This book covers a wide range of disorders such as atrial fibrillation, artificial heart valves, deep vein thrombosis, pulmonary embolism and stroke. Handbook of Oral Anticoagulation aims to provide an accessible overview of the exciting new developments in this field. Incorporating numerous quick-reference tables and figures and fully referenced throughout to key papers and the latest reviews, it will be a useful resource for all healthcare professionals involved in thromboprophylaxis.

It was the year of 1969 when this monograph was originally published in Japanese by Professor TADASHI KAWAI, titled as "The Plasma Proteins, Their Fundamental and Clinical Aspects." After I read through the Japanese edition, I was impressed by its rather complete coverage of the subjects and their detailed descriptions. I have felt that this excellent monograph should be distributed not only among our Japanese scien tists but also among many other colleagues throughout the world. I am happy, the refore, to know that the English edition of his monograph, partly revised, is ready to be published at this time. Professor KAWAI received his postgraduate medical training in U.S.A. for seven years, and was certified by the American Board of Pathology in both Anatomical and Clinical Pathology in Fall, 1962. Thus, I believe, he is the most suitable fellow for publishing the English edition of this kind.

Since there are many different tissues and organs in the body, a study of oxygen transport to tissue necessarily involves a great diversity of bodily functions. Furthermore, these tissue functions can be approached from the viewpoint of several disciplines. Even tually, however, all of these approaches must be combined to arrive at a comprehensive picture. This multidisciplinary effort, though imperative, has been implemented slowly because traditional biologi cal science has been largely organ- or discipline oriented. Initia tives to realize an effective international multidisciplinary collab oration have assumed increasing momentum for the past 20 years. These include meetings held in Bad Oeynhausen in 1965 (book in 1968, edited by D. W. Lubbers, U. C. Luft, G. Thews and E. Witzleb), in Nijmegen in 1968 (book in 1969, edited by F. Kreuzer), in Vancouver in 1970 (J. Strauss), and in Dortmund in 1971; this last was in connection with the 25th International Physiological Congress in Munich (book in 1973, edited by M. Kessler, D. F. Bruley, L. C. Clark, Jr., D. W. Lubbers, I. A. Silver and J. Strauss). This increasing international cooperation called for a more formal organization of these individual initiatives. The credit for taking this decisive step goes to H. I. Bicher and D. F. Bruley from the U. S. A. and D. W. Lubbers and M. Kessler from Germany, who got together in 1972 to plan a large-scale inter national meeting and to organize an international society."

Before the introduction of DDA VP, centrnl diabetes insipidus was treated by the administration of a more or less purified extract from bovine or porcine posterior pituitaries, and the prepamtions were mostly given in the form of nasal snuff. In 1956, the structure of vasopressin became known and two forms were found, namely arginine vasopressin (A VP) in humans and most other species, and lysine vasopressin (L VP) which was found in the pig. In 1967, Zaornl et al. were the frrst to synthesize l-desamino-8-D-arginine vasopressin, DDA VP. In comparison with the compounds which were previously available, DDA VP offered increased antidiuretic potency and an equally distinct shift of the antidiuretic to pressor potency rntio. As a result of the pioneering studies of Cash and Mannucci, numerous publications appeared in the medical literature of the 80's, widening the fields of clinical application of the drug. A very important aspect of this drug is that it can be used as an alternative treatment for mild factor VllI deficiencies, mild hemophilia A and von Willebrnnd's disease. These congenital deficiencies are far from mre and have, up to now, been treated with plasma-derived factor VIII concentrates; in the countries in which desmopressin has not been used a consistent proportion of these patients have seroconverted for HIV 1 and hepatitis.

The book combines general concepts and methods to investigate calcium signalling in cells ranging from molecular biology approaches to manipulation of calcium in living cells. The focus within these methods in on the broad range of fluorescence imaging technology, in particular on optical sectioning techniques and fast image acquisition. In addition to these general guidelines there are application examples in a context beyond calcium signalling in two major fields: investigations of isolated cardiac myocytes and red blood cell related research. While the cellular cardiology section provides snapshots of certain calcium signalling aspects, the red blood cell part presents an overview from the functional identification of calcium-channels to a concept of physiological and pathophysiological relevance.

150 years after the first description of the clinical picture of "white blood" and the introduction of the term "leukemia" by R. Virchow it appears, that the leukemias, and the acute leukemias in particular, serve as an impressive example for the major improvements that have been achieved in the treatment but also in the understand ing of the biology of malignant dis orders. The international symposia "Acute Leukemia" which are held at Munster since 1986 have developed into an interna tional forum to review the current progress and the future perspectives of leukemia research and therapy at a high scientific and clinicallevel. Since the possibility for active participation in these symposia is somewhat restricted we are glad to have the opportunity to extend the information that was presented at the symposium "Acute Leukemias V - Experimental Approaches and Management of Refractory Disease" which was held from February 27 to March 2, 1994 to a broader audience of basic scientists and clinicians. This meeting was especiaIly designed to discuss experimen tal approaches and the management of refractory disease which allows to evaluate new experimental therapies on the basis of preclinical studies."

Oncology has developed as a subspecialty of medicine with unique and often complex clinical problems. This handbook ofhematologic and oncologic emer gencies provides a compact, concise, yet comprehensive guide to the manage ment of a variety of difficult clinical situations. The authors of the various chapters are all clinicians with experience in the management of these difficult patients. Their efforts provide insight and a ready source of practical infor mation which lends itself to use in the clinic and in the inpatient ward. The authors sincerely hope that this handbook will be of service to house officers and fellows alike, as they develop skills in the management of the emergent problems of patients with hematologic and other neoplasms. Janice P. Dutcher Peter H. Wiernik Bronx, New York;; Contents 1. Syndrome of Inappropriate Antidiuretic Hormone Secretion and Hyponatremia . . . . . . . . . . . . . . . . . . . . . . . . 000 . . . . . . . . . . . Stuart L. Marcus, M.D., Ph.D., and Joachim Z. Fuks, M.D. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3. Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. Acute Tumor Lysis Syndrome: Prevention and Management . . 9 Stuart L. Marcus, M.D., Ph.D., and Avi I. Einz;ig, M.D. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2. Risk Factors for the Development of Azotemia in Acute Tumor Lysis Syndrome........................................... 10 3. Metabolic Abnormalities That Occur during Acute Tumor Lysis Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 . . . . . . . . . . . . . . 4. Prevention of Acute Tumor Lysis Syndrome: Management prior to Beginning Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . 5. Posttreatment Management: Indications for Dialysis . . . . . . . . . . 14 . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 . . . . . . . . . . . . . ."

In September 1998 experts from 19 countries came together for an interdisciplinary discussion of the function of animal peroxidases, a family of enzymes embracing myeloperoxidase, eosinophil peroxidase, thyroid peroxidase and lactoperoxidase. Their papers have been updated for publication, yielding a wide-ranging overview of the state of the art. The chapters cover a wide range of topics, including three-dimensional structure of representative family members, their biosynthesis and intracellular transport, mechanism of action as well as applications to clinical medicine. They are of clinical relevance in, for example, arteriosclerosis, multiple sclerosis, infections, tumorigenesis, rheumatic diseases and hypothyroidism. This book forms an excellent introduction for anyone interested in the peroxidase family of enzymes.

The International Workshop - Conference on Atherosclerosis was held at the University of Western Ontario, London, Ontario, Canada, September 1 - 3, 1975. This book does not represent in a strict sense the entire proceedings of the above Workshop - Conference, but does reflect largely the format and the essential content of the scientific sessions. Thus, each of the three Sections of the book is comprised of the summarized presentations either at the Plenary Sessions (Section I), Proffered Papers (Section II) or Workshops (Section III). Section I comprises all the presentations of the Plenary Session on September 1 and the first three presentations at the Plenary Session on the last day of the Conference (September 3). The remaining two addresses of the latter Session (Resume of Workshop - Conference and Closing Remarks) follow the Section III at the end of the book. Sections II and III are subdivided into Chapters which correspond to the individual Sessions of Proffered Papers and Workshops, respectively. To facilitate the orientation, particularly for those who attended the Workshop - Conference, a Summary Table of all Sessions of Proffered Papers designated as Chapters in this book, precedes Section II, and a similar Summary Table of Workshops, also designated as Chapters, precedes Section III. The Tables include, in addition, the names of both Chairmen of each Session. The Chairmen whose names do not appear on either Summary Table are those who chaired the two Plenary Sessions, i. e.

This volume contains those papers which were presented at the Second International Symposium on Oxygen Transport to Tissue, to- gether with the discussions which followed. These discussions were generously summarized by the chairmen of the various sessions. This symposium in Mainz was the third international meeting, after those held in Dortmund in 1971 and Charleston-Clemson in 1973, which dealt primarily with problems relating to oxygen transport to tissue under physiological and pathophysiological conditions. It was the second symposium conducted by the International Society on Oxygen Transport to Tissue which was founded in 1973. We dedicate this volume to the memory of the first president of the International Society on Oxygen Transport to Tissue, Dr. Mel- vin H. Knisely. July, 1975 JUrgen Grote Daniel D. Reneau Gerhard Thews Contents Welcome xxi G. Thews Session I - OXYGEN MEASUREMENTS IN BLOOD AND TISSUE A Method for Simultaneous Measurements of Bioelectric Activity and Local Tissue P02 in the CNS * * . * ...* * . * 3 A. Lehmenkuhler, H. Caspers, and E. -J. Speckmann Oxygen Fields Induced by Recessed and Needle Oxygen Microelectrodes in Ho- geneous Media * . * . * 9 G. Schneiderman and T. K. Goldstick The Application of Histological Analysis for the Localization of Tissue P02 and Local Blood Flow with the Example of the Glomus Caroticum of the Rabbit (Oryctolagus cuniculus) . . * * ...* * * . . * . * . . * . 17 H. Weigelt, E. Seidl, H. Acker, and D. W.

Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc.

Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more and more answers every day.

"Stem Cells and Tissue Engineering" is a concise review on the functional, phenotypic, regenerative, transplantational and curative aspects of a stem cell's entity. It is critical and encouraging at the same time, providing truthful and appropriate samples from the practice and research that can lead toward optimal use of this immense source of adjuvant and curative therapy in human pathology. Written by a clinician and a researcher, who are currently teaching what they are doing, it is recommended as a teaching tool along with an original textbook.

The International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis was held in Academia Sinica, Taipei, Taiwan, Republic of China, on August 30 - September 1, 1989. This Symposium has provided a forum for the free exchange of information in this important and rapidly advancing research field. This proceedings volume provides a published record of 46 papers presented at the Symposium. The sponsors have exerted no influence on the scientific opinions or positions of the participants in the Symposium. It is hoped that this Symposium will stimulate further worldwide cooperation and collaboration in these vital fields for the benefit of all human kind. This volume is composed of four parts. The first part consists of 8 papers on Fibrinogen and Fibrin: Biochemistry, Molecular Biology, and Physiology. The second part contains 16 papers on Coagulation and Fibrinolysis: Biochemistry, Molecular Biology, and Physiology. The third part has 10 papers on Cardiovascular Cell Biology: Biochemistry, Molecular Biology, and Physiology. The fourth part comprises 12 papers on Clinical Studies of the Cardiovascular System: Thrombotic and Bleeding Disorders and Thrombolytic Therapy. The Author Index with addresses of all contributors and the Subject Index of all 46 papers are arranged at the end of this volume.

Leading transplant physicians critically review and interpret twenty-one key clinical challenges in bone marrow/hematopoietic cell transplantation, and offer their best personal recommendations for treatment. Topics range from transplant strategies to complications of bone marrow transplantation, including a discussion of the indications, benefits, and the risks for a variety of leukemias, lymphomas, and solid tumors. The authors debate such contentious issues as the appropriateness of transplants in older patients, how many stem cells are sufficient for engraftment, and the pros and cons of umbilical cord blood transplantation. Up-to-date and clinically focused, Current Controversies in Bone Marrow Transplantation offers clinical oncologists, hematology/oncology fellows in training, and residents in internal medicine today's best ready reference and management guide for all their critical oncologic problems arising from the use of bone marrow/stem cell transplantation.

Hemorrhage and thrombosis are major hazards for pregnant women and their newborn infants. This book is concerned with the developmental mechanisms, the diagnosis and treatment, as well as the prevention of these hemorrhagic and thrombotic disorders. The topics discussed in this volume, (1) perinatal hemorrhage in mothers and their offspring; (2) coagulation disorders complicating pregnancy; (3) neonatal intracranial hemorrhage; and, (4) vitamin K deficiency in the neonate, will help bridge the gap between basic scientists and clinicians and between the pediatri- cian and the obstetrician. Hopefully, all those concerned with preventing these disorders will be stimulated by the information and questions raised in the fol- lowing presentations. Acknowledgements We wish to thank Professors Takeshi Abe (Vice President, Teikyo University), Nobuyoshi Shinagawa (Hirosaki University), Hiroaki Soma (Tokyo Medical College), Tamotsu Miyazaki and Keisuke Sakurada (Hokkaido University) for their helpful advice. SHIGENORI SUZUKI WILLIAM E. HATHAWAY JOHN BONNAR ANTON H. SUTOR SHIGENORI SUZUKI. * 1936 in Sapporo, Japan. M.D., Uni- 'versity of Hokkaido, 1963. Lecturer, Hokkaido Univer- sity, 1974. Alexander Humboldt-Foundation Scholarship, Free University of Berlin. University of Munich, 1974- 1976. Foriner President, Japanese Society of Obstetrical, Gynecological, and Neonatal Hematology. President of International Symposium on Perinatal Thrombosis and Hemostasis (1989 Sapporo). Professor, College of Medi- cal Technology affiliated with Hokkaido University since 1983. WILLIAM E. HATHAWAY. * 1929 in Oklahoma, USA.

The book provides a comprehensive overview of the current state, and the new concepts for the future directions of modern cancer therapy. Bringing together all the relevant aspects from basic and applied science, and the clinical experiences of this new direction in medicine, it is an up-to-date summary of the activities in the field and will be the basis for evaluating future progress in this area.

th It is a great pleasure for me to open the jubilee 25 International Symposium on Blood Transfusion here in Groningen. This symposium is co-sponsored by the World Health Organization and is being held under the auspices of the ISBT and the Secretary General of the Council of Europe, Mr Walter Schwimmer. The patronage was granted with great pleasure for several reasons. First of all, Dutch experts are very active in our Committees and have largely contributed in developing the Council of Europe principles in the blood area. Secondly, the Council of Europe is active today in the area of blood transfusion due to a tragic event, which occurred in 1953 in the Netherlands; following a flooding many of the blood products given for assistance' could not be used due to incompatibilities and differences in labelling. Some words to present the Council of Europe since the organisation is sometimes confused with institutions ofthe European Union: The organisation has been founded in 1949 to establish the principles of democracy and rule of law all over Europe. Since 1989, the year of the fall of the Berlin wall and the opening up of the iron curtain, these principles could be extended to the countries of Central and Eastern Europe. Today this makes the Council of Europe the only pan-European organisation with 41 Member States thus representing more than 750 million people.

Two infonnal meetings of consultants expert in hemostatic phenomena and in atherogenesis were held in Bethesda, Maryland, in December 1975 and February 1976 by the National Heart, Lung, and Blood Institute. Their purpose was to discuss the current status of knowledge concerning the thrombotic process in the pathogenesis of atherosclerosis. It was readily agreed that thrombosis often played a major role in plaque building and in plaque complication. It was also commented, however, that the data were qualitative in nature and that quantitative infonnation was remarkably sparse. The term thromboatherogenesis was thought to be appropriate for those phenomena in which the full expression of the thrombotic process is manifest. At the same time, recent research was noted in which what appears to be an important pathway for the initiation of atherogenesis arises from the reaction of platelets with injured arterial endothelium and'Subendothelium without necessarily involving the complete classical thrombotic process. A name was not coined for this circumstance, but it was held that thromboatherogenesis was not a fully appropriate one.

The provocative title stems from the recent International Blood Transfusion Symposium in Groningen, The Netherlands held under the auspicies of the World Health Organization (WHO), International Society of Blood Transfusion (ISBT) and Council of Europe (CoE). Transfusion medicine is a new discipline which has a wide remit. As defined recently, transfusion medicine deals with that part of the healthcare system which undertakes appropriate provision and use of human blood resources; transfusion practice is therefore a collective activity linking the blood donor with the patient. Transfusion medicine occupies areas in which it is deemed to be important or even essential that medical practitioners contribute to this bridging process. The broad issues and complex practices are presented in the masterly Introduction by the WHO's Assistant Director General with emphasis on education and multidisciplinary facets involving transfusion medicine. The challenging subjects are dealt in great details with a wealth of personal experience by 24 experts from the U.K., France, The Netherlands, U.S.A., Australia, Germany, Sweden, WHO and the Council of Europe.This is a comprehensive yet concise state of the art presentation involving donor and delivery system, ethics and legal elements, effects of modern techniques, importance of management and the future directions in this new economic environment. The book has been divided into four sections which discuss both the facts and the fiction.

A variety of metabolic processes are known to be intimately involved in the maintenance of cellular structure and function. It has also become clear that metabolic events involved in the synthesis and hydrolysis of ATP as well as for the synthesis of proteins and phospholipids are essential for cellular health. The regulation of cell function is generally achieved through participation of a wide variety of hormones and different signal transduction mechanisms for the activation/deactivation of some specific metabolic processes. In this regard cyclic AMP and calcium seem to play a crucial role. Various hormones are also known to affect the genetic machinery of all the cell; however, the exact signals for genetic control of cellular function are not well defined. In particular, the sequence of events concerned with remodelling of different types of cells under various pathological situations is poorly understood. In this book we have therefore dealt with some of these issues from biochemical, molecular biological, physiological, and pharmacological viewpoints. Special emphasis has been laid on understanding heart function and metabolism in health and disease in general, and cardiac hypertrophy, heart failure, and ischemic heart disease in particular. It is hoped that this multidisciplinary information will be of value to basic scientists and clinical investigators.

This book offers a description of current and recently developed laboratory assays in the field of haemostasis and thrombosis. It is the result of a unique cooperation between experts from more than 60 institutes in 12 European countries, brought together by the ECA T (European Concerted Action on Thrombosis and Disabilities) under the auspices of the Commission of the European Communities in Brussels, Belgium. The ECAT, which was initiated in 1981, designed and performed three prospective clinical studies to establish haemostatic factors as risk indicators of thrombosis. Included were patients with angina pectoris at risk from myocardial infarction, patients undergoing angioplasty at risk from re-stenosis, and patients receiving hip replacement at risk from deep venous thrombosis. Assay procedures were chosen, training courses for technicians held, and essential reagents were supplied from a central source. A quality control assessment scheme served to compare assay results both within and between laboratories. In the angina pectoris study, centres determined most of the assays locally; in the other two studies assays were performed centrally. The need for further quality assessment in Europe Dr J. F. Davidson in Glasgow, led to a separate activity coordinated by including coagulation inhibitors and plasminogen as risk factors for familial venous thrombosis. The Editors hope the ECA T Assay Procedures book will contribute to further harmonization ofhaemostasis assays, and ultimately to their standardization.

The aim of the issue is to describe and explain the importance of the chemokine system in hematology. The chemokine system is probably important for many aspects of normal as well as malignant hematopoiesis. A major focus is the development and treatment of hematologic malignancies, including the immunobiology of stem cell transplantation. The present reviews illustrate that chemokines can be involved in leukemogenesis. The chemokine system is also important both for the crosstalk between malignant cells and their neighbouring nonmalignant stromal cells (including endothelial cells) as well as for immunoregulation in patients treated with allogeneic stem cell transplantation. Thus, chemokines are important both for the pathogenesis and treatment of hematological diseases.

A description of the latest methods of oncological and hematological diagnostics, such as immunological, molecular genetic and histological essays. All methods are described in principle in their different variations and compared with regard to their effectiveness and cost. Written for scientists, clinicians and personnel in research, specialised and routine diagnostic laboratories in hospitals, this book satisfies the increased demand for information on new methods in hematology and oncology.

The hematopoietic system plays roles that are crucial for survival of the host: delivery of oxygen to tissues, arrest of accidental blood leaking from blood vessels, and fending off of invading microbes by humoral, cell-mediated, and phagocytic immunity. The activity of the hematopoietic system is staggering: daily, a normal adult produces approximately 2.5 billion erythrocytes, 2.5 billion platelets, and 1 billion granulocytes per kilogram of body weight. This production is adjusted in a timely fashion to changes in actual needs and can vary from nearly none to many times the normal rate depending on needs which vary from day to day, or even minute to minute. In response to a variety of stimuli, the cellular components of the blood are promptly increased or decreased in production to maintain appropriate numbers to optimally protect the host from hypoxia, infection, and hemorrhage. How does this all happen and happen without over or under responding? There has been extraordinary growth in our understanding ofhematopoiesis over the last two decades. Occupying center stage is the pluripotent stern cell and its progeny. Hematopoietic stern cells have been characterized by their capacity for self renewal and their ability to proliferate and differentiate along multiple lineages. Few in number, the stern cell gives rise to all circulating neutrophils, erythrocytes, lymphoid cells, and platelets. In hematopoietic transplantation, the stern cell is capable of restoring long-term hematopoiesis in a lethally irradiated host.

Transfusion medicine provides an excellent bridge connecting the healthy community donors with the patient's needs at the bedside; the dominant philosophy has been on patient care and science, but it is now realised that blood banks manufacture increasing amounts of blood components to administer to patients -- a role analogous to manufacturing functions. The concept of Good Manufacturing Practice (GMP) is therefore relatively new. While quality has always been important, the impact of GMP, Total Quality Management (TQM) and Quality Assurance (QA) will be profound. As the regulatory agencies, like the FDA in the U.S.A. and the EEC Commission in Europe, increase their enforcement activities, doctors, technical experts and managers will have to face many issues of quality assurance including documentation, validation, audit system, regulatory laws, licensing, teaching and training of staff and their job descriptions, standards, processing facilities, procedure validations, automation, record keeping, internal and external quality control of products and their release.The expansion of this philosophy to include Good Clinical Practice (GCP) is an even greater challenge demanding consensus therapy protocols and quality management of transfusion through auditing by the hospital transfusion committees. Such comprehensive plans will profoundly affect the financial and organisational structure of blood transfusion in the future.