognition of the fact that we trust it will be valuable to physicians working renal disease is an area in which correlation of the in the field of renal disease, for whom the interpre clinical and histopathological findings is particularly tation of renal biopsy material is directly relevant to important in reaching an informed diagnosis. patient management. Whilst a comprehensive coverage more appro priate to a larger text has not been attempted, the Acknowledgements text has been planned to give an adequate account of the more important non-neoplastic disease pro We would like to thank the technical staff of the cesses and their pathological appearances in the Histopathology Laboratories of The London Hos kidney. Points of difficulty in interpretation and dif pital Medical College, The Hospital for Sick Chil ferential diagnosis are covered both in the text and in dren, Great Ormond Street, and Guy's Hospital the illustrations.

Infectious and non-infectious tubulointerstitial nephropathies are old subjects but there is enough confusion and disagreement on terminology and etiopathogenesis to warrant a new look at these problems. We were fortunate in having at the Pediatric Nephrology Seminar 6 and as contributors to this volume, the representative- or shall I say "originators"? - of each of the three most identifi- able positions: Dr. Renee Habib - congenital anomalies, Dr. John Hodson - reflux, and Dr. Robert Heptinstall - infection. Although some tend to hold onto one position and exclude others, in this case there was overlapping of perception. Dr. Habib accepts a role for infection in reflux and for infection in the presence of obstruc- tion; Dr. Hodson accepts infection and congenital anomalies as modi- fiers; and Dr. Heptinstall takes an overall position whicm encompas- ses the three. Thus the first part of the book emphasizes the complexity of something as seemingly simple as UTI and demonstrates awareness of disagreement even among the pros about meanings, interpretations, and treatment. Drs. Gustavo Gordillo, Jorge de la Cruz and their associates emphasize the importance of predisposing factors for UTI; Dr. Materson focuses on the workup of the patient, Dr. Zillerueloon bacteriological aspects, and Dr. Gorman on treatment approaches. Dr. Vaamonde reviews nephrotoxic agents. Finally, Drs. Andres and Noble review the immunological aspects of various tubulointer- stitial nephritides.

We are pleased to present to our readers the Proceedings of the Fifth International Workshop on Phosphate and Other Minerals which was held in New York City, New York, U.S.A during September 23-27,1981. It was hosted by Joseph M. Letteri, M.D., Professor of Medicine at the State University of New York at Stonybrook School of Medicine, and Chief, Division of Nephrology, Nassau County Medical Center. As in the previous Workshops, this meeting provided an oppor tunity for interested scientists from interrelated fields, including nephrology, endocrinology, physiology, biochemistry and nutrition, to get together and discuss the recent advances in the field of phosphate and mineral metabolism. There were 29 invited presenta tions by leading scientists and 40 oral and 90 poster presentations selected from over 250 abstracts submitted to the Organizing Committee. The Workshop was attended by 250 scientists from 14 countries including Austria, Australia, Canada, Denmark, England, France, Germany, Holland, Israel, Italy, Japan, Sweden, and the United States of America. The Sixth International Workshop on Phosphate and Other Minerals will be held during June 24-26, 1983 in Verona, Italy. It will be hosted by Professor Giuseppe Maschio, Director, Division of Nephrology, Istituti Ospitalieri, Verona, Italy. The theme of this coming Workshop will continue to focus on the pathophysiology of phosphate homeostasis and the metabolism of other minerals."

With a long practice of organ transplantation, retransplantation has become a major goal in patients with long-term failure of their first transplant (chronic rejection, exhaustion of the transplant, recurrence of the initial disease, etc. ). In addition, retransplantation can be necessary in the initial period, due to severe acute rejection, a non-functioning organ, or surgical complication. Immunological and non-immunological factors affecting the success of a second transplant are described in this volume, together with alternatives to retransplantation. It is hoped that in the future retransplants will be less frequent, as a result of improved prevention of transplant failure. J. L. Torrroine et a/. (ens. ), Retra isplantation, xvii. Q 1997 Kluwer Academic Pirblislters. P . iilted in Great Britain. List of contributors R. ARNOLD Y. W. CHO University of Pittsburgh UCLA School of Medicine Center for Medical Ethics Tissue Typing Laboratory Division of General Internal Medicine 950 Veteran Avenue 200 Lothrop Street - MUH, Suite W-919 Los Angeles, CA 90095-1652 Pittsburgh, PA 15213-2582 USA USA P. COCHAT M. A. BELGER Hopital Edouard Herriot UKTSSA Pavillon S Fox Den Road 5, Place d'Arsonva1 Stoke Gifford F-69437 Lyon Cedex 3 Bristol BS12 5RR France UK B. CUZIN F. BERTHOUX Hopital Edouard Herriot Service de Nephrologie et Pavillon V Transplantation Renale 5, Place d3Arsonval Hopital Nord F-69437 Lyon Cedex 3 F-42055 Saint Etienne Cedex 2 France France J. H. DAUBER C.

We are pleased to present to our readers the Proceedings of the Third International Workshop on Phosphate and Other Minerals which was held in Madrid, during July 15-18, 1977. It was hosted by Dr. Aurelio Rapado, Head of the Metabolic Unit at the Fundacion Jimenez Diaz. The Third International Workshop was organized in the tradition of the previous two Workshops. Scientists from 15 countries attended the meeting which provided a forum for formal presentations and informal discussions of topics of current interest in the field of phosphate metabolism, and that of the homeostasis of other minerals. One day of the Workshop was devoted to the subject of Phosphate Depletion. The latest information on the various aspects of the metabolic consequences of phosphate depletion were brought into focus. In the preface of the Proceedings of the Second International Workshop on Phosphate, we indicated that the enthusiasm with which these Workshops were received generated the idea for the creation of a Journal which will publish research endeavors related to mineral and electrolyte metabolism. These efforts were brought into fruition, and the first issue of the new Journal, M). . neJLai. . and E-te. c. ;tJr. o-ty-te. Me. -taboWm has already appeared in November, 1977. It is published by Karger of Basel, Switzerland under the Editorship of Dr. Shaul G. Massry of Los Angeles, with Dr. Louis V. Avioli of St. Louis and Dr. Eberhard Ritz of Heidelberg, serving as Associate Editors.

We are pleased to present to our readers the Proceedings of the Sixth International Workshop on Phosphate and Other Minerals which was held in Verona, Italy, during June 24-26, 1983. It was hosted by Professor Giuseppe Maschio, Professor of Medicine and Chief, Department of Nephrology at the University of Verona. The Sixth Workshop maintained the tradition of the previous ones. It provided a unique and outstanding opportunity for close interaction between scientist involved in the research of the overall field of Mineral Metabolism. The current Workshop was attended by 250 scientists from 15 countries including Austria, Canada, Denmark, England, France, Germany, Holland, Israel, Italy, Japan, Spain, Sweden, Switzerland, and the United States of America. The topics discussed included the renal handling of phosphate, transport of other minerals, intestinal absorption of calcium and phosphate and phosphate homeostasis in health and disease. Two symposia dealing with the recent developments of the interactions between minerals, parathyroid hormone, and blood pressure and between minerals and myopathies were included. In addition to the 15 State-of-the-Art Lectures, there were 43 oral and 63 poster presentations selected from over 200 abstracts sub mitted to the Program Committee. The Seventh International Workshop on Phosphate and Other Minerals will be held during September, 1985, in Marseille, France. It will be hosted by Professor Michel almer, Chief of the Department of Nephrology at the University of Marseille. The theme of this coming Workshop will focus on the pathophysiology of phosphate homeostasis and the metabolism of other minerals."

We are pleased to present to our readers the proceedings of the Fourth Bari Seminars in Nephrology. The Topic of these proceedings deals with tubulo- interstitial nephropathies. The Bari Seminars in nephrology are bi-annual meetings attended by a large international audience comprised of clinician-scientists in the various disci- plines of nephrology and related fields. We trust that our readers will find the content of these proceedings reward- ing and interesting. We are indebted for the generous financial support of the Centro Nationale delle Richerche, Italy. Alberto Amerio Pasquale Coratelli Shaul G. Massry TUBULO-INTERSTITIAL NEPHROPATHIES 1 STRUCTURAL, ASPECTS OF THE RENAL INTERSTITIUM W.KRIZ AND K.V. LEMLEY Institute of Anatomy and Cell Biology, University of Heidelberg, D-6900 Heidelberg 1, F.R.G. Childrens Hospital of Los Angeles, Division of Nephrology, Los Angeles, U.S.A. The interstitium of the kidney includes the extravascular inter- tubular spaces of" the renal parenchyma, with their attendant cellular elements and extracellular substances. It is bounded on all sides by tubular and vascular basement membranes. The lymphatics are considered as part of the interstitium.

Many groups of biologically important compounds experience cycles of furious research activity and near oblivion. The purines however seem not to be falling into such a pattern. Interest seems to be continuing almost exponentially with no sign of diminution. The result is a frighteningly extensive literature and an increas ing demand for international conferences and symposia. Unfortunately meetings such as these also spawn increasingly voluminous proceedings and it becomes more and more difficult for a newcomer to the area, or a non specialist, to obtain the general introductory survey he needs. This volume therefore is not intended to be comprehensive - far from it. We have tried to be selective in the material presented and the references quoted. They should provide a quick guide and access to key works in the literature which can be expanded by library or computerised searching. We hope that our efforts will widen the appreciation of purines as biologically important substances and will herald the day when more purine related drugs than the handful currently available are used for the selective treatment of disease. We are grateful to the many authors and publishers who have given permission to reproduce figures or quote unpublished results, and to Anne Stone for her patient typing of the manuscript."

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.

We are pleased to present to our readers the proceedings of th~ Third Bari Seminars in Nephrology. The tDpic ~f these proceedi~gs deals with effects of drugs and o:.yst el'll C ct i se;'Isc;- an the Id dney. Tho B?rj S~~jnar5 in Nephr~logy are bi-annual meetings ~tt~~~Dd k) D large international audience comprised of clinicians-scientist~ in the various displines of ~~phrnlDgy nnrl rQlated fi~ld$. The ne~t Bari S~mjnar5 of Nephrology will take place i" npril 19qn ~nd thp theme of the gathering will be Interstitial Nephritidies and Obstructive Uropathy. We are indc-bted for the goner-ells financial support of the Centro N::I~innalC' tiGBP:'llGBP'", Pichp.rche, Italy. Alberto Amerio Pasquale Coratelli Vito M. Campese Shaul G. Massry vii CONTENTS Lupus Nephritis: Pathogenesis, Course and Management .*..*...3 James E. Balow Prognostic Determinants in Lupus Nephritis ...*...* 17 P. Coratelli, R. Rizzi, G. Pannarale, A. Ramunni M. Giannattasio, and G. Passavanti Thrombotic Microangiopathy in Lupus Nephritis . * * . . 35 . M.T. Porri, M.I. Quarenghi, F. Ferrario G. Colasanti, R. Rossi, E. Schiaffino, G. Toia, and G. D'Amico Vasculitis and the Kidney . * ...* ...* * * 41 .

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.

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.

Major advances in both the technology and the medical knowledge of maintenance hemodialysis have been made since the early stages of such treatment in the 60s. Hemodialysis is now an established therapeutic method. and the time has come to present an up-to-date approach to all its technical and medical aspects. We adopted a simple and concise style with a clear design and a large number of tables and illustrations. so that not only health professionals but patients themselves can easily understand the essentials of hemodialysis. In addition to the most recent technical developments of hemodialysis. particular attention is given to biocompatibility. adequacy of dialysis and patient nutrition. The many clinical problems encountered in the dialysis patient have been especially emphasized. since proper management may prevent most uremia-related complications. Indeed. chronic hemodialysis consists not only of providing the patient with safe and well-tolerated dialysis sessions but also of maintaining good general condition, adequate nutritional status and well-being in the long term. All of us have worked in the field of nephrology and hemodialysis at Necker Hospital for more than 25 years, and several of our very first patients are still enjoying life thanks to hemodialysis. We hope that our experience will be of help to nephrologists. renal nurses and technicians in training so that they can offer their patients, through optimal dialysis, long survival with the best possible quality of life and rehabilitation.

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."

Cardiac disease is the major cause of death in dialysis patients, accounting for over one third of deaths. This book focuses on myocardial function and dysfunction in chronic uremia. It is aimed at practicing and training nephrologists, cardiologists, and internists, and at research workers in the field. We have tried to produce an up-to-date, in-depth review of the subject by inviting experts in clinical epidemiology, pathophysiology, and thera peutics to write the 18 chapters. The book is divided into three sections. The first section comprises five chapters that provide an overview of the burden of illness associated with cardiac disease in end-stage renal disease and a review of clinical epidemi ological aspects of various cardiac diseases that occur in renal patients. The second section discusses abnormalities of left ventricular contractility and mass, and the factors that predispose to both systolic and diastolic disorders. The importance of hypertension, anemia, hyperparathyroidism, hyper lipidemia, and diabetes mellitus in predisposing to these abnormalities is reviewed splendidly by researchers active in these areas. The final section concentrates on therapeutics. Data and opinion on management of congestive heart failure, cardiomyopathy, coronary artery disease, hypertension, and arrhythmias are provided. In editing this book, we have reviewed an extensive literature, but un fortunately we have become more aware that substantial gaps in our knowl edge exist. Insufficient high-quality clinical research has been undertaken xiii xiv Preface regarding the various cardiac diseases that occur in end-stage renal disease."

Drug dosage in renal insufficiency has become an toxication. In 1975, his Poison Index was pub important facet of nephrology, a subspeciality of lished, first in German, and two years later in internal medicine which is only 30 years young but English, with supplements in 1979 and 1983. This constantly growing in scope and importance. Two volume has become an obligatory reference in more thirds of all drugs are partially, mainly, or exclu than 2500 dialysis units. sively excreted by the kidneys. In the presence of Based on GOnter Seyffart's experience and renal insufficiency, dose adjustments are therefore knowledge in this field, the plans for this book obligatory. In patients on dialysis, drug elimination matured in 1984, a logical step in view of his by this route must also be considered. untiring effort and diligence. In order to deal with As the reader of this book will discover, 20 more than 1200 different drugs and almost 4000 percent of currently used drugs are contraindicated references, 21 contributors were sollicited, while it where there is any degree of renal insufficiency, took six years to complete the work. The major and for at least another 60 percent a dose reduc share of the effort was thus left to the main author tion is required. It is obvious, therefore, that the and editor and he has produced a concise work of detailed knowledge required can never be com impressive clarity.

Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.

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.