This text covers the basic principles of mitochondrial dynamics in cardiovascular medicine, with particular emphasis on their functional roles in physiology and disease. The book will include articles pertaining to mitochondrial fitness on a global basis, providing therefore an update on the progress made in several aspects in the field. Thus, it will assist scientists and clinicians alike in furthering basic and translational research. Organized in sections focusing on: basic science, mitochondrial dysfunction in cardiac disorders, in vascular disorders, in metabolic disorders, in kidney disease, therapeutic challenges and options, this essential volume fills imperative gaps in understanding and potentially treating several cardiovascular disorders.

This comprehensive volume provides a detailed review on the general work up of chronic kidney disease-associated resistant hypertension. This title is separated into four parts; the first of which provides definitions, epidemiology, characteristics, risk stratification and outcomes of resistant and apparent treatment resistant hypertension. The next two sections explore pathophysiology and diagnosis, treatment in the light of new guidelines, as well as procedures and devices for neural modulation. Part four discusses public health approaches to resistant hypertension, educational programs, and resistant hypertension for general practitioners. Resistant Hypertension in CKD brings up-to-date information to nephrologists, internists, cardiologists and a wide array of other clinicians and health professionals taking care of chronic kidney disease patients.

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.

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."

This volume provides an in-depth review of the data relating to the management of renal tumors as well as an updated description regarding pathologic and molecular classification of renal tumors. The neoplasms covered include clear cell carcinomas, papillary cancers, nonepithelial tumors, and other mass lesions that resemble tumors. The management of patients with renal cancer having localized or advanced disease is discussed. Surgical approaches for primary and metastatic tumors, symptom palliation, and systemic therapy for metastatic disease including immunotherapy and targeted approaches are discussed in detail.

Cardiovascular complications are not only responsible for more than half of our patients' mortality, they also represent the bulk of everyday problems in a dialysis unit. Yet, the space allocated to them in the major textbooks covers only 2-8% of their total content. The origins of this book lie in many years of day-to-day care of dialysis patients. It gradually became clear to the author that systematic application of well-known pathophysiological principles could improve patients' conditions beyond expectations. More importantly, it appeared that world literature was mainly concerned with evaluating risk factors and that efforts to improve prognosis were concentrated on urea removal. It is important, therefore, to notice that Volume Control', the central issue of this book, is not incorporated into the Adequacy' concept. While primarily intended for dialysis doctors, the author sincerely hopes that dialysis nurses, who carry the lion's share of day-to-day responsibility for dialysis patients, will also find this book a useful and practical guide to dialysis treatment.

Genetic disorders have emerged as a prominent cause of morbidity and mor tality among infants and adults. As many as 10% to 20% of hospital admis sions and at least 10% of the mortality in this age group are due to inherited diseases. There are at least two factors that have brought genetic disorders into the forefront of pediatrics. One is a great reduction in childhood mortality due to infections and nutritional deficiency states, and the other is the rapid progress made in the identification of genetic defects. Amniocentesis, chorionic villus sampling, and recombinant DNA technology have already had a tremendous impact on the practice of medicine. This is why the first two chapters of this volume are dedicated to general principles of molecular genetics and to a description of the techniques used to diagnose genetic disorders at the DNA level. The relevance of this new area of science to the study of inherited renal diseases is reflected in the large body of knowledge that has been generated regarding the association between various glomerular nephritides and genetic markers such as the HLA system, and even more impressively in the direct or indirect identification of abnormal genes or gene products in Alport's syn drome, autosomal dominant polycystic kidney disease, and Lowe's syndrome. These discoveries figure prominently in the pages of this book. Yet, the progress we have made has barely scratched the surface of the problem."

The initial observations of dialytic support were brought from the laboratory and confined to patients with reversible acute renal failure. The thought at that time was one of short term maintenance. It was theorized that removal of waste products from the blood, albeit incomplete and inefficient, might allow these patients time to regenerate damaged tubules and regain renal function. After a dis appointing earlier experience in survival, greater sophisti cation and broader practice refined the dialysis skills and reduced mortality. It also became apparent that long periods of support were possible and successful attempts were then made in utilizing this technology in patients with chronic renal failure. These early young patients were a very select group who possessed only renal dysfunction and no other systemic involvement. Nonetheless, they demonstrated a one year survival of only 55-64%. There are presently over 80,000 patients on dialytic support in the United States and over 250,000 patients worldwide dependent on artificial replace ment. Mortality statistics vary but despite a 20-30% systemic disease involvement and a fifth decade average age in the North American experience, the one year survival has risen to apparently 90%."

Enormous progress has been made in the treatment of chronic renal failure over the last decades. Until the 1950s, chronic renal failure was considered to be an inexorably lethal condition. This is no longer the case. In addition, the disease, severe uremic syndrome, is now extremely rare, if existent at all, in industrialized countries. Physicians of my generation who saw patients hospitalized with hemor raghes, pericarditis, severe anemia, cardiac failure, "malignant hypertension," pruritus, vomiting, generalized edema, and convulsions are particularly grate ful for this progress. I well remember seeing such patients hospitalized in the last days or weeks of their lives and also remember the sense of impotence I suffered for the com plete lack of efficient measures I had at my disposal to manage their condition. Nowadays, hemodialysis, peritoneal dialysis, and kidney transplantation allow patients with chronic renal failure to survive for very long periods of time in a satisfactory condition. Why then is there still a sense of dissatisfaction and why should we study dietary management? The drawbacks of dialysis and transplantation are the main reasons, but the certainty that dietary therapy is complementary to dialysis and even better than dialysis in certain conditions, is also very important."

Seeing a patient die under his hands because there is no adequate treatment causes an emotion and a frustration in a doctor, which sometimes stimulates him to try to develop a new type of treatment. Seeing so many wounded young soldiers die due to renal failure in World War I incited the German doctor Georg Haas to try to develop an artificial kidney. He had to give up in despair in 1928. Ten years later doctor Willem Kolff saw a young man die in his ward in the University Hospital of Groningen due to renal failure. By that time two essential factors for an artificial kidney had become available: a drug to keep the blood from clotting outside of the body and an efficient dialysing membrane through which waste substances can pass from the blood into the dialysing fluid. Kolff succeeded in creating the rotating artificial kidney which he started using in the town hospital of Kampen in 1943. The rotation of this artificial kidney started a revolution that made it possible for thousands of kidney patients all over the world to keep on living - and sometimes to forget their disease for the time being. In addition it gave rise to the development of other artificial organs such as the heart-lung machine, the artificial heart and the artificial eye. Doctor Jacob van Noordwijk, the author of this book, was Kolff's first assistant in the treatment of the first 15 patients. How Kolff succeeded in spite of all the limitations imposed by the German occupation of the Netherlands and in spite of the absence of antibiotics and other medical tools which are common nowadays makes a story which may sound incredible. Yet it did happen and visitors to the town of Kampen can still see the hospital building where it all took place.

Kidney cancer is a heterogenous disease. This book covers:

-new surgical approaches which are becoming the standard, i.e., nephon sparing, laporascopic, minimally invasive techniques;
-new staging and prognostic capabilities;
-evolving therapeutic options include, cell based vaccine, gene and antibody therapy;
-molecular genetics allow for a better understanding of the various types of kidney cancer. Kidney Cancer is a comprehensive review covering present and future surgical approaches, staging and prognostic factors, currently accepted and future plans for prevention, diagnosis and treatment. Contributing authors to this book are internationally recognized specialists in this disease. This book will be useful to the specialist (oncologist and urologist), primary care physicians, patients and family members dealing with kidney cancer.

CHARLES Y. c. PAK Major progress has been made in the pathophysiologic elucidation and management of nephrolithiasis during the past two decades. It is now possible to detect the cause of stone disease in more than 95% of patients, to prevent recurrent formation of stones in the majority of patients, and to remove most existing stones less invasively. The assumption of editorship of this book permits me to indulge in the discussion of this progress from my personal perspective. Three somewhat fortuitous events in my academic career dictated my directing major efforts in stone research. The first event occurred in 1963 when, after having completed medical training, I was faced with two years of military service as a participant of the Berry plan. Choices were limited and disconcerting for someone interested in a research career: a staff physician at a military installation or an indian reservation, or a member of a research team in a state penitentiary. An interesting article by Norman Gershfeld on phospholi pid monolayers prompted me to write him seeking a position in his laboratory of Health (NIH) in Bethesda, MD. Partly because of at the National Institutes my rudimentary exposure and publication in surface chemistry, I was offered a position as a staff scientist and a position in the Public Health Service which satisfied the requirements of a military service."

"Where are all these kidney patients coming from? A few perfection the study of the urinary sediment, clinically years ago we had never heard of kidney disease and now practical kidney function tests, and the natural history of a number of kidney diseases including glomerulonephritis. you are speaking of patients in the hundreds of thousands and indeed potentially millions. " My reply, not meant to William Goldring, Herbert Chasis, Dana Atchley, and others studied the effects of hypertension, endocarditis, be grim, was "From the cemetery, Sir. " This is a summary and circulatory diseases on the kidney and spawned suc of some Congressional testimony lance gave on behalf of extending kidney disease under Medicare. Where indeed cessive generations of alert clinical investigators, who be gan to chronicle the natural histories of a wide variety of were all the patients with kidney disease in the United States before World War II? They were certainly not kidney diseases. Quantitative studies of renal function flourished under a school headed by Homer Smith, and under the care of nephrologists! Nephrology was not listed in the questionnaires for any state or the American Medi surprisingly precise techniques were developed for study ing a whole range of explicit nephron functions. Imagine cal Association as a subspecialty or even as a special the joy with the advent of vascular catheterization to be interest.

Rodney Appell, and a host of respected clinical experts comprehensively summarize the state-of-the-art in the diagnosis and treatment of both neurogenic and nonneurogenic urinary problems in males and females alike. Tailored for use by today's busy practicing urologists, as well as frontline physicians, this book provides the essential physiological background for classifying voiding dysfunctions, surveys the practical diagnostics for these dysfunctions, and reviews the available treatments, including pharmacologic therapy, electrical stimulation, and surgery. Informative, practical, and clinically relevant, Voiding Dysfunction: Diagnosis and Treatment brings to every physician's treatment room a first-class compendium of the latest scientific facts, the best methods of diagnosis, and the most appropriate and effective treatments for these disturbingly widespread disorders.

The year was 1943. As a third-year medical student at Stanford, I was about to witness the beginning of a medical miracle. Dr. Arthur Bloomfield, Professor of Medicine, had selected my patient, a middle aged man, who was dying of acute pneumococcal pneumonia, as one of the first patients to receive miniscule doses (by today's standards) of his meagre supply of a new drug - penicillin. The patient's response amazed everyone especially this impressionable medical student. The rest of the story is history. With one stroke, the introduction of penicillin removed from the medical scene the 'friend of the aged' - lobar pneumonia. The consequences, which no one could have imagined at the time, are still becoming manifest as other 'miracles' such as respirators, artificial kidneys and many potent new antibiotics have come upon the scene. All of us are aware that these miracles have created a variety of new challenges around the states of dying and near dying. We have no easy answers for these problems. Nevertheless as dialysis techniques, especially CAPD, are applied more widely to the treatment of the elderly, the task of helping the patient meet death with dignity becomes increasingly important and vexing because once begun, dialysis is difficult to terminate.

Major nephrological and psychological organizations have, at best, set aside only small portions of their programs for papers or panels devoted to the psychological aspect of patients with end-stage renal disease. Thus, the increased need for information concerning the psychological aspects of end-stage renal disease has been met by occasional journal articles, professional peer discussions, small portions of national confer ences, and informal conversations and consultations with people with clinical and research experience in these areas. The First International Conference on Psychological Factors in Hemodialysis and Transplantation arose out of a need to have a forum in which the major people involved in treatment and research in this area could share their latest work among themselves and with the registrants. The initial encouragement for organizing such a conference came from the rank and file of nephrology social workers, nephrology nurses, and liaison psychiatrists and psychologists. In early 1977 I had decided that I would make an effort to organize such a meeting and asked the two other individuals most closely identified with major research in this area, Atara Kaplan De-Nour and Harry S. Abram, to join me in planning this confer ence. With their support and suggestions concerning the program, I embarked upon an attempt to raise financial backing for it. I was some what surprised to find that the many equipment and drug companies supporting nephrological conferences were not greatly interested in this one."

Renal stone disease remains a common clinical problem. Patients m a y attend either medical or surgical clinics and n o t infrequently present as acute abdominal emergencies to general practitioners, physicians, surgeons and even gynaecologists. Recent urinary calculi continue to cause considerable morbidity despite the recent advances in our understanding of the pathogenesis of the different types of stones involved and despite improvements in t reatment- by appropriate drug therapy, by ultrasound techniques and by lithotripsy. This volume discusses the investigation and management o f patients with calculus disease. Each chapterhas been written by a n experienced clinician and provides information of considerable relevance and importance for all doctors engaged in clinical practice. The technical developments o f the last few years have clearly demonstrated that renal stone disease, even when recurrent, should be an uncommon cause of chronic renal failure. Knowledge o f the recent developments in this field is important for all practising doctors and even more important for their patients.

Proceedings of the FEMS Symposium on Genes and Proteins Underlying Microbial Urinary Tract Virulence: Basic Aspects and Applications, held September 16-19, 1999, in Pecs, Hungary. Urinary tract infections are among the most frequent diseases caused by microbial pathogens. In this volume, researchers, clinical microbiologists and clinicians exchange the latest ideas covering four major aspects of this important topic: Genetic information, synthesis and assembly of virulence factors in urinary pathogens; Regulation of genes involved in the phenotypic appearance of virulence; Host-parasite interactions determining the process and outcome of the infection; Possible applications of the above aspects in diagnosis, therapy and prevention. "

In 1986, the Committee of Experts on Blood Transfusion and Immunohae- tology of the Council of Europe chose for their Programme of Co-ordinated Research "An investigation of the procurement and sharing of transplantable organs for potential recipients who are highly sensitized to HLA-antigens." This topic was of common concern to all centres practising renal transplan- tion. The terms of reference of the study were: To estimate the number of patients who are virtually "untransplantable" because of high sensitization in each European country. To study the nature of immunization in terms of the type and specificity of antibodies present in the blood and techniques used for their detection. To investigate possible practical solutions - both current and future, invo- ing cross-matching procedures, the circulation of reference material from patients, and the willingness of the national organizations to share resources. 4. To explore other methods of resolving this problem. Although the study did not offer the prospect of a brilliant new insight into the problem of high sensitization, it was unique in several ways: for the first time we saw all European organizations collaborating in a common project to provide information on their activities, their problems and the methods to resolve them; it introduced, for this subject, relatively novel statistical methods to investigate susceptibility to sensitization and factors affecting transplant outcome; it enabled a large database of transplanted highly sensitized patients and matched controls to be assembled, that would have been unavailable as a research resource at any single centre.

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."

The purpose of this volume and Pediatric Nephrology Seminar IX from which it was created is to provide easy access to current concepts in the diagnosis and management of kidney diseases in the newborn. Complimentary to this purpose is the opportunity the Seminar structure gives me to invite those particularly interested in the subject chosen to come together, share experiences and ideas in an unhurried, unpressured atmosphere for four con tinuous days - an oasis for me and, I am told, also for the faculty and registrants. This year's subject choice is an expression of my perennial interest in the kidney of the newborn. A step back to view the steps forward reveals unwittingly intertwined associations and actions which now fall into focus. When I was just beginning my pediatric nephrology training with Sol Kaplan at Downstate in Brooklyn, we discussed Bob Usher's pioneering thought that there was something wrong with the kidneys of babies with RDS. Without really knowing what needed to be done, I started looking at the kidneys of those babies. Subsequently, Dick Day who was Chairman of the Department of Pedia trics there, stopped me in the hall, and asked me to come into his office. Glowing in quiet introspection, he extolled the joy of working with one's hands, then hurried away to his laboratory. He had been the Director of the Newborn Nursery at Babies Hospital before coming to Downstate, and (as I later found out) was trying to do something with oxygen electrodes."

Hepatic Encephalopathy (HE) is a neuropsychiatric disorder resul t- ing from liver failure. HE may be associated with fulminant (acute) hepatic failure or chronic liver disease with portal-systemic shunting. The latter condition is characterized neuropathologically by astro- cytic rather than neuronal changes (Alzheimer Type II astrocytosis). The former is frequently accompanied by cerebral edema. Several hypotheses have been proposed to explain the pathogene- sis of HE. These include: 1. A toxic action of a substance (or substances) such as ammonia on brain function 2. A deficit of cerebral energy metabolism 3. Neurotransmitter changes, and, more recently 4. The role of "endogenous benzodiazepines. " This volume summarizes the results of a symposium held in Val David, Quebec from October 3D-November I, 1988, that was devoted to an evaluation of the evidence for and against the various hypothe- ses of HE. Data from studies in patients, in experimental (animal) models of HE, and in cultured cell preparations were discussed. In addition, a review of available approaches to the treatment and man- agement of HE was included. The therapeutic use of lactulose, anti- biotics, dietary treatment, and branched-chain amino acid treatments were included, as well as the results of preliminary studies of the therapeutic use of the benzodiazepine antagonist, flumazenil. Roger F. Butterworth, PhD Gilles Pomier Layrargues, MD v Acknowledgments The symposium was made possible by the generous financial assistance of: Hoffman-La Roche Ltd.