This Brief provides a comprehensive introduction to the control of blood flow in the brain. Beginning with the basic physiology of autoregulation, the author goes on to discuss measurement techniques, mathematical models, methods of analysis, and relevant clinical conditions, all within this single volume. The author draws together this disparate field, and lays the groundwork for future research directions. The text gives an up-to-date review of the state of the art in cerebral autoregulation, which is particularly relevant as cerebral autoregulation moves from the laboratory to the bedside. Cerebral Autoregulation will be useful to researchers in the physical sciences such as mathematical biology, medical physics, and biomedical engineering whose work is concerned with the brain. Researchers in the medical sciences and clinicians dealing with the brain and blood flow, as well as industry professionals developing techniques such as ultrasound, MRI, and CT will also find this Brief of interest.

There have been many changes in the field of coagulation during the past decade. New concepts of epidemiology of risk factors for thrombosis now help clinicians predict who is more likely to form clots after surgery, or after being placed on oral contraceptives. New anticoagulants have the potential to redefine how patients with atrial fibrillation and venous thrombosis are managed. There are new forms of recombinant clotting factors which have changed our approach to hypofibrinogenemia and von Willebrand's disease. Newer antiplatelet agents are available and their use in patients receiving cardiac stents has mushroomed. The management of thrombosis in the setting of pregnancy has changed over the past decade, as well as the way clinicians approach women with multiple miscarriages. An entire new class of compounds, the thrombopoietins, are available to treat individuals with immune thrombocytopenic purpura (ITP). The Coagulation Consult covers major topics of interest to hematologists who are asked to consult on individuals with coagulation related diseases, and encompasses the field's most recent developments. This "case-directed" book describes state-of-the-art approaches to patients with bleeding and clotting disorders, as well as laboratory tests for coagulation. Chapters include different vignettes, focus on typical clinical consult questions, and lay out specific types of treatment. Practicing clinicians being confronted with coagulation consult students, residents, fellows and attending physicians will find this unique text an invaluable resource for some of the newer areas of coagulation science, therapy and pharmacology.

New techniques to study cell signaling and function can develop at a staggering pace; however, many approaches are as valid today as on the day they were established. Thus, the main aim of Platelets and Megakaryocytes: Volume 3, Additional Protocols and Perspectives is to complement the first two volumes published in 2004 by adding recently developed state of the art techniques. Conveniently divided into three sections, this detailed volume covers techniques to study platelet function, approaches to investigate megakaryocyte function, and perspectives on important overall concepts in the field of megakaryocyte and platelet biology. Written in the highly successful Methods in Molecular Biology (TM) series format, methods chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Platelets and Megakaryocytes: Volume 3, Additional Protocols and Perspectives adds a wealth of new expertise for the labs of scientists working in this key biological area of study.

In the last decade, there has been a remarkable explosion of knowledge in hematologic cancer from basic molecular biology and pathology to clinical therapy. This has led to many new advance and insights in the understanding of pathobiology of malignant hematology. New knowledge of disease molecular pathology, cytogenetic, epigenetic and genomic alterations have provided new strategies to attack and eradicate tumor cells at molecular level and significantly impacted our current therapeutics for hematological malignancies. The recent and ongoing rapid expansion of knowledge in this area has become extensive, dynamic and diffuse over the literature and research publications. This has led to the need to capture and compile the new and current information about hematologic cancer with special emphasis on translation from molecular pathobiology to targeted therapeutics. In this book experts from around the world share their thoughts and knowledge about the pathobiology of hematologic cancer, as well as their view on current treatment approaches and future development in these malignant hematologic diseases. This book is well suited for hematology residents, fellows and hematology-oncology physicians, hematopathologist as well as basic research scientist in the area of hematologic malignancies.

In the last decade, technical improvements have changed the inventory of many research laboratories. New techniques and discoveries continuously give rise to observations that result in the de?nition of new research objectives. In the past, - search departments were clearly demarcated. Nowadays, technology that is shared by all lines of research stimulates convergence of research interests. This also - plies to cardiovascular research. Vascular occlusive disease is now core business for researchers employed by cardiology, vascular surgery, vascular medicine, - diology, cell biology, chemistry, physiology, and many other areas. Knowledge on actual research development is shared by researchers with different skills. It is sometimes dif?cult to acquire expertise when a researcher feels his experimental work could be improved by introducing a new research technique. In this book, the investigator will ?nd an overview of recent developments that are relevant for research in general but cardiovascular research in particular. Genomics, p- teomics, microarray, RNAi, stem cells, and progenitor cells are just some phrases that have become increasingly prevalent in literature in the last few years and that are recognized by many, but are fully understood by few. In this book, experts share the most appreciated new developments and techniques in cardiovascular research. We hope that this book will help the reader who is working in the ?eld of cardiovascular research to understand and critically appreciate current research, and that it will help improve the quality of experimental work. Dr G.

This handbook offers timely investigation of current pharmaceutical trends, clinical guidelines, novel treatments, and ongoing pipeline developments, including ground-breaking advances in the use of novel oral anticoagulants. Atrial fibrillation (AF) affects an estimated 1-2% of the population and is the most common cause of sustained cardiac arrhythmia. Critically, the number of patients developing AF is expected to double in the next five decades, leading to increased incidence of stroke, heart failure and other serious thromboembolic events.

Hormone Receptors in Breast Cancer provides an up-to-date resource of the role of hormone receptors in breast cancer written in depth for both the basic molecular academic researcher and translational scientist. Advances in basic science of molecular endocrinology have undoubtedly been translated into clinical practice, and clinicians caring for this disease need to be knowledgeable about these developments. The molecular basis of hormone action has been elucidated, and the relative significance of the different estrogen and progesterone receptor isoforms has been explored. This explosion of information has lead to exciting new areas of gene specific targeting of the disease, and breast cancer prevention. Paradigm shifts in treatment options and sequencing have recently occurred in breast cancer management, necessitating close cooperation and communication between translational scientists and physicians. This book is focused on providing this communication.

This book provides a state-of-the-art approach to the molecular basis of hematologic diseases and its translation into improved diagnostics and novel therapeutic strategies. Several representative hemato-oncologic malignancies are analyzed in detail: acute lymphoblastic leukemia, acute myeloid leukemia, B-cell Non-Hodgkin lymphomas, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. Experts in the field describe the molecular methods applied for modern diagnostics and therapies, such as hematopoietic stem cell transplantation, donor recipient matching, banking of biological material, analyses of post-transplant chimerism, and minimal residual disease monitoring. The volume concludes with an extensive section comprising thorough step-by-step protocols of molecular techniques in hematology, all of them validated in the authors' own laboratories.

This book details the anatomy and physiology of the lymphovascular system as well as describes the mechanisms of metastasis. It provides readers with an understanding of immune responses of draining lymph nodes against cancer. Coverage also explains the rationale of adopting molecular therapeutics against growth factor receptors, apoptotic factors, signaling pathways and angiogenesis.

JAK tyrosine kinases and STAT transcription factors constitute a signaling pathway, which is activated by cytokines. By activating gene transcription it regulates essential biological responses to environmental cues. The Jak-Stat pathway is involved in the regulation of cell development, differentiation, proliferation and apoptosis. Improper function may contribute to hematopoietic malignancies and cancer. This book provides comprehensive insights into the latest basic and clinical developments in the field. The first part reviews recent findings and new technologies pertaining to basics of Jak-Stat function. The second part describes the evolution of Jak-Stat signaling and the role of the pathway in invertebrate organisms. The third part focuses on Jak-Stat signaling in hematopoietic cells under both physiological and pathophysiological conditions. Finally, chapters in the fourth section describe the relationship of Jak-Stat signaling to various states of disease, particularly infection, leukemias and solid cancers. The book is intended for all scientists in molecular biology, biochemistry and cell biology dealing with biomedical issues.

Sjoegren's Syndrome is slowly being recognised as one of the most common auto-immune diseases, and considered pivotal in the spectrum of auto-immune disorders. Sjoegren's Syndrome in Clinical Practice is a unique, concise book which explores important insights into Sjoegren's links with other conditions and devotes itself to shedding new light on this disease. Aimed at young medics but also suitable for the informed lay reader, physicians and pharma, Sjoegren's Syndrome in Clinical Practice will help with the diagnosis and treatment of this increasingly recognised disorder.

Heparins remain amongst the most commonly used drugs in clinical practice. Almost 100 years have passed since the initial discovery of this complex substance and, during this time, understanding of the nature and uses of heparin and related molecules has grown dramatically. The aim of this volume is to summarise the developments that have led to the current status of both heparins as drugs and the field of heparin research, with a focus on the particularly rapid progress that has been made over the past three decades. Individual sections are dedicated to the nature of heparin as a biological molecule, the current approaches and techniques that are used to ensure the safety and reliability of heparin as a medicine, the clinical pharmacology of heparin as an anticoagulant drug, effects and potential applications of heparin aside of those involving haemostasis and, finally, the nature and potential uses of heparin-like materials from both natural and synthetic sources.

Pulmonary embolism is a common but vexing illness. This book provides a contemporary overview of the most important issues from a Western and a Japanese perspective, providing the reader with state-of-the-art knowledge of the epidemiology and molecular biology of the disease. In the Diagnosis section, the relationship between venous thrombosis and pulmonary embolism is explored, and exciting new findings are presented in the fields of echocardiography and magnetic resonance imaging. The Management section focuses on surgical intervention with acute embolectomy as well as updating thromboendarterectomy for chronic pulmonary embolism. The importance of primary and secondary prevention is emphasized in chapters addressing low molecular weight heparin and the inferior vena cava filter. This cutting-edge book is a valuable resource for practicing physicians, researchers, and students in internal medicine, hematology, pulmonary critical care, and vascular medicine.

Coagulation in Cancer informs professionals working in the field of cancer about the pathophysiologic mechanisms of cancer-related thrombosis and bleeding. It provides assistance in recognizing the various bleeding and clotting disorders associated with cancer and includes current recommendations for the management of hemorrhage, and prevention and treatment of thrombosis in the patient with malignancy. This volume is a valuable addition to the literature on cancer and coagulation.

Due to its rapid development in recent years, hematopathology has become a very complicated discipline. The current development is mainly in two aspects: the new classification of lymphomas and leukemias and the new techniques. The Revised European-American Classification of Lymphoid Neoplasms (REAL classification) and the World Health Organization (WHO) classification of hematologic neoplasms require not only morphologic criteria but also immunophenotyping and molecular genetics for the diagnosis of hematologic tumors. Immunophenotyping is performed by either flow cytometry or immunohistochemistry. There are many new monoclonal antibodies and new equipments accumulated in recent years that make immunophenotyping more or more accurate and helpful. There are even more new techniques invented in recent years in the field of molecular genetics. In cytogenetics, the conventional karyotype is supplemented and partly replaced by the fluorescence in situ hybridization (FISH) technique. The current development of gene expression profiling is even more powerful in terms of subtyping the hematologic tumors, which may help guiding the treatment and predict the prognosis. In molecular biology, the tedious Southern blotting technique is largely replaced by polymerase chain reaction (PCR). The recent development in reverse-transcriptase PCR and quantitative PCR makes these techniques even more versatile. Because of these new developments, hematopathology has become too complicated to handle by a general pathologist. Many hospitals have to hire a newly trained hematopathologist to oversee peripheral blood, bone marrow and lymph node examinations. These young hematopathologists are geared to the new techniques, but most of them are inexperienced in morphology. No matter how well-trained a hematopathologist is, he or she still needs to see enough cases so that they can recognize the morphology and use the new techniques to substantiate the diagnosis. In other words, morphology is still the basis for the diagnosis of lymphomas and leukemias. Therefore, a good color atlas is the most helpful tool for these young hematopathologists and for the surgical pathologists who may encounter a few cases of hematologic tumors from time to time. In a busy daily practice, it is difficult to refer to a comprehensive hematologic textbook all the time. There are a few hematologic color atlases on the market to show the morphology of the normal blood cells and hematologic tumor cells. These books are helpful but not enough, because tumor cell morphology is variable from case to case and different kinds of tumor cells may look alike and need to be differentiated by other parameters. The best way to learn morphology is through the format of clinical case study. This format is also consistent with the daily practice of hematopathologists and with the pattern in all the specialty board examinations. Therefore, it is a good learning tool for the pathology residents, hematology fellows as well as medical students. This proposed book will present 83 clinical cases with clinical history, morphology of the original specimen and a list of differential diagnoses. This is followed by further testing with pictures to show the test results. At the end, a correct diagnosis is rendered with subsequent brief discussion on how the diagnosis is achieved. A few useful references will be cited and a table will be provided for differential diagnosis in some cases. The major emphasis is the provision of 500 color photos of peripheral blood smears, bone marrow aspirates, core biopsy, lymph node biopsy and biopsies of other solid organs that are involved with lymphomas and leukemias. Pictures of other diagnostic parameters, such as flow cytometric histograms, immunohistochemical stains, cytogenetic karyotypes, fluorescence in situ hybridization and polymerase chain reaction, will also be included. A comprehensive approach with consideration of clinical, morphologic, immunophenotypic and molecular genetic aspects is the best way to achieve a correct diagnosis. After reading this book, the reader will learn to make a diagnosis not only based on the morphology alone but also in conjunction with other parameters.

Phase I trials are a critical first step in the study of novel cancer therapeutic approaches. Their primary goals are to identify the recommended dose, schedule and pharmacologic behavior of new agents or new combinations of agents and to describe the adverse effects of treatment. In cancer therapeutics, such studies have particular challenges. Due to the nature of the effects of treatment, most such studies are conducted in patients with advanced malignancy, rather than in healthy volunteers. Further, the endpoints of these trials are usually measures adverse effects rather than molecular target or anti-tumor effects. These factors render the design, conduct, analysis and ethical aspects of phase I cancer trials unique. As the only comprehensive book on this topic, Phase I Cancer Clinical Trials is a useful resource for oncology trainees or specialists interested in understanding cancer drug development. New to this edition are chapters on Phase 0 Trials and Immunotherapeutics, and updated information on the process, pitfalls, and logistics of Phase I Trials

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.

From the world renowned Fred Hutchinson Cancer Research Center, this book is written for all physicians who treat patients with acute or chronic leukemias or myelodysplasia. It is designed to answer questions about treatment approaches that commonly arise in day-to-day practice. In keeping with the Center's groundbreaking research in bone marrow transplantation, the book provides exceptional coverage of the role of allogeneic transplant in treatment. It also addresses the important issues of supportive care and long-term complications of successful treatment. *Edited and written by experts at the Fred Hutchinson Cancer Research Center *Clinically focused and comprehensive coverage of treatment approaches *Allogeneic transplant addressed in detail *Separate chapters on supportive care and long-term complications

In this thoroughly revised and expanded third edition of the highly praised classic, The Principles of Clinical Cytogenetics, a panel of hands-on experts update their descriptions of the basic concepts and interpretations involved in chromosome analysis to include the many advances that have occurred in the field. Among the highlights are a full chapter devoted to advances in chromosome microarray, soon to become a standard of care in this field, as well as an update on chromosome nomenclature as reflected in ISCN 2009. Other features include an update on automation to reflect the current state of the art, an update on hematopoietic neoplasms to reflect the new WHO guidelines, and updates on all regulatory changes that have been implemented. Cutting edge and readily accessible, The Principles of Clinical Cytogenetics, Third Edition offers physicians who depend on the cytogenetics laboratory for the diagnosis of their patients, students in cytogenetics programs, graduate and medical students studying for board examinations, cytogenetics technologists, and cytogeneticists a clear understanding of what happens in the cytogenetics laboratory to facilitate accurate and timely diagnoses.

We are pleased to present our readers the proceedings of the International symposium on "New Aspects of Human Polymorpho- nuclear Leukocytes" which was held in Freiburg im Breisgau, FRG, from October 26-28th, 1989. The meeting provided an unique framework for close interaction between scientists from various disciplines, including bioche- mistry, biology, physiology, pathology, clinical chemistry, hematology, gynecology, surgery, intensive care medicine, nephrology, rheumatology, and infectious diseases. We would like to express our gratitude and appreciation for all those who have stimulated, encouraged, and supported us to hold the symposium in Freiburg. This endeavor could not have been possible without the generous financial support of Asid- Bonz (Boblingen), Bayer AG (Leverkusen), Bayropharm GmbH (Koln), Baxter (Munchen), Ciba-Geigy (Wehr/Baden), Cilag GmbH (Sulzbach), Fresenius AG (Oberursel), Gambro (Martinsried), Gry-Pharma GmbH (Kirchzarten), Hoechst AG (Frankfurt), Hospal (Nurnberg), Knoll AG (Ludwigshafen), Lederle-Cyanamid (Wolfratshausen) , E. Merck (Darmstadt), MSD Sharp and Dohme GmbH (Munchen), Pfizer GmbH (Karlsruhe), and Kabi/Pfrimmer (Erlangen). We are indebted to Mrs. I. Szkibik for her invaluable ass i- stance both with the organization of the meeting and the pre- paration of the manuscripts.

This concise, clinically focused pocket handbook assembles and synthesizes the latest developments and trends in the diagnosis and treatment of CML and provides an authoritative and convenient summary of the latest progress in TKI trials, the molecular monitoring of CML responses, and the development of new therapies to overcome resistance and improve patient care. Chronic myeloid leukemia (CML) is a rare type of leukemia (1-2 per 100,000 people) but is the most common chronic myeloproliferative neoplasm. CML remains a key model for the improved understanding of the pathophysiology of a malignancy at a molecular level; CML was the first cancer to be associated with a recurring chromosome abnormality, which generates the Philadelphia (Ph) chromosome and its associated fusion gene BCR-ABL1. The clinical outcome for patients with CML has changed dramatically in the past 15 years and this has been due to the development of tyrosine kinase inhibitors (TKIs), compounds that inhibit the activity of the oncogenic BCR-ABL1 protein. A number of first-, second- and third-generation TKIs are now available for the treatment of CML, although a number of treatment challenges remain, not least the development of treatment-resistant CML. Parallel to the development of specific drugs for treating CML, major advances have been made in the field of disease monitoring and standardization of response criteria.

The extravasation of cytotoxic agents can result in severe local tissue damage and medical emergencies during tumour therapy. This revised compendium is intended to help clinicians assess any situation speedily and with certainty. The general section of the book includes topics such as predisposition, prevention, type of harm, general measures in handling extravasated drugs, specific antidotes, and documentation. In the 2nd edition, the scientific information contained in the general section and relating to the actual substances has been updated. The substance specific part of the book includes detailed instructions on handling more than 50 cytotoxic drugs, to initiate targeted measures. Templates for an extravasation set, overview tables, documentation sheets, and patient information, as we as a CD-ROM are included to support clinical practice. The book is the outcome of a consensus of an interdisciplinary working group that has collected and systematically reviewed all published literature on the topic.

Granulocyte colony-stimulating factor (G-CSF or GCSF) is a secreted glycoprotein that stimulates the proliferation and differentiation of granulocyte precursor cells, and induces mobilization of peripheral blood progenitor cells from the bone marrow. Development of recombinant human G-CSF has had a profound impact on the treatment of many diseases, including severe chronic neutropenia and cancer, and has enabled peripheral stem cell transplantation to supplant bone marrow transplantation in the autologous setting. This Milestones in Drug Therapy volume describes the experience of the last 20 years of treatment with recombinant human G-CSF, including the basic science, the use of recombinant human G-CSF in both the oncology and nononcology settings, and the safety and economics of its use. Many of the authors were the original investigators of recombinant human G-CSF and other authors are key researchers who provide their outlook for the next 20 years for use of and research with recombinant human G-CSF.

Myelodysplastic syndromes (MDS) are the most common hematological malignancies involving mostly the elderly population. The major morbidity relates to patients' symptomatic cytopenias.MDS was previously named as "preleukemia " or " smoldering leukemia" as the lack of terminal cells in MDS and because about 25% of all cases progresses into acute myeloid leukemia. According to various reports the annual incidence of MDS ranges widely from 2-12 per 100.000, increasing to 30-50 cases per 100.000 among persons aged 70 or older. It is believed that the true incidence of MDS have been underestimated however it seems to be comparable to that for multiple myeloma and chronic lymphocytic leukemia. In the past decade much progress had been made; we know more on the disease pathology, there is more emphasis on the care and more targeted therapy had been invested. Athors provide updated knowledge in this book on all clinically important aspects of the disease. Hot topics of our days are discussed in chapters by outstanding and well known scientists from all over the world. We would offer this product both for medical students and postgraduates as well as for all who are interested in this very exciting and fast progressing field of hematology. With this work authors should call attention on the disease for decision makers in healt care systems as well.