As a clinical discipline blood transfusion encompasses enormous vista, vary ing from biotechnology to molecular biology, from plasma products, cell biology and growth factors to interleukines. Growth of knowledge in this field has been rapid, and expertise is now required to be mastered and renewed in translating these ideas for patient care. Various types of cells could be harvested - progenitor stem cells derived from bone marrow or from circulating blood as a source for transplants; in the hemostatic armoury platelets could be used prophylactically; granulocytes and mononuclear cells are available for treatment of infections or immune modulations. However, their therapeutic use carries potential complications including graft versus host disease and CMV-infection. Prevention of such complications by irradiation and by removal of immunocompetent leukocytes are important issues. Thus, production of such therapeutic materials ought to address the issues at the earliest, to eliminate those problems while adhering to the con cept of high quality; the impact of storing platelets for longer periods by using improved plastic containers or storing almost indefinitely in frozen state should be explored. Rapid progress in cell culture techniques and bio technology have enriched the transfusion medicine armoury with lympho kines, interferons and cell colony growth factors which have great potentials for enhancement of basic knowledge as well as considerable therapeutic applications in patients.

Proceedings of the Eighth Annual Symposium on Blood Transfusion, Groningen 1983, organized by the Red Cross Blood Bank Groningen-Drenthe

Human Lymphoma: The Clinical Implications of the REAL Classification is a unique volume. It is based on the recent developments in classification and overall understanding of human lymphoid neoplasms which are relatively common neoplasms and which epidemiological evidence suggests are increasing in frequency. This field has been the cause of confusion in the past as a result of conficting ideas on the classification of lymphoma and related diseases. However a new vision of the field has emerged and the is encapsulated in the pioneering REAL classification and in a forthcoming WHO scheme, both of which are covered in the book. The volume will appeal to hematologists, pathologists and oncologists and will, thanks to a diverse and expert authorship, serve to increase the working knowledge of all three groups.

Bone marrow transplantation has emerged as a major form of treatment for a broad range of human diseases. Marrow transplantation has many unique biologic features and its principles differ markedly from the transplantation of solid organs. This volume overviews the present status of bone marrow transplantation and summarizes recent progress and controversies. Ad vances in defining the underlying biology of marrow transplantation are discussed. The current status of several major clinical problem areas are reviewed, including engraftment, acute and chronic graft-versus-host dis ease, immunodeficiency, and opportunistic infections. The therapeutic role of allogeneic and autologous bone marrow transplantation is discussed, and results are compared with alternative therapies. lX List of contributors ANASETII, CLAUDIO, M. D. , Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104 APPELBAUM, FRED, M. D. , Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104 ARMITAGE, JAMES 0. , M. D. , Department of Internal Medicine, Univer sity of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, Nebraska 68105 BEATIY, PATRICK G. , M. D. , Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104 BIERMAN, PHILIP J. , M. D. , Department of Internal Medicine, Univer sity of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, Nebraska 68105 BUTTURINI, ANNA, M. D. , Department of Pediatrics, University of Parma School of Medicine, Parma, Italy CHAMPLIN, RICHARD, M. D.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology text books are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in-depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes that aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, and easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion: first, by dividing the oncology literature into specific subdivisions such as lung cancer, geni tourinary cancer, pediatric oncology, etc.; and second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

Plasma fractionation and blood transfusion are inherently linked. Blood bankers need to have a sincere interest in fractionation and purification techniques in order to understand the need for carefully controlled source material collection and initial processing. Developments point to a shift in technology, implementation and application of plasma fractions to be produced, such that early anticipation from both bloodbankers and fractionators in a joint interest and effort are needed. As usual there is good news and bad news. We are referring in that respect to the exciting presentation about the future of bloodbanking. Although the blood donor still plays a major role in bloodbanking, new technologies could terminate the conventional blood transfusion service in the next 20-40 years. Sooner or later DNA technology will play an important role in bloodbanking and bloodbankers will have to deal with cultivated red cells as a replacement of our donor blood. Several fractionation techniques like column chromatography, controlled pore glass chromatography, heparin double cold precipitation technology and polyelectrolite fractionation are available, which may result in better yields for some of the plasma proteins. These techniques are likely to replace in part the old Cohn fractionation in the near future.

The theme of this 14th International Symposium on Blood Transfusion is closely related to the work and scientific contributions of the Dutch cryobiology pioneer Dr. Herman W. Krijnen of the Dutch Red Cross Central Laboratory. Dr. Krijnen was known and respected in the national and interna tional blood transfusion community as an extremely competent scientist and a beloved and admired colleague. Dr. Krijnen was intentionally honoured with the invitation to open this symposium on cryopreservation and low temperature biology in blood transfusion and be the guest of honour at this event. Unfortunately, Dr. Krijnen suddenly died on the first of June 1989. In honour and mem ory of Dr. Krijnen this symposium will therefore be dedicated to him. Since the lOth International Symposium on Blood Transfusion in 1985 highlighted the theme of "Future developments in blood banking", major changes have occurred in the blood banking world. Most of these changes were forced upon the Blood Banks by the fear of spreading AIDS through contaminated donations. This not only led to the wide spread testing of blood, but also to a more appropriate counselling of the community and the blood donors in specific. Additionally, virus inacti vation techniques were introduced for those components derived from multiple donations and intended for a regular transfusion in haemophi lia patients and others.

The rapid and continuous upsurge of interesting data in the subject of tumor immunology necessitates the publication of an annual series to furnish the updated materials to the students, researchers, and clinicians in this rapidly advancing field. Concepts and methodologies are ever changing. Also, current research in tumor immunology promises to offer breakthroughs in the future. Important is the need to communicate to the right people the exact role of immunodiagnostic methods and immunolog ical intervention in cancer prevention and treatment. The role of immuno therapy in combination with conventional modalities of treatment needs in its proper perspective. Oncogene, interferon, lympho to be understood kines, monoclonal antibodies, natural killer cells, platelet-mediated cyto toxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell function, ab rogation of plasma-blocking factors, etc., are some of the areas that are continually advancing. Progress in these areas will have implication in cancer therapy. Further, it is already understood that if immunocompe tence of the host can be maintained at a reasonably good level, there exists the potential to increase the therapeutic indexes of conventional modalities of treatment. This series will attempt to present updated infor mation in all these areas based on contributed and solicited articles. P. K."

Since 1952, postgraduate courses for practising physicians and speci alists have been given by the Medical Faculty of the University of Leiden in the Boerhaave Quarter, in which most of its clinics and laboratories are located. During these years, recent advances in a wide variety of m dical fields and subjects have been discussed by distin guished speakers from many countries. The steadily increasing atten dance has shown that, as could be expected from the rapid progress of modern medicine, there is a widely felt need for this form of postgra duate study. In 1957, therefore, the Leiden Medical Faculty appointed a permanent committee for the organization of postgraduate medical education. Of the courses given since then, certain material proved to have sufficient immediate scientific value to justify publication, and it now gives the Committee great pleasure to announce that in collaboration with the Leiden University Press it will publish the Boerhaave Series for Postgraduate Medical Education. The first volume of this new series is the product of the course on Human Blood Coagulation given in Novem ber 1968. It is our hope that this book will prove valuable not only to those who participated in the course but also to many others working in this and associated fields."

This monograph is the first of a series which is designed to present in depth timely reviews of subjects related to the blood. Insofar as each subject lends itself, the clinical aspects of each topic will be presented as fully as is appropriate, in addition to the basic features. As a consequence, the various monographs should be found useful not solely by hematologists. Depending on the nature of each topic, it is expected that these monographs will be found important by physiologists and specialists in fields other than hematology, as well as by scientists of very diverse interests. The present treatise illus trates this point. Doctors Garby and Meldon have brought together in a most useful way the spectacular advances which have been made in the last decade or two in a field of fundamental biologic impor tance. They have also brought to the discussion of this subject their own observations and interpretations as well as their profound understanding of the respiratory functions of the blood. Maxwell M. Wintrobe Salt Lake City, Utah v Preface This volume is an attempt to summarize the present state of know ledge of the respiratory functions of blood in health and disease. Though it deals fairly thoroughly with physicochemical aspects of the blood's gas transport properties and with the molecular chemis try of hemoglobin, its main emphasis is the gas transport function of the blood in vivo and modes of its disturbance in disease."

This volume constitutes the proceedings of a satellite symposium of the XXXth congress of the International Union of Physiological Sciences. The symposium has been held In Banff, Alberta Canada July 9-11 1986. The program was organized to provide a selective overview of current developments in cardiac biophysics, biochemistry, and physiology. In order to highlight areas of develop ing ideas and to stimulate the participants' inquisitiveness into the nature and complexity of the integrated cardiovascular system, lectures and discussions were presented that emphasized evolving and sometimes provocative concepts in the field. With the same goal in mind we have, for the readers of this volume, briefly summarized the general discussions. We would like to thank several individuals whose dedication made this sym posium and publication of the proceedings possible. Mrs. Lois Kokoski and Mrs. Madeleine Aldridge of the Conference Office of the University of Calgary seemingly effortlessly handled the details of the symposium. Peter de Tombe, Dr. Peter Backx and Dr. Jeroen Bucx transcribed the general discussions. Finally, we appreciate the extra effort of our secretaries, Lenore Doell and Gregory Douglas, and the work of Anna Tyberg who prepared the final manuscripts for publication. Henk E.D.J. ter Keurs, M.D. Ph.D. John V. Tyberg, M.D. Ph.D."

Less than 50 years ago it was discovered that steady-state protein concentrations in plasma are the net result of continuous elimination and synthesis of protein molecules. The first quanti tative studies on the turnover and distribution of plasma pro teins were made around 1950, after the introduction of radio labeled protein preparations. Around 1970, another development in quantitative interpre tation of circulating proteins was initiated in clinical enzy mology. Estimation of cumulative release into plasma of cellular enzymes can be helpful in a variety of diseases to assess the extent of tissue damage and to evaluate therapy. Enzymes can be considered as biological tracers, i.e. minute quantities of protein can be accurately determined by their spe cific catalytic activities. However, radioactive tracers permit direct estimates of turnover and distr ibution by measurement of excreted radioactivity, possibilities that are not available for enzymes. Consequently, only a few techniques used in tracer studies with radiolabeled proteins can be applied to circulating tissue enzymes and this may explain the lack of communication between the fields of plasma protein metabolism and quantitative clinical enzymology. In the present study a summary is given of the basic methods used in both fields, with emphasis on the equivalence of various models and formalisms used by different authors. It is shown that major limitations in the study of circulating tissue enzymes can be overcome if two different, but simultaneously released, en zymes can be measured. The resulting method will also be applied to plasma protein metabolism."

Some three decades after bone marrow transplantation was introduced in the field of hematology and oncology, transplantation today continues to rapidly grow and expand into a variety of new modalities. Peripheral blood has been established as an effective source of autologous progenitor cells. Furthermore, the graft-versus-leukemia effect has resulted in novel strategies of adoptive immunotherapy for cancer. Finally, approaches to gene transfer and therapy are utilizing transplantation methodologies and can augment their effects. Current results, new developments and perspectives are presented in this volume. Conventional and innovative experimental approaches, the past and the future of bone marrow transplantation are reviewed and discussed by leading representatives.

This volume comes from manuscriptscontributed by invited speakers to the NATO AdvancedStudyInstitute on Biopolymers, which was held in Izmir, during August 27th - September 5th, 1984. Many more detailshave been added to the manuscripts as a resultof the interchange of ideas during the symposium. This book includes 16 papers which were originallypresented at the meeting by some of the world'sforemostinvestigators. In this volume, the existing basic knowledgeacross the wholefieldof polymericbiomaterials is reviewed.Classification, structure, composition, synthesis, modification and fabrication of these novel materialsis included in detail. Fundamental phenomena involved in the interactionof polymers with the biological environmentand resultingresponses of blood and tissue components are discussed. Modification of polymers physically, chemicallyor biochemically, in order to improve their biocompatibility is included. Selected applications of polymeric biomaterialsin Medicine, Dentistry, Biotechnology, Pharmacology and otherrelated fieldsarealsocovered. We stronglyhope thatthis book will be agreatcontribution to the rapidly expanding field of biomaterialsand willhelp to stimulate an even more excitingfuturefor th is field. ErhanPiskin AllanS. Hoffman VI ACKNOWLEDGEMENTS NATO Advanced Study Institute on "Biopolymers" was held in Izmir during August 27th - September 5th, 1984. I would like to ex press my deepest appreciation and gratitude to NATO Scientific Affairs Division, that our meeting has been accepted as a NATO ASI, and has been supported by their programmes. I wish to thank also to all the other supporting firms and organizations, especially to Hacettepe University and Turkish Scientific and Technical Research Council."

Haemoglobin is one of the most important molecules in the animal kingdom. Its function is to carry oxygen to tissues. In lower invertebrates the blood pigment is present in the haemolymph and is not bound in cells. Later in the course of phylo genesis haemoglobin remains associated with cells which produce it and in this form it reaches the peripheral circulation. In higher organisms the haemoglobin production is thus determined by two main factors: haemoglobin synthesis in erythroid cells and the formation of these erythroid cells which depends on cell proliferation in haematopoietic organs. Human haemoglobin is made up of two chains which combine from four different polypeptide chains formed in varying ratios in different periods of the life cycle. During the life span of humans the following haemoglobins are formed: embryonic haemoglobins Gower 1 and 2, foetal haemoglobin F and two adult haemoglobins A and A . E-and IX-chains are part of the embryonic haemoglobins Gower 1 (E4) and 2 Gower 2 (1X2E2). These haemoglobins predominate in embryos during the second month of pregnancy and at the end of the first trimester they are completely re placed by foetal haemoglobin F ( Y2). Adult haemoglobin A consists of two IX and two -chains and is the main component of red cells in adults. A relatively small component of red cells accounting for less than 2 % of the total haemo globin, is haemoglobin A2 (1X0)."

This symposium is devoted to Biotechnology in Blood Transfusion; there are 22 experts discussing the state of the art in the application of monoclonal anti bodies, recombinant DNA technologies and heterologous expression systems to the improvement and sometimes replacement of blood products, charac terization of blood constituents, and the effect of these developments on blood transfusion procedures. Ten and maybe five years ago the title of a symposium such as this would have been Biosciences in blood transfusion, informing what basic developments in molecular biology, biochemistry and human physiology might pertain to blood transfusion in the distant future. That future is getting closer, and not only one is interested in basic developments in immunology, recognition and identification of viral and bacterial components and products, tissue and blood bloodgroup blood group typing, typing, but also in the potential application of these developments and their economic perspectives. That is what biotechnology is all alI about: basic science telIs tells us where and how we might look for new technologies, and the development of such tech nologies is only possible if there is a perspective for improvement in quality, safety, acceptance or performance to cost ratio.

AIMS OF THE COLOGNE-SYMPOSIUM ON RADIOLABELLED PLATELETS In 1976, M. Thakur et al (1) were the first to publish a paper concerning the in vivo thrombus detection with 111- In-labelled platelets. Previous attempts at scintigraphic thrombus localisation had been disappointing because of the unspecific binding of a number of the isotopes used, as well as the poor labelling efficiency or an insufficient low gamma-emitting property. Because of its physical characteristics (2.8 days half-life, 94% gamma emission) 111 Indium turned out to be the best isotope for platelet kinetic studies as well as for the measurement of platelet incorporation by Thrombi to be used up until now. The lipophile complexes of Ill-In (8-hydroxyquinoline, acetylacetone, tropolone) diffuse passively into the platelets without altering the function or the life span of the platelets. This advantage has let to an increase in the clinical applications of 1211-In labelled platelets. Today, radiolabelled platelets are used for thrombus detection in several different medical areas such as cardiology, nephrology. angiology or neurology. Even though many scientists and hospital doctors now routinely use radiolabelled platelet as a diagnostic tool, there is as yet not a standardized labelling method. In addition to this, there are neither standardized image procedures for the different clinical applications nor an agreement about specificity and sensitivity of the method. In 1983, a symposium on Radiolabelled Cellular Blood Elements was organized by M.Thakur, M.R.Hardeman and M.D.

During the past decade, there have been numerous direct and indirect scientific contributions to both the etiology and therapy of aplastic anemia and related bone marrow failure syndromes. Clinical observations, such as autologous bone marrow recovery after conditioning with immunosup pressive agents for bone marrow transplantation; failure to achieve en graftment in some identical twins without prior immunosuppressive ther apy; and hematologic response to immunosuppressive agents, have led to the concept of immune-mediated etiology of acquired aplastic anemia. Such a concept was further strengthened by laboratory findings, implicat ing the role of activated cytotoxic T lymphocytes and abnormal produc tion of inhibitory lymphokines. The immunologic mechanisms may also apply to the idiosyncratic bone marrow aplasias associated with drugs, toxic chemicals, and viruses. These agents may alter normal cellular recog nition sites by interacting with cellular components and result in loss of self tolerance. Immunologic mechanisms have long been advocated in many other organ failures, and the hemopoietic organ is no exception. It is of interest that parallel clinical and laboratory investigations in juvenile diabetes mellitus type I and in rodent models of this disease have yielded results compatible with the same pathogenic mechanisms. The infiltration of pancreatic islets by activated T lymphocytes, functional and morphological alterations of islet cells upon incubation with lymphokines such as gamma interferon and tumor necrosis factor, and clinical response to cyclosporine are a few examples."

An up-to-date overview of blood coagulation, hemostatis, and thrombosis, this volume also provides a state-of-the-art report of current anti-thrombotic and anti-coagulant strategies as well as a summary of current research interest in the area and potential future targets. It attempts to balance traditional pharmacology with the newer sciences of molecular biology and in so doing, sets a framework for future advances in the field. The book is a concise, current and useful reference for the basic researcher as well as the practicing physician working in the fields of cardiology, internal medicine or surgery.

This volume documents our growing understanding of the human major histocompatibility complex. The application of this information is ever more important as the limits of transplantation continue to be reduced, including the recent success of bone marrow transplantation between unrelated but closely matched individuals. In addition, the need to transfuse platelets in the face of immunologic barriers continues to challenge transfusion services. Thus, the serologic information summarized in this volume is essential for optimal patient care. At the same time, recombinant DNA technology has led to a revolution in our understanding of many aspects of basic biology. Among the advances has been the initial characterization of the structure of some HLA loci. While this will ultimately improve clinical services, constant reference to serologic data is essential so that the powerful new techniques can be applied in the most effective ways. The timing of the First Red Cross International Histocompatibility Workshop is fortunate as it brings together experts from around the world to address the state of the art. We are all grateful to Dr. John Lee and his colleagues for organizing the workshop, and for bringing together in this volume the material to be presented in Beijing during October 17-23, 1990. Leon W. Hoyer, M.D.

In 1628 William Harvey published his discovery of the existence of the microcirculation which he deduced from careful anatomical and physiological study. Thirty-three years later, Malpighi confirmed the presence of capillaries through direct microscopical observation. Subsequent scientific advance has been slow, and in view of the fact that microvascular in the genesis and expression of many pathophysiology may be implicated diseases, our know ledge of human microvascular function is surprisingly limited. This ignorance attests to the difficulty of studying something that is both minute and inaccessible without disturbing the quantity that is being measured. In the last fifteen years, however, direct techniques have been developed for studying human microvascular pressure, flow and permeability. These methods have provided new insights into human microvascular function in health and disease. At the same time there has been a steady growth of new indirect techniques based on a w ide range of physical principles that reflect some or other aspect of microvascular function.

Proceedings of the Tenth Annual Symposium on Blood Transfusion, Groningen 1985, organized by the Red Cross Blood Bank Groningen-Drenthe

The continuous advances in our understanding of hematology and neo plastic disorders have made possible this third volume of reviews. Their purpose is to summarize investigations which have defined new concepts, and, it is hoped, stimulate new ideas. In the choice of subjects, we have attempted to retain the balance between academic and clinical interests. We are grateful to the contributors, who have maintained the high stan dards set in the earlier volumes, and for feedback from readers. Both have helped to orient the direction of this series. It was a reader who pointed out that the title of the two earlier volumes, The Year in Hematol ogy, was misleading since it suggested a detailed review of trends and findings limited to the last year. In response to this valid comment, The Year . . . has been changed to Contemporary . . . and the scope has been expanded to encompass the kindred disciplines of hematology and oncol ogy. Another editor, Franco M. Muggia, has been added to provide addi tional expertise for the latter field. The title of the present and future volumes has been changed to Contemporary Hematology/Oncology. It has been pointed out to us that considerable ingenuity will be needed to find topics not already covered. We believe that the papers in the present volume have met this challenge. As before, the readers' comments con cerning Contemporary Hematology/Oncology will be appreciated. Joseph LoBue Albert S. Gordon Robert Silber Franco M."

This volume reports the proceedings of a NATO Advanced Workshop held at Cameron House Hotel, Loch Lomond, Scotland, from May 2 - 5, 1994. The major impetus for this workshop was the realisation, over the past 7 years, that the Epstein-Barr virus is associated with a proportion of cases of Hodgkin's disease and is likely to play an aetiological role. There were four main aims of the workshop: first, to discuss the recent findings in relation to Epstein Barr virus and the aetiology of Hodgkin's disease; second, to relate these data to the epidemiology of Hodgkin's disease; third, to discuss other potential aetiological factors and finally, to discuss future directions for research into Hodgkin's disease. Leading experts in the field have contributed chapters to this volume. There is some overlap among chapters, particularly regarding Epstein-Barr virus, thereby allowing different groups to express views on similar topics. Perhaps, however, the most surprising feature of the workshop was the lack of controversy regarding the role of Epstein-Barr virus in Hodgkin's disease, an association that was treated with great scepticism at the beginning of the decade. The first three chapters, by Alexander, Taylor et al., and Levine el al., discuss the epidemiology of Hodgkin's disease with particular attention to clustering and genetic susceptibility. These chapters represent the first attempt to bring together epidemiological and molecular studies in Hodgkin's disease.