This book, part of the series Rare Diseases of the Immune System, offers comprehensive, up-to-date coverage of the pathophysiology and management of the antiphospholipid syndrome (APS). Immunologic and genetic aspects are discussed and the pathogenic mechanisms responsible for such phenomena as APS-mediated thrombosis and pregnancy loss/complications are explained. The main clinical manifestations, classification criteria and diagnostic tools are identified, and close attention is paid to the nature of the involvement of various organs or organ systems in APS. Specific chapters describe the treatment of the different symptoms, therapies of value in avoiding recurrences, and innovative treatment approaches. The authors are senior experts in the field who are aided by younger fellows, ensuring that the book is also educationally oriented. This handy volume will be a valuable tool for postgraduates in training and professionals wishing to extend their knowledge of this specific syndrome.

This volume of the Keio University International Symposia for Life Sciences and Medicine contains the proceedings of the 13th symposium held under the sponsorship of the Keio University Medical Science Fund. The fund was est- lished by the generous donation of the late Dr. Mitsunada Sakaguchi. The Keio University International Symposia for Life Sciences and Medicine constitute one of the core activities sponsored by the fund,of which the objective is to contribute to the international community by developing human resources, promoting scienti?c knowledge, and encouraging mutual exchange. Each year, the Committee of the International Symposia for Life Sciences and Medicine selects the most signi?cant symposium topics from applications received from the Keio medical community. The publication of the proce- ings is intended to publicize and distribute the information arising from the lively discussions of the most exciting and current issues presented during the symposium. On behalf of the Committee, I am most grateful to the late Dr. Sakaguchi, who made the series of symposia possible. We are also grateful to the prominent speakers for their contribution to this volume. In addition, we would like to acknowledge the ef?cient organizational work performed by the members of the program committee and the staff of the fund. Naoki Aikawa, M. D. , D. M. Sc. , F. A. C. S.

This book is about "Angiogenesis". A process in which new vasculature is formed from pre-existing capillaries. Angiogenesis process is associated with the proliferation and growth of both physiologically normal and neoplastic tissues, through the formation of vascular supply, essential for delivering growth requirements such as oxygen and nutrients. The book describes more than 100 genes and their key regulatory functions in the context of normal healthy condition, disease and malignancy, cancer proliferation and progression. New insights into the role of angiogenesis and the therapeutic inhibition of its regulators are investigated, due to the great potential for exploitation in the development of a novel treatment for cancer. New scientists, junior researchers and biomedical science students will find this book an invaluable introductory reference to their insight about angiogenesis and angiogenic role of more than 100 angiogenes and their role in healthy, disease and malignant conditions.

This comprehensive volume discusses the current scope of umbilical cord blood transplantation (UCBT), including recent controversies and future developments for improving clinical outcomes. Its twenty chapters introduce new applications in regenerative medicine and discuss the latest scientific, regulatory, clinical and investigational aspects of cord blood banking. Physicians from around the world provide a global collaboration which explores strategies for umbilical cord blood expansion, homing, unit selection, and combining of graft sources to improve patient outcomes. Umbilical Cord Blood Banking and Transplantation also reviews advances in pediatric UCBT for hematologic and non-hematologic disorders as well as immune recovery, which is critical to preventing infection. Finally, it compares UCBT with other graft sources in an attempt to understand the optimal graft source for the individual patient. UCBT is an important option for many patients who need a transplant but do not have a family donor or a matched unrelated donor. The collective and timely knowledge presented here is essential reading for any regenerative medicine investigator, cord blood banker, transplant laboratory scientist or clinical physician interested in improving and expanding the applications of umbilical cord blood.

This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

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.

Blood-brain barrier (BBB) breakdown leading to cerebral edema occurs in many brain diseases-such as trauma, stroke, inflammation, infection, and tumors-and is an important factor in the mortality arising from these con- tions. Despite the importance of the BBB in the pathogenesis of these diseases, the molecular mechanisms occurring at the BBB are not completely und- stood. In the last decade a number of molecules have been identified not only in endothelial cells, but also in astrocytes, pericytes, and the perivascular cells that interact with endothelium to maintain cerebral homeostasis. However, the precise cellular interactions at a molecular level in steady states and d- eases have still to be determined. The introduction of new research techniques during the last decade or so provide an opportunity to study the molecular mec- nisms occurring at the BBB in diseases. The Blood-Brain Barrier: Biology and Research Protocols provides the reader with details of selected morphologic, permeability, transport, in vitro, and molecular techniques for BBB studies, all written by experts in the field. Each part is preceded by a review that emphasizes the advantages and pitfalls of particular techniques, as well as offering much relevant current information. The techniques provided will be helpful to both beginners in BBB research and those more experienced investigators who wish to add a specific technique to those already available in their laboratories.

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.

This book provides a review of imaging techniques and applications in stem cell transplantation and other cell-based therapies. The basis of different molecular imaging techniques is explained in detail, as is the current state of interventional radiology techniques. While the whole is a comprehensive discussion, each chapter is self-sufficient enough so that each can be reviewed independently. The contributors represent years of international and cross-disciplinary expertise and perspective and are all well known in their fields. comprehensive information on the role of clinical and molecular imaging in stem cell therapy from this book reviewed in detail. Essential reading for radiologists and physicians who are interested in developing a basic understanding of stem cell imaging and applications of stem cells and cell based therapies. However, it will also be of interest to clinical scientists and researchers alike, including those involved in stem cell labeling, tracking & imaging, cancer therapy, angiogenesis and cardiac regeneration.

Multiple myeloma is the second most common hematologic malignancy and c- rently affects approximately 50,000 people in the United States. Each year about 20,000 people are diagnosed with myeloma. Although new treatments have been developed, which signi?cantly prolong the survival of patients, myeloma bone d- ease still remains a major cause of severe morbidity and increased mortality in patients with myeloma. Myeloma bone disease is characterized by "punched out" lytic lesions caused by increased osteoclastic bone destruction accompanied by suppressed or even absent osteoblast activity. Advances in our understanding of both the pathophysiology of myeloma bone disease and the development of novel agents that target speci?c pathways involved in both the increased osteoclast f- mation and the suppressed osteoblast activity in myeloma provide new hope for these patients. The treatment of myeloma bone disease was revolutionized by cl- ical trials that demonstrated the signi?cant bene?t of intravenous bisphosphonate therapy in patients with myeloma bone disease. With the identi?cation of many of the cytokines and chemokines involved in myeloma bone disease, novel th- apies such as denosumab that blocks RANKL activity, anti-DKK1, which targets the inhibition of osteoblast activity by blocking Wnt signaling inhibition, and the potential anabolic effects of agents such as bortezomib and activin have greatly improved our potential to block the progression or reverse myeloma bone disease.

This completely revised and enlarged 3rd edition continues the idea of the previous version to provide an up-to-date overview of blood and marrow transplantations. Indication to transplantation and pre-transplant considerations are discussed in detail before the transplant procedure with all acute and delayed procedure is described. An outlook on the latest developments and their future aspects is included, and problems and pre- and post-transplant complications are discussed. This book helps practising hematologists, oncologists,and other physicians as well as physicians in training and students to develop an idea as to when blood and marrow transplantation should be considered, what the costs are and how a donor can be selected.

The theory of blood circulation is one of the oldest in science, and remains a vigorous field of study with many features that have been described in physical and mathematical terms. In Biomechanics: Circulation, Fung presents a treatment of the fundamental biomechanics of the cardiovascular and pulmonary systems, using a mathematical approach to illuminate problems in experiemental design, data collection, modeling, observations, and theory. This second edition includes extensive changes incorporating major advances in hemodynamics that have occurred during the past decade. There are new chapters on coronary blood flow and skeletal muscle microcirculation. As in the first edition, Biomechanics: Circulation emphasizes the coupling of fluids and solids in the cardiovascular pulmonary systems, and consistently brings both morphology and rheology to bear on the analysis of blood flow. Numerous exercises are proposed to encourage the reader to formulate and solve problems. Together with his other two treatises on biomechanics (Biomechanics: Mechanical Properties of Living Tissue and Biomechanics: Motion, Flow, Stress and Growth), this book confirms that "although it is clear that Fung has made substantial contributions as a researcher...it can equally well be said that he is an exceptional teacher" (Quart. Rev. Biol.). Y.C. Fung is professor emeritus in the Department of Bioengineering at the University of California at San Diego.

Each chapter of this volume is a contribution from an expert in the field, chosen by the editors to contribute to the 1997 "Current Issues in Blood Substitute Research and Development" course given in San Diego, March 17-19. The contributors were selected because of their expertise in areas which the editors believe to be critical to the advancement of the field, and which reflect activity in "hot" areas of relevant research. While there is a continuity in style for the annual course, each year brings changes in emphasis and content. In previous years, we were often not able to provide time for participants to present their views and opinions. Consequently, this year we encouraged discussion after each presentation. These sessions were recorded, transcribed, and are printed with the chapters herein. We believe that the product is very close to the capturing this year's course in print, and trust readers will enjoy reading the always candid and often provocative remarks from the audience. The price paid for inclusion of the discussion transcriptions was a delay in publication. Each author was allowed to edit his/her discussion section as well as the final version of the chapters prior to publication. The changes are mainly for grammar, and we tried, when possible, not to alter the conversational style of these interchanges.

This issue of Hematology/Oncology Clinics, guest edited by Dr. Glenn J. Hanna, will focus on Head and Neck Cancer. This issue is one of six selected each year by our series consulting editors, Dr. George P. Canellos and Dr. Edward J. Benz. This issue addresses the evaluation and management of the complex head and neck cancer patient with articles focused on unique epidemiology and therapeutic principles by subsite of disease. Additional information relevant to rare head and neck malignancies is included. The issue further focuses on the evolving applications of minimally invasive surgery in oropharynx cancer and the role of immunotherapy in the management of advanced disease. Topics include: Radiologic Evaluation of the Head and Neck Cancer Patient, Robotic and Endoscopic Approaches to Head and Neck Surgery, Cancer of the Oral Cavity and Lip, Cancer of the Oropharynx and the Association with Human Papillomavirus, Cancer of the Larynx and Hypopharynx, Cancer of the Nasal Cavity and Paranasal Sinuses, Cancer of the Nasopharynx and the Association with Epstein-Barr Virus, Salivary Glands Cancers, Thyroid and Parathyroid Cancers, Cutaneous Malignancies of the Head and Neck, Managing Recurrent and Metastatic Head and Neck Cancer, and Immunotherapy for Head and Neck Cancer. Provides in-depth, clinical reviews on head and neck cancer, providing actionable insights for clinical practice. Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field; Authors synthesize and distill the latest research and practice guidelines to create these timely topic-based reviews.

David Kuter and a host of leading international researchers summarize in one volume all the knowledge of thrombopoietins (TPO) available today. The distinguished experts review the history of the search to discover TPO, describe the molecular and biological characteristics of this new molecule, and present the results of the preclinical animal experiments that will guide clinical use of this new hormone. Along the way they provide the most recent and comprehensive guide to the biology of megakaryocytes and platelets.

This monograph covers the entire field of blood group serology, with its main emphasis on the chemical and biochemical basis of blood group specificity. Full consideration is given to molecular biology investigations, in particular to studies on the structure of blood group genes and the molecular biological basis of alleles and rare blood group variants, whereby relevant literature up to the year 2000 is covered. The text is supplemented by numerous illustrations and tables, and detailed reference lists.

This volume provides a comprehensive overview of critical care of the pediatric immunocompromised hematology-oncology patient. The text focuses on unique aspects of the pediatric immunocompromised patient that predisposes the child to significant illness, and presents critical care management strategies specific to the patient population. In addition to chapters on oncology, primary immune deficiency, immunocompromised hematology, and hematopoietic cell transplant patients, the book covers the changing landscape of ICU care, pharmacologic considerations, and psychological and social aspects of the critical care of hematology-oncology patients. Written by experts from a range of disciplines, Critical Care of the Pediatric Immunocompromised Hematology/Oncology Patient: An Evidence-Based Guide is a valuable resource for clinicians and practitioners who treat this patient population.

Proceedings of a Workshop sponsored by the Commission of the European Communities as advised by the Committee on Medical and Public Health Research and the Committee on Bioengineering Evaluation of Technology Transfer and Standardization

Although blood substitutes represent a goal that has been sought for more than a century, their development is now on the cutting edge of biotechnology: beyond biochemistry and molecular biology, these products are being integrated into the larger physiological picture of gas transport that is essential to every living organism. New products will find obvious clinical application, since they overcome many of the problems with blood transfusion, such as the need to crossmatch, storage limitations, and the risk of transmission of infectious disease. As work continues to bring this new class of products to market, discoveries have been made about very basic aspects of how red blood cells work with regard to the exchange of oxygen and carbon dioxide and interactions with molecules such as nitric oxide and carbon monoxide which may mediate contractility of smooth muscle. These new challenges are being met with impressive rapidity as products are readied for testing and introduction into clinical use. As more is understood about the general properties of artificial blood substitutes, attention is focusing on applications which will benefit the most from their availability. This volume is a collection of chapters by researchers currently working in the field of blood substitutes and closely related fields. Each of them focuses on current challenges from a different perspective, from the clinical question, "What is the target?", to detailed descriptions of the interactions with nitric oxide, endotoxin, and carbon dioxide. Included in the volume is a review of the peer-reviewed research published in 1995 and a general discussion of current products and potential clinical applications. Takentogether, these chapters provide an up-to-date picture of this rapidly evolving field.