The need for adequate means by which to improve urine output is very old. Even in the "Scuola Salernitana", the oldest medieval medical school in Western Europe, about 1000 years ago it was taught how to improve urine output. The list of known "diuretica" included herbs, plants, roots, vegetables, in particular asparagus, fennel and carrot. The first diuretic drugs, however, were mercurial compounds. Thus, calomel, mercurous chloride, was initially used as a diuretic in the sixteenth century by Paracelsus, being one of the ingredients of the so-called "Guy's Hospital pill". But calomel had a cathartic effect so that it was replaced by organic mercurial compounds. These diuretics were clearly toxic. After the discovery of the car bonic anhydrase, in the early 1930s, and the introduction of sulfanilamide as a chemotherapeutic agent, it was observed that this drug was inhibiting carbonic anhydrase in vitro and urinary acidification in vivo thereby causing metabolic acidosis; urine output, however, appeared to increase. Subsequent studies led to the synthesis of more potent analogs, in particular acetazolamide. Studies on car bonic anhydrase inhibitors led to the synthesis of benzothiadiazides which disclosed much less inactivating action on carbonic anhydrase and much more diuretic effect through an inhibition of tubular transport of sodium and chloride. Chlorothiazide was the first member of this class of diuretics. Thiazides are still used in clinical practice.

Anti-native DNA antibodies and DNA are present in cryopreClpItates from patients with systemic lupus erythematosus and some other cryoglob ulinemic states. The data suggest that these antibodies may be bound in immune complexes. The demonstration of native DNA in these precipitates raises the likelihood that they represent specific antigen in these complexes. Whether or not these complexes play a pathogenetic role in nonlupus inflammatory diseases remains to be demonstrated. References Aarden, L. A., de Groot, E. R., and Feltkamp, T. E. W., 1975, Immunology of DNA. III. Crithidia luciliae, a simple substrate for the determination of anti-dsDNA with the immu nofluorescence technique, Ann. N.Y. A cad. Sci. 254:505. Agnello, V., Winchester, R. J. and Kunkel, H. G., 1970, Precipitin reactions of the Clq component of complement with aggregated 'Y-globulin and immune complexes in gel diffusion, Immunology 19:909. Anker, P., Stroun, M., and Maurice, P. A., 1975, Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system, Cancer Res. 35:2375. Bankhurst, A. D., and Williams, R. C., 1975, Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus, ]. Clin. Invest. 56:1378. Bluestone, R., Goldberg, L. S., Cracchiolo, A., and Barrett, E. V., 1970, Detection and characterization of DNA in mixed (IgG-IgM) cryoglobulins, Int. Arch. Allergy Appl. Immunol. 39:16."

The first edition of this book was well received by updated. The two of us have made further collab orative efforts to present a better understanding of medical students, graduate students, and clinicians interested in furthering their understanding of basic the function of the kidney in conjunction with the principles of renal physiology. Most of the reviews most recent anatomical findings. of the first edition and comments from the various The second edition consists of 13 Chapters and 3 instructors who used the book were very positive Appendices. As in the first edition, the anatomical and complimentary with regard to the presentation description of the kidney is incorporated into the of the physiological information and the use of the various chapters dealing with kidney functions. Most system analysis approach to describe renal function. of the anatomical information was written by Wil These positive and encouraging comments over the helm Kriz. The physiological information was writ past nine years, since the publication of the first ten by Esmail Koushanpour, except for Chapter 12 edition, gave us the impetus to consider the prepa which was jointly written. Chapters 1 through 3 were ration of a second edition."

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of on cology."

The last 20 years has seen an enormous increase in our knowledge about the management of patients with terminal renal failure. Despite this, even the most successful dialysis and transplant patients require long term specialist supervision so that renal units will have an incremental work load until the death rate of patients undergoing treatment equals the rate of intake of new patients. Furthermore, innumerable conditions which were once regarded as contraindications to therapy may no longer be seen in this light, so that the number of new patients coming forward for treatment each year is increasing rapidly. Dialysis and transplantation are expensive forms of treatment, in terms of staff, facilities and consumables, and it is therefore inevitable that there will be problems in providing treatment for all who need it. These will be particularly acute in times of economic crisis. This book contains the proceedings of a conference which was set up to explore the difference between the supply and the demand for treatment in the United Kingdom, to compare the situation with that in other countries, to explore possible solutions and possibly assign responsibility for the shortfall and to examine the practical and moral implications of our failure to treat the treatable.

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

This book contains 55 chapters that summarize referred to the special issue of Drug Development lectures given during the Fifth International Research (Volume 31, Number 4, April 1994). Symposium on Adenosine and Adenine Measured by the number and quality of presenta- Nucleotides held in Philadelphia, Pennsylvania, tions, and by the record number of participants, U. S. A. , May 9-13, 1994. The symposium and the Fifth International Symposium on Adenosine its proceedings follow four previous symposia and Adenine Nucleotides was clearly an intel- and their published proceedings. Previous sym- lectually stimulating meeting. It is safe to posia were held in Banfff, Canada (1978), conclude that the purine research field is vibrant Charlottesville, Virginia (1982), Munich, and still growing. Adenosine has rapidly become Germany (1986), and Lake Yamanaka, Japan the drug of choice for the acute management (1990). of supraventricular tachyarrhythmias and was The program included a wide range of sub- recently approved for use in combination with jects from molecular and cellular biology to cardiac imaging for detection of ischemic heart clinical applications. Great emphasis was placed disease. Additional clinical applications of on cutting edge information derived from studies adenosine and adenosine-related drugs and ATP using molecular and cellular biology techniques seem closer than ever before. The editors would like to express their grati- applied to the field of adenosine and adenine nucleotide research. Likewise, the program tude to the distinguished contributors for their included a number of presentations on poten- excellent chapters and to all participants.

Once dialysis treatment, in 1960, permitted life prolongation for some but not all patients in kidney failure, an ethical genie' was released. The introduction of peritoneal dialysis and kidney transplantation compounded the physician's dilemma by underscoring those left untreated. Who should be selected for uremia therapy? Should exclusion from treatment be properly delegated to administrators or physicians, or better left to a committee? Are some candidates more worthy than others? As examples: Do Presidents and Kings warrant priority in cadaver organ allocation over ordinary citizens? Are rich people more deserving than the poor? Is it ethical to choose a younger over an older patient? Can children and/or mentally incompetent persons serve as living organ donors? Is it proper to market organs under controlled circumstances? Eli A. Friedman, an experienced nephrology training program director, and Medical Advisor to the American Association of Kidney Patients, has collected 24 difficult cases that focus on these and other vexing though common stressful issues faced by those who manage kidney patients. Using a novel approach to each case, the opinions of lawyers, nephrologists, patients, and a transplant surgeon are proffered sequentially. Friedman asks and then answers searching questions arising from the debate. The quality of information presented is positively flavored by the fact that three of the respondents (one an attorney) are kidney transplant recipients. Members of the kidney team, those immersed in seeking truth in medical ethics, and all participating in exploring the legality or ethical basis of organ replacement will find this book pertinent to their effort.

Fresh insights into the pathogenic mechanisms by which hyperglycemia induces tissue and organ injurt are the basis for rapidly evolving promising therapies in diabetes. Especially promising as targets for intervention are products of oxidative stress, including kinins and growth factors. Improving results of renal replacement regimes now incorporating pancreatic islet transplants are able to delay and prevent end-organ damage in diabetic individuals. The evolving story of the taming of diabetes is of direct concern to nephrologists, endocrinologists, ophthalmologists, primary care physicians and medical students.

Since oxygen is mainly transported by diffusion within tissue, the oxygen pressure field reflects the local balance between oxygen supply and oxygen consumption and characterizes the state of oxygen supply. Despite large physiological varia- tions (e. g. , hypo-and hyperoxia, hypo-and hypertension, change of energy de- mand), this oxygen pressure field can remain remarkably constant, demonstrating that very effective mechanisms must exist that guarantee the adequacy of oxygen supply. Today, it is possible to describe in detail the responsible effector mecha- nisms that produce such a stable state of oxygen supply, but our knowledge of the reactions that sense tissue oxygen supply and trigger the regulatory responses is still incomplete. Since such knowledge is essential for understanding the system of oxygen supply and the way in which it has developed during evolution, even small progress is important. In this book the important O sensor reactions are discussed as they occur in 2 cells, organs, and organ systems. This broad approach gives an excellent picture of the actual state of knowledge in this field. Professor Dr. D. W. Lubbers Contributors Acker, H. Max-Planck-Institut fUr Systemphysiologie, Rheinlanddamm 201, 4600 Dortmund 1, FRG Bassenge, E. Institut fUr Angewandte Physiologie der Universitat Freiburg, Hermann-Herder-Stral3e 7, 7800 Freiburg, FRG Bingmann, D. Poliklinik fUr zahnarztliche Chirurgie, Universitat Mainz, Augustusplatz 2, 6500 Mainz, FRG Bauer, C. Physiologisches Institut, Universitat Zurich, Winterthurerstral3e 190, 8057 Zurich, Switzerland Busse, R. Institut fUr Angewandte Physiologie, Universitat Freiburg, Hermann-Herder-Stral3e 7, 7800 Freiburg, FRG Delpiano, M. A.

I am honored to be invited to prepare a foreword for the proceedings of the Second International Lubeck Conference on Erythropoietin (Epo). I congratulate Wolfgang Jelkmann, Horst Pagel and Christoph Weiss for their organization of an excellent program for this conference which updated all of us on the advances made in erythropoietin research during the past few years since the first conference in June of 1988. I am sure that Professor Paul Carnot, had he been present at this conference, would be very pleased and proud of the advances made in the field of erythropoietin since his and Madame DeFlandre's seminal finding in 1906 (1) that rabbits produced a humoral substance following bleeding which controls red blood cell production. The reports by Hjort in 1936 (2) and by Erslev in 1953 (3) that large volumes of plasma or serum from rabbits following a bleeding stimulus, when injected into normal donor rabbits, produced a reticulocytosis, were very significant in confirming the existence of a humoral factor which controls erythropoiesis. Reissmann's parabiotic rat experiments in 1950 (4) reawakened interest in erythropoietin when he proved that hypoxia stimulated the production of a factor which regulates red cell produc tion. The studies of several investigators such as Jacobson et al. (5), Fisher and Birdwell (6), Kuratowska et al. (7) and Nathan et al."

The aim of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY is to publish every year a volume to keep nephrologists up to date on all the rapidly changing areas of nephrology. Each volume will be published by the end of each calendar year which corresponds with the annual meeting of the American Society of Nephrology. Each issue of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY will be divided into sections; each section will have different primary focus every year, depending upon what area is of greatest interest at the time. In other words, each annual volume will deal with what is truly current in nephrology. All the authors appointed for the chapters of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY are known experts in the field who will give an objective review of the topic up-dating the readers on the world-wide literature. A crucial point for the success of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY is the list of the references at the end of each chapter. We have asked all authors to provide a complete, accurate and up-to-date list of important references. In order to guarantee the most up-to-date yearbook, very rapid production is mandatory. Rapid publication can be obtained only with camera-ready manuscripts for direct photo-offset reproduction. Thus we have agreed to use photo-offset printing for the series. For the first issue of the series, the INTERNATIONAL YEARBOOK OF NEPHROLOGY 1989, the Editorial Board has focused attention on the latest and most important scientific and clinical advances in nephrology.

Urinary tract infection remains one of the most common reasons for an individual seeking medical advice. Although the associated morbidity varies widely in adults, such infections are less common but may constitute severe, life-threatening illness in children and in the elderly. Diagnostic tests and treatment have been rationalized in recent years but many practising doctors still have difficulty in appreciating the patho-physiological principles involved. Particular difficulty is often experienced when treating patients with recurrent urinary tract infections, covert bacteriuria, vesico-ureteric reflux, elderly patients and those with indwelling catheters. These topics are fully discussed in this volume. Each chapter has been written by a recognized expert and practical aspects of patient management have been emphasized. The information presented in this volume should prove of interest not only to nephrologists but to all practising clinicians. VII ABOUT THE EDITOR Professor Graeme R. D. Catto is Professor in Medicine and Thera peutics at the University of Aberdeen and Honorary Consultant Phy sician/Nephrologist to the Grampian Health Board. His current interest in transplant immunology was stimulated as a Harkness Fellow at Harvard Medical School and the Peter Bent Brighton Hos pital, Boston, USA. He is a member of many medical societies includ ing the Association of Physicians of Great Britain and Ireland, the Renal Association and the Transplantation Society. He has published widely on transplant and reproductive immunology, calcium metab olism and general nephrology."

For more than a generation haemodialysis has been the principal method of treating patients with both acute and chronic renal failure. Initially, developments and improvements in the system were highly technical and relevant to only a relatively small number of specialists in nephrology. More recently, as advances in therapy have dem onstrated the value of haemoperfusion for certain types of poisoning, the basic principles ofhaemodialysis have been perceived as important in many areas of clinical practice. In this volume, the potential advantages of bicarbonate haemo dialysis are objectively assessed, the technical and clinical aspects of both haemofiltration and haemoperfusion discussed and the con tinuing problems associated with such extracorporeal circuits analysed. All the chapters have been written by recognized experts in their field. The increasing availability of highly technical facilities for appropriately selected patients should ensure that the information contained in the book is relevant not only to nephrologists but to all practising clinicians."

For more than a century, the condition now known as Idiopathic Hydronephrosis has been recognised as a clinical entity, and following the original description by Rayer in 1841 a variety of procedures were devised in attempts to correct the condition surgically. Most of these early methods were introduced in the last decade of the nineteenth century by several illustrious clinicians, including Trendelenburg, KOster, Fenger and Sutton. For many years diagnosis was based purely upon the patients presenting signs and symptoms and not until the early part of this century was technology available to assist in the pre-operative diagnosis of the condition. Early methods depended upon radiological techniques, and the introduction of the retrograde pyelogram by Voelcker and Lichtenberg in 1906 represented a significant advance in diagnostic methodology. Other methods also dependent upon radiographic techniques were subsequently introduced, including urography in the late 1930s by Swick, and more recently, the method of cineradio graphy, as pioneered with considerable success by Peter Narath in the decade following World War II. During the past 50 years a variety of surgical procedures have been introduced for the treatment of idiopathic hydronephrosis. That so many different methods have been devised suggests that no one specific technique is capable of achieving a complete cure in all cases."

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

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

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

Combining principles of contemporary immunology with applications to immunopathology, this up-to-date volume documents new developments in the understanding of the origin of autoimmune diseases. Emphasized are cellular and molecular approaches in both organ-specific and systemic autoimmunity. A comprehensive bibliography, numerous illustrations, and tables make it an invaluable source of information for immunologists, rheumatologists, pathologists, dermatologists, and nephrologists.

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

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

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

The mechanisms by which animals regulate the volume and composition of their body fluids has long had a particular fascination for students of biology. As a consequence, the subject can lay claim to an impressive record of ground breaking scientific achievements as well as a provocative body of philosophical speculation concerning the role of the system in the origin and evolution of life. Indeed, the entire concept of homeostasis on which so much of o r current biologic thinking is based, derives from Claude Bernard's pioneering exploration of the forces that determine the composition of this 'internal sea'. Other seminal achievements credited to this area of inquiry include the first description of a genetically transmitted human disease (familial neurogenic diabetes insipidus); the first isolation sequencing and synthesis of a peptide hormone (vasopressin and oxytocin); the first demonstration of peptide hormone synthesis by way of a larger protein precursor; the first description of resistance to the biologic actions of a hormone (nephrogenic diabetes insipidus); and the conceptual realization of the unique counter-current mechanism that permits concentration of the urine. This record of far reaching and fundamental advances has been distinguished by many fruitful inter actions between clinical and basic science."