Biologics have revolutionised the treatment of many severe conditions, delivering exceptional clinical results but also producing exceptionally high prices. As patents expire, copies and price competition are expected throughout the world. However, due to the intrinsic heterogeneity and molecular complexity of biologic medicinal products, their copies cannot simply be authorized under the "generic rule" valid for small chemical entities. In response, a dedicated regulation was issued in the European Union. It is based on the concept of "biological medicinal products similar to a biological reference product", or "biosimilars". This book analyses the context of biotechnological production and addresses the European legal framework for biosimilar market approval. It highlights post-market authorisation issues, such as Risk Management Plans and substitution of products, and outlines some other issues, such as cost management and international nomenclature. This book is primarily intended for hospital-based physicians and pharmacists. It will also be a valuable resource for all actors from all countries who want to better understand the emergence of these new medicinal products within the European context.

Both scientifically and socially the Vlth International Symposium on Amyloidosis, August 5 - 8, 1990 in Oslo was a great success. There were three and a half intensive days. It started with the Opening Ceremony, particularly highlighted with the Norway-Norway multi media show by David Cochron, and ended with a visit to the Edvard Munch museuro and the Farewell Salmon Dinner on the evening of August 8 (not to forget the "happy birthday" song for Dorothea Zucker-Franklin at the breakfast table the following morning). In between was the intellectual penetration into the science of amyloidosis and amyloid proteins, and a deepening of many friendships among young and old "amyloidologists", together with some of the cultural and historical features of Oslo and Norway. Among the numerous Ietters of thanks and gratitude that we have received, the senior organizer of the previous meeting, Takashi lsobe said it briefly and eloquently: "You have overwhelmed us, you have performed a drama with joy and cheer, you have hosted so nicely with lovely secretariat, you have arranged impressive hospitality in every respect, you certainly did for all of us" Now we are left with the proceedings book for the three coming years until the next symposium in Kingston, Canada, which will be organized by Drs. Robert Kisilevsky and Thomas Muckle from the Department of Pathology at Queens University in 1993. The scientific contributions herein cover all the sessions of the meeting.

This second edition of the Manual of Clinical Dialysis is a concise and well-illustrated guide to all aspects of dialysis. All chapters have been revised and present a complete overview of the techniques, processes and equipment involved in clinical dialysis as well as an overview of the complications of dialysis. The manual also provides an overview of common clinical problems related to renal failure such as hypertension, anemia and renal osteodystrophy.

This book provides a concise, patient-directed approach to stone prevention. It defines who to evaluate and when to treat, and provides empiric guidelines for all stone formers. Specific treatment guidelines are also included, based on the kidney stone composition and the underlying metabolic abnormalities demonstrated by 24-hour urine stone risk profile. Written by experts in the field, Pocket Guide to Kidney Stone Prevention: Dietary and Medical Therapy serves as a valuable resource for a broad base of clinicians in primary and specialty care.

Chronic kidney disease with a worldwide prevalence of 10% in the general population is emerging as a major public health priority. Renal dysfunction is associated with a high risk for cardiovascular complications. The relationship between renal insufficiency and cardiovascular disease, termed the cardiorenal syndrome exists whether impairment of renal function is a consequence of primary renal parenchymal disease or primary heart disease. Several pathophysiologic mechanisms have been postulated to explain the relationship between renal dysfunction and cardiovascular disease. Recent studies indicate an integrated response of the vascular smooth muscles and glomerular mesangial cells to traditional and uremia related cardiovascular risk factors. Traditional risk factors can incite renal impairment and cardiac damage. As renal function deteriorates, uremia-related risk factors play an increasing role both in reduction in glomerular filtration rate and cardiovascular damage. Several uremia related factors such as uncontrolled hypertension, disturbed glucose insulin metabolism, microalbuminuria, phosphate retention, secondary hyperparathyroidism, myocardial and vascular calcification, hypertensive-uremic cardiomyopathy, inflammation, oxidant injury, and neurohormonal dysregulation have been implicated in the pathogenesis of the cardiorenal syndrome. Recent data suggest that management of the cardiorenal syndrome requires aggressive control of traditional risk factors as well novel approaches to prevent or reverse uremia -related processes. This book provides a comprehensive update analysis of our current understanding of the cardiorenal syndrome including epidemiology, pathophysiologic mechanisms, and therapeutic approaches.

In the 6 years since the publication of the first volume of Recent Advances in Endourology by the Japanese Society of Endourology and ESWL, data on long-term oncological or functional outcomes have been collected in several related fields, and advances in surgical techniques and improved instrumentation have led to further development of such complex surgery as laparoscopic partial nephrectomy and radical prostatectomy. This seventh volume in the series focuses on the treatment of urogenital malignancies by endourological procedures, including laparoscopic surgery with robotic assistance. The standard procedures and their relatively long-term outcomes as well as new techniques have been clearly described with detailed references. This book provides a better understanding of the present status of endourological management for urogenital carcinoma and sets the stage for future improvements in both oncological and functional outcomes.

This is the first textbook entirely dedicated to the endovascular treatment of complications related to arteriovenous accesses for hemodialysis (native fistulas and prosthetic grafts). The book addresses the anatomy of upper limb arteries and veins as well as the clinical presentation of patients and the way to perform and read a fistulogram. Many details and illustrations are provided, clarifying the subtleties in catheterization and the dilation of stenoses. From a strategic point of view, it is explained for the first time that many stenoses must either be ignored or deliberately underdilated. A wealth of images helps to understand the different stages of access recovery from thrombosis. As the number of incident dialysis patients is increasing by 5% every year, this is a field of growing interest. In testament to this there are several annual or bi-annual meetings held by numerous national and international societies (vascularaccesssociety.com, sfav.org, vasamd.org, dialysiscontroversies.org, asdin.org).

The prevalence of hypertension is almost three times as high as that of diabetes mellitus type 2, with both conditions being major risk factors for stroke, ischemic heart disease, cardiac arrhythmias, and heart failure. The exact prevalence of hypertension related to hormonal derangements (endocrine hypertension) is not known but estimated to affect less than 15% of hypertensive patients. Recent scientific discoveries have increased the understanding of the pathophysiologic mechanisms of hypertension. In Endocrine Hypertension, a renowned panel of experts provides a comprehensive, state-of-the-art overview of this disorder, discussing when to assign an endocrine cause in one of many conditions that may present with hypertension. The first part of Endocrine Hypertension is dedicated to adrenal causes. The second part of the volume concerns potential nonadrenal causes of hypertension, such as growth hormone excess or deficiency, primary hyperparathyroidism, vitamin D deficiency, testosterone deficiency, insulin resistance, obesity-associated hypertension, and the role of central mineralocorticoid receptors and cardiovascular disease. An important contribution to the literature, Endocrine Hypertension is an indispensable reference not only for endocrinologists, diabetologists, and adrenal investigators, but also for translational scientists and clinicians from cardiology, internal medicine, pediatrics, family medicine, geriatrics, urology, and reproductive medicine / gynecology.

This volume will be a reliable source on the management of the elderly with renal disease. There is an ever-increasing proportion of the aging population affected by renal disease and hypertension, and physicians are faced with atypical clinical presentations of renal disease in the aged as compared to younger people. This volume combines the fields of nephrology and geriatrics and presents a multidisciplinary approach to the topic.

Knowledge of the juxtaglomerular apparatus (JGA) of the kidney and of the synthesis and secretion of renin has increased to such an extent over the past few years that it is now appropriate to summarize this knowledge in a monograph on the JGA, the first of its kind. It was the authors' special concern to demonstrate the association between structure and function for renin secretion, not only within the juxtaglomerular region, but also in the region of the renal cortex beyond the JGA. The description of the pathology of the human JGA, studded with references to experimental findings but nevertheless fully self-contained, should help to make this monograph also useful for clinicians.

Though kidney transplantation is considered a routine procedure, there are still significant challenges in post-transplant management. Core Concepts in Renal Transplantation is a clinically focused authoritative guide to the management of kidney transplantation. This comprehensive, state-of-the-art reference summarizes the recent changes in the field of transplantation, offering the complete range of up-to-date information on all the various aspects of basic immunobiology and the medical care of the transplant recipient. Written by a team of renowned authorities in renal transplantation, this concise resource is intended for both the nephrologist and the non-specialist with an interest in kidney transplantation.

Stjarne: The present review puts the emphasis on two important developments: the discovery that individual postganglionic sympathetic neurons may secrete multiple transmitter substances from different classes of vesicles and by different mechanisms, and the introduction of new techniques which may permit for the first time direct impulse by impulse analysis of transmitter secretion in individual sympathetic nerve varicosities. Illes: Exogenous and endogen opioid peptides elicit a number of effects in the organism, usually by modifying the function of transmitter and hormone systems, for example, activation of multiple opioid receptors. The effects of opioids on transmitter and hormone release have frequently been reviewed. This review gives a detailed overview on the involvement of multiple opioid receptors in these processes. Rothstein: This article gives an overview of the exchange in acidification and transepithelial salt and water transfer in nonepithelial cells. Delineating the exchanger's most important, common features, and concentrating particularly on its role in cell pH and volume regulation.

Chronic Kidney Disease (CKD) is a recognized risk factor for cardiovascular events and death. The coexistence of CKD and heart failure is increasing in prevalence worldwide and requires a unique and subtle approach to patient management. The Kidney in Heart Failure focuses on the changes that occur in kidney physiology as a function of a failing heart. This comprehensive resource covers epidemiology, pathophysiology, management of kidney disorders and advances in nephropathy management. In addition, the latest therapies, common heart failure dilemmas and kidney disease markers are included. Each chapter is co-authored by a Nephrologist and Cardiologist, offering a unified perspective to these chronic conditions. This indispensible volume provides the reader with the depth-of-knowledge needed for assessing and treating the cardio renal patient.

While patients with metastatic renal cell carcinoma (mRCC) are now living longer with improved quality of life, the success of novel therapies for mRCC has created challenges for practicing oncologists. Many patients who initially respond to targeted therapies ultimately develop progressive disease due to acquired resistance to these agents. Additionally, some patients do not respond at all to any of the currently approved targeted agents, underscoring the need for continued and concerted efforts to identify other relevant targets and pursue alternative therapeutic strategies. Part of the Oxford American Oncology Library, Renal Cell Carcinoma is a concise handbook that addresses the complex management of patients with mRCC. The book begins with a review of the epidemiology, pathology, and biology of renal cell carcinoma followed by chapters on specific targeted therapies and managing complications. The final chapters discuss supportive and integrative care and emerging therapies.

This book does not pretend to be a comprehensive textbook of nephrology, nor is it a guide to the management of renal disease, as space does not allow the description or discus sion of investigation and treatment. Its intention is to illustrate the diverse diseases which present to nephrologists. Since the key to understanding the effects and progression of a disease are to know and com prehend its pathology, I have approached the subject not by discussing presenting symptoms of single diseases in different sections, which would lead to much repetition, but by describing the disorders according to the mechanisms which cause them. To illustrate the text I have chosen the most immediate clue which usually appears in a given dis ease, which may therefore be a clinical sign, a radiograph or the histological appearance of a renal biopsy. D. Gwyn Williams Guy's Hospital, London 1. Trauma Trauma is a common cause of acute renal failure. This may arise directly from injuries to the kidneys themselves despite their protected position (Figure 1). Trauma can also cause acute renal failure by damaging the renal arteries, which may be actually avulsed from the kidneys, or stretched at the time of impact, with tearing of the arterial wall and secondary thrombosis. Figure 2 shows the renal arteriogram of a young man who presented with anuric acute renal failure after a motorbike accident. Only the upper pole of the right kidney is Figure 1.

This new edition of Vascular Interventional Radiology: Current Evidence in Endovascular Surgery provides a thorough yet succinct and accessible review of the latest knowledge in the field of endovascular surgery. All chapters have been updated to reflect the advances that have occurred during the past five years, and new chapters are included on carotid artery stenting and day case intervention. The chapter on lower limb veno-occlusive disease has been expanded to include management of deep venous thrombosis. Among the other topics considered are the endovascular treatment options in different arterial territories, aneurysm repair techniques, and the management of venous stenosis and venous insufficiency. The aim throughout is to tackle issues of evidence-based practice in order to assist trainees and experienced practitioners in making and implementing treatment decisions. This book will be an invaluable source of information for both interventional radiologists and vascular surgeons with an interest in endovascular techniques.

This book provides a comprehensive look at renal cell carcinoma, exploring its biology as well as current and future molecular targets for renal cancer carcinoma.

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.

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.

A year or so after Dr. Robert Popovieh arrived in Seattle in 1965 to begin working on his doctoral thesis under Dr. A.L. Babb, we had just begun work to try to prove the prediction that the peritoneum had a higher permeability to 'middle molecules' than hemodialysis membranes [I]. Several years later, when Dr. Popovieh accepted a position at the University of Texas in Austin, he decided to concentrate his research efforts in the area of peritoneal dialysis and everyone knows how successful that effort has become [2]. Indeed, because of continuous ambulatory peritoneal dialysis (CAPD), long-term per itoneal dialysis after a two-decade incubation period is finally becoming an equal option to hemodialysis and transplantation in the management of chronic renal failure. For me this development represents final vindication of a twenty-year effort to help promote peritoneal dialysis, often in the face of enormaus opposition. I particularly remember a policy meeting at the NIH a few years back in which it was decided by my colleagues on the committee that long term peritoneal dialysis had no future and therefore no funds for projects in this area would be forthcoming. Based on the excellent results that Boen and later Tenckhoff had been getting in our Seattle program, I knew the committee was wrong and tried to convince them otherwise. Naturally, being the only favorable vote, I failed. I often wonder how many years this decision and others like it set back peritoneal dialysis.

Therapeutic regimens for visceral leishmaniasis (also Kala-azar, Dum-dum fever or black fever), caused by parasitic protozoa of the Leishmania genus, evolve at a pace never seen before. Spread by tiny and abundant sand flies, the parasite infects internal organs and bone marrow and if left untreated will almost always result in the death of the host. In developing countries successful diagnosis and treatment are complicated by asymptomatic cases, undernutrition and Kala-azar/HIV co-infections. This book brings together world-renown experts writing state-of-arts review on the progress in diagnosis and treatment of visceral leishmaniasis, ultimately leading to the complete elimination of this fatal disease from South Asia. The chapters provide valuable information for disease control as well as therapy and the diagnostic improvements necessary for early treatment, subclinical detection and drug-resistant cases. The presented methods allow for points-of-care testing in the endemic area, enabling rapid detection in resource-poor settings with easy handling and low costs. This book provides essential information for scientists, medical practitioners and policy makers involved in the diagnosis, treatment and elimination of Kala-azar.

Nocturia: Causes, Consequences and Clinical Approaches is the first volume exclusively on the topic of nocturia and is designed to be a comprehensive treatise on the subject. The volume is organized into 11 chapters first introducing and defining nocturia and its impact to patients and society, followed by chapters dealing with predictors and risk factors; relationship to sleep disorders; overactive bladder; and water homeostasis. Therapeutic areas addressing nocturia are covered in specific chapters and include pharmacotherapy affecting the bladder, prostate and kidneys as well as behavioral therapy and surgical intervention. Separate chapters are devoted to alternative therapies as well as the impact of nocturia in the elderly. The volume closes with a chapter presenting avenues for future investigation into the etiology and management of nocturia. Clinical case scenarios inclusive of figures and tables illuminate the evaluation and management of patients with nocturia. Nocturia: Causes, Consequences and Clinical Approaches will give physicians and related healthcare providers the background to understand the conditions causing nocturia, how nocturia affects society and the basis for its rational treatment. It will be used as a state of the art reference by urologists, urogynecologists, internists, nephrologists, pulmonologists, endocrinologists and sleep medicine specialists.