The science of blood groups was born at the beginning of this century, when the field of immunology married that of genetics. Most of the subsequent progress in immunogenetics was achieved by British investigators. The six consecutive editions of the unequaled Blood Groups in Man have long been considered as the bible of blood groupers. It is quite unfortunate that this book has not been revisited since 1975. Although one cannot do without immunogenetics, which remains useful for the identification of new blood groups and genetic studies, the focus of interest has moved somewhat today. After several decades, the molecular basis of blood groups can be investigated by biochemists. From 1950 to 1980, the ABO, Hh, and Lewis blood groups served as models and their chemical basis came to be established. The red cell membrane glycophorins carrying the MN and Ss antigens and the glycolipids with P blood group specificities were also identified and characterized. The chemical basis of the other groups, however, remained largely unknown.

This book provides a state-of-the-art description of the current status of leukodepleted blood products. Advances in technology, particularly filtration, have achieved great success in the selective removal of these white cells. This has created a new challenge - the enumeration of white cells at low concentrations in filtered products. There may be benefits of the removal of such white cells on the quality of stored red cells and platelets. Improved safety may manifest as the attenuation of febrile reactions and reduction in sensitization to HLA antigens, viral disease transmission, transfusion associated immunomodulation, transfusion-related lung injury and reperfusion injury. Since white cell removal presents logistic problems and has cost implications, a cost-benefit analysis is essential to gauge the economic benefit of this approach. All of these aspects of white cell depleted products are discussed by acknowledged experts.

th This volume comprises the Proceedings of the 15 Congress of the International Society of Forensic Haemogenetics (ISFH), held for the first time in Venezia Lido, th th Italy, on 13 -15 October 1993. The abstracts of the scientific contributions sent to the Congress have been sub divided into chapters with numbers and headings corresponding to the Congress sessions listed in the final programme. A general index of all authors, in alpha betical order, is given at the end of the book. The book consists of 188 contributions and addresses several problems presently being discussed in forensic haemogenetics. The main portion is, of course, devoted to DNA technology: present and future trends in DNA method ology, DNA polymorphisms in paternity testing and in criminal investigation, DNA sequencing, PCR methodology, quality control and quality assurance. Data have been accumulated on population genetics and biostatistics. A new look has been given at old friends, with important contributions on the molecular biology of classical markers. Conventional genetic markers have been studied. Problems connected with genetic typing and human rights have been dealt with in depth, and the history and geography of human genes have been elucidated."

In 1989, the First International Symposium on Cytokines in Hemopoiesis, Oncology, and AIDS was held in Hanover, FRG. Since then there has been an explosion of knowledge in this field. New cytokines have been discovered, on which data are presented in this book, and receptors have already been cloned for many cytokines. In clinical application, some cytokines such as TNF have almost completely left the stage, but this may not be for ever. Enormous progress has been made in the field of hemopoietic growth factors, for which clinical studies from phase I to phase III have been conducted, and some of which have even been registered for routine use. In spite of this rapid development our knowledge of how to clinically exploit the effects of cytokines is very limited and lies far behind the advances made in basic research. Even for the hemopoietic growth factors, questions regarding the effect of adjuvant therapy on survival and or on general outcome in chemother apy have still not been answered. Discussion and exchange between those involved in basic science and clinical research is still urgently needed. We hope to successfully contribute to this process by continuing the series proceedings of the International Symposia on Cytokines in Hemopoiesis, Oncology, and AIDS. Hannover, in July 1992 Mathias Freund Hartmut Link Reinhold E. Schmidt Karl Welte List of Contributors Abbadessa, V. Istituto die Clinica Medica III, Centro Interdipartimenta de Ii Ricerche in Oncologia Clinica, 90100 Palermo, Italy Abecassis, M."

This volume provides a comprehensive account of the most recent trends in human leukemia, as presented at the Ninth Wilsede Meeting. The internationally renowned contributors deal with all different aspects of these diseases: As well as discussing important clinical aspects of leukemia, new information on the biological basis of leukemia gained using the methods of molecular genetics, cell and molecular biology, virology, and immunology is covered. The book shows both the complexity of leukemia research, as well as the value of basic scientific research in furthering clinical medicine and therapy.

H. KIESEWETTER, J. KosciELNY, and F. JuNG Tbe byperoncotic colloid-osmotic pressure of tbe 10% Haes solution causes an increased intravascular volume because free tissue water flows into the vascular system [206]. Witb a volume expansion effect of about 50% an increase in intravascular volume of 750 ml (500 mi Haes and 250 mi tissue water) is expected immediately after hypervolemic hemodilution, after isovolemic bemodilution only an in crease of 250 mi ( only tissue water due to a pblebotomy of 500 mi). The blood is diluted by overloading the vascular system [245]. After isovolemic bemodilution tbe dilution effect is more marked due to the pblebotomy. Estimated by means of the total protcin concentration (Fig. 67) the dilution of plasma was 22% 1 h after isovolemic hemodilution but only 14% after bypervolemic bemodilution. Tbe plasma dilutions were almost confirmed by the concentration changes of albumin (Fig. 68). Therefore, the mixing ratio is 4. 1 to 1 (plasma to bydroxyetbyl starcb) for bypervolemic infusion of 500 ml Haes-sterillO% (200/0. 5) and 3. 7 to 1 for isovolemic dilution. Consequently, the hydroxyethyl starch concentration after isovolemic hemodilution was signifi- cantly bigher at all measuring times tban after hypervolemic hemodilution (Fig. 61). If tbe infusion was performed quickly so that no renal output of the Haes solution could ensue, a mean bydroxyetbyl starch concentration of 10. 3 g per liter plasma would be expected immediately after isovolemic hemodilution for tbe above mixing ratio, and one of 9. 0 g after hypervolemic bemodilution.

The myelodysplastic syndromes pose important clinical and scientific chal lenges which in recent years have attracted growing interest within haemato oncology and molecular genetics. Their potential as a model for the study of human leukaemogenesis makes this one of the most exciting fields in contemporary haematology. Rapid progress towards understanding these disorders had created the need for international interdisciplinary communi cation. In order to fulfil this need the First International Symposium on Myelodysplastic Syndromes was organized in Innsbruck, Austria, in June 1988. The substantial number of excellent speakers and of participants manifested the great international interest on the topic. The present volume consists of the contributions of most of the speakers at this Symposium. We wish to thank all those who submitted their manus cripts. G. ]. Mufti Franz Schmalzl Contents Classification and Cytopathology of Myelodysplastic Syndromes The Classification of Myelodysplastic Syndromes J. M. Bennett . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Classification of Myelodysplastic Syndromes in Clinical Practice: of Subtypes Frequency G. Flandrin . . . . . . . . . . . . .: . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Pathogenesis of Anaemia in the Myelodysplastic Syndrome A. Jacobs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Immunological Abnormalities in the Myelodysplastic Syndrome T. J. Hamblin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Pediatric Experiences in Myelodysplastic Syndrome H. Gadner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Myelodysplastic Syndromes in Childhood: Description of 11 Cases E. T. van't Veer-Korthof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 The Value of Cytochemical Investigations in the Diagnosis of the Myelodysplastic Syndromes F. Schmalzl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Enzyme Cytochemical Studies in Myelodysplastic Syndromes A. De Pasquale and D. Quaglino . . . . . . . . . . . . . . . . . . . . . . . . ."

Die j{hrlichen H{mophilie-Symposien befassen sich mit neuen Erkenntnissen aus der Grundlagenforschung und Klinik der H{- mophilie, verwandter angeborener und erworbener Blutungs- krankheiten und thrombophiler Diathesen. Diese Veranstaltun- gen verfolgen das Ziel, unter Mitwirkung kompetenter Modera- toren und Referenten aller involvierten Fachdisziplinen, [rzten und Wissenschaftler aus dem zentraleurop{ischen Raum aktuelle Erkenntnisse und Erfahrungen zu vermitteln und eine stetige Verbesserung der Krankenversorgung zu bewirken. Die Hauptthemen des vorliegenden Bandes sind auf therapiebe- dingte Gef{hrdungendurch Virusinfektionen und nicht-infek- ti|se Nebenwirkungen gerinnungsaktiver Plasmapr{parate ge- richtet. Im Vordergrund stehen dabei H{ufigkeit, Verlauf, Verh}tung und Therapie der HIV-Infektion, H{ufigkeit und Verh}tung der Hepatitis B- und C-Infektion sowie Behand- lungswege der Hemmk|rperh{mophilie. In weiteren Hauptthemen werden angeborene bzw. heredit{re thrombophile Diathesen, insbesondere Protein C- und Antithrombin III-Mangelzust{nde sowie neue, vor allem molekularbiologische Fortschritte in der h{mostaseologischen Diagnostik verhandelt. Den Abschlu~ bildet eine Serie freier Vortr{ge }ber spezielle klinische Probleme bei angeborenenund erworbenen H{mostasest|rungen.

Neuere Entwicklungen in der Molekulargenetik sowie die Notwendigkeit, unanfechtbare Beweise zu liefern, haben zu immer schnelleren Fortschritten auf dem Gebiet der H{mogenetik in der Gerichtsmedizin gef}hrt. Dieser Band enth{lt die Beitr{ge mit neuesten Erkenntnissen, die hierzu auf dem Kongre im September 1991 in Mainz vorgetragen wurden. Im Zentrum steht die Frage der forensischen Anwendung bzw. Andwendbarkeit der DNS-technologischen Forschung. Einige Artikel befassen sich mit Standardisierungs-, Artefakt- und Identifikationsproblemen bez}glich menschlicher ]berreste. Auch ethische und juristische Gesichtspunkte werden diskutiert.

Following the major breakthroughs in the and frequent and thorough exchange of treatment of acute leukemias in the seven- information. Hence, it was felt that a spe- ties by the introduction of intensive combi- cial series of symposia should be devoted to nation regimens, therapeutic progress has "Pharmacokinetics and Management of slowed down and the impression of stagna- Relapsed and Refractory Disease" comple- menting the established meetings on "Prog- tion may even have occured. In contrast, the knowledge about the biology of leu- nostic Factors and Treatment Strategies" kemias is rapidly expanding and allows new which will proceed in parallel. It was the insights into the pathophysiology of the aim of the international symposium disease. Further improvements also come "ACUTE LEUKEMIAS - Pharmacokine- from a better understanding of the pharma- tics and Management of Relapsed and cokinetics and pharmacodynamics of cyto- Refractory Disease" to provide an update static drugs and their mechanisms of action. of the present knowledge in this area and to Hence, novel treatment modalities can be stimulate further developments. As a sign developed on a more solid basis and ration- for the closing distance between countries al. These achievements need to be comple- and the development of effective world- mented by effective eradiation wide cooperation this symposium emerged of residual disease or its permanent control and new from the joint efforts of the German AML approaches have been derived from recent Cooperative Group and the M. D.

The clinical and experimental effects of cytokines have been realized for a long time. The clinical effects of tumor necrosis factor were noted almost 100 years ago. The basic biological effects of interferons and the hemopoietic growth factors have been known for more than 20 years. Given the basis of modern molecular biotechniques, information concern ing the mediators of cellular interactions is expanding almost exponentially. New principles in the regulation of cell growth, microenvironment, immune response, and malignancy are being discoverd right now. New therapeutic options are becoming available and have, in some areas, already crossed the threshold of clinical application. However, the way forward might be more complicated than we are in a position to recognize today. Some of the first optimistic expectations have not yet been fulfilled. Nevertheless, we are experiencing a revolution in medicine. To contribute to this process and to stimulate scientific communi in this field, we have initiated the international symposia on cytokines cation in hemopoiesis, oncology and aids. Major contributions from the first sym posium are published in this book. We thank all the authors for their contri butions, particularly those from the Hannover Medical School, who have worked hard to realize the congress and prepare these proceedings. We also thank the pharmaceutical companies whose support made this book possible. Finally we thank Professors Deicher, Poliwoda, and Riehm, heads of the Departments of Hematology and Oncology, Immunology, and Pediatric Hematology and Oncology, respectively, who encouraged us and gave us their firm support."

Since the introduction of new anthracycline derivatives and anthrachi none analogues a few years ago, aclacinomycin A (Aclarubicin) has become an established agent for the treatment of hematologic malig nancies. A special symposium was therefore held during the congress of the German Society of Hermatology and Oncology in Hannover in October 1989 to provide an up-to-date overv.iew. Leading experts from the United States, Sweden, and Germany reported on the results being obtained with aclacinomycin A, alone or combined with other agents, in patients with acute leukemias and myelodysplastic syndromes. This book is based on their contributions. As regards single-agent treatment, aclacinomycin A in myelodys plastic syndromes is dealt with, as well as its application in older patients with acute myeloid leukemia. Four contributions are devoted to the use of aclacinomycin A in combination with conventional or intermediate dose cytosine arabinoside or etoposide in patients with relapsed or refractory acute myeloid leukemia. The results reported indicate that aclacinomycin A has substantial activity in the treatment of hematologic malignancies. In summary, this book provides a valuable update on the current status of aclacinomycin A as used by experts in the treatment of he matologic malignancies."

Alex Dowsett’s pulsating autobiography lifts the lid on a decade of life in the world’s greatest pelotons and tells how he succeeded despite being the world’s only top sportsperson with haemophilia A. For over a decade Alex Dowsett had been one of Britain’s best cyclists. He has ridden Grand Tours and Classics for elite teams including Sky and Movistar and broke the iconic World Hour Record – the ultimate time trial challenge. With humour, insight and brutal honesty, Alex tells of the challenges he has faced in his struggle to reach the top and his years as a pro-cyclist. Alex has achieved all this despite being the only top sportsperson in the world with haemophilia A. He describes how the condition – in which falls can be fatal – blighted his young sporting life, and his determination to succeed in cycling. Amazingly, he went on to excel in a sport in which cuts, grazes and bruises are a given. Every professional cyclist requires courage, but Alex takes fearlessness to another level. With an allstar cycling cast, including Bradley Wiggins, Chris Froome, Lance Armstrong and Mark Cavendish, this pulsating book lifts the lid on life in the peloton at the world’s top level. Open and frank in his views, Alex recalls his highs – including his coming of age time trial victory, a famous Giro d’Italia stage victory riding solo for 18 kilometres and famously breaking the World Hour record in 2015 – as well as his frustrations at the injustices he faced in the sport. Alex announced his forthcoming retirement at the end of the 2022 season and this memoir perfectly chronicles a career in which he was driven equally by love and rage. His compelling personal story combines with his take on being part of the golden age of British cycling and his sometimes outspoken views to produce an inspirational story of sporting endeavour.

To give an update in the field of haemostasis scientists and clinicians fromoverseas and European countries met to dis- cuss the new trends in pathophysiology and clinical impli- cations. This book is devoted to the interactions of endo- thelial functions, tissue factors, coagulation inhibitors and haemostasis as well as detection and prophylaxis of thromboembolism. Data are presented of significant new re- search work on molecular and clinical approaches to diseases in haemostasis.

Acute leukemia a quite homogenous disease failed to break through the sound barriere of when untreated reveals a substantial hetero unsatisfactory cure rates even in special sub geneity in its response to therapy. While cure groups. While new protocols including more is achieved in a certain proportion of pa effective supportive care show some increase tients other cases prove to be highly resis in the initial response rates and certain im tant. The curability is superior in acute provements in the long-term results, no ben lymphoblastic (ALL) than in acute myeloid eficial effect on the relapse rate during the (AML) leukemia and - within both type- first 1 Y2 years emerged from any of these higher in children as compared to adults. regimens. Thus, high chances for cure are The two age groups and cell types can be presently restricted to children with ALL further subdivided into prognostic groups and to lesser proportions children with by special diagnostic features. Thus, in AML and adults with ALL and AML.

It is usual to associate megaloblastic anemia with folate or cobalamin deficien- cies. However, this notion, even if true in most cases, is too restricted. Megalo- blastosis in blood may also be observed in blood diseases without vitamin defi- ciency, and also after treatment with certain antineoplastic agents; in these con- ditions, the mechanisms vary with the etiology. On the other hand, folate or cobalamin deficiency may induce various clinical or biochemical disturbances without - as yet - macrocytic megaloblastic anemia. That the biochemical basis of megaloblastosis is the same in folate and cobal- amin deficiencies is due to the close metabolic interrelationships between thse two vitamins. However, the role of cobalamin deficiency in folate metabolism is still a matter of debate. Morphological abnormalities such as macrocytosis in peripheral blood and megablastosis in bone marrow, long considered to be the best indices of vitamin deficiency, are not always constant. Indeed, the improved diagnostic methods often lead to an early diagnosis of deficiency before the appearance of the usual hematological abnormalities.

The third volume of "Advances in Forensic Haemogenetics" contains the th scientific contributions presented at the 13 Congress of the International Society for Forensic Haemogenetics, held on October 19-21, 1989 in New Orleans, USA. The conference was organized and chaired by Dr. Herbert Polesky from Minneapolis. He and the local organizing committee which consisted of our friends and colleagues (J. Soubrada, L.R.Bryant, Dale D.Dykes, Ch.Harrison, P.Newall and R. Walker) deserve the thanks of our Society for a very successful meeting. Herb Polesky has also contributed a great deal to the preparation of this book. The contributions to the conference covered all fields of forensic haemo genetics, but an outstanding highlight of this conference was the application ofDNA-polymorphisms to paternity and to the identification of stains. This included basic lectures on biostatistical approaches as well as on molecular biology and many new technical approaches to our general and special aims. Forensic haemogenetics has now merged into a new discipline without having lost its original identity. On behalf of the Executive Committee of our Society I would like to extend my thanks to the authors of the articles contained in this book and to Springer-Verlag for having made such a quick publication possible. The volume should give the reader a picture of the state of the art and a survey of the most recent developments in the field of forensic and general haemo genetics.

You see things, and sa)' why? But I dream 1hings that never were, and I say, 11'hy 110t? George Bernhard Shaw Far ahead of his time, June 1st, 1909, Alexander Maximov communicated in a lecture, given in the Charite in Berlin, the fundamental knowledge, that there exists a lymphoid hemopoetic stem cell. Alexander Friedenstein explained that during the following years, Maximov also showed that the idea of interaction between hemopoetic cells and their stroma to be one of the most significant experiences. Monoclonal antibodies, recombinant DNA technics and the improvement of tissue culture models are the major developments to improve our possibilities to clarify growth and differentiation functions of hemopoetic cells. During the last two decades it was shown that soluble products, released from T cells, were not only involved in inducing B cells to produce specific immunoglobulin secretion after antigen stimulation. Furthermore, lymphokines together with other cytokines regulate the growth and differentiation of hemopoetic cells. As I have learned from Dick Gershon, our knowledge of the cellular basis for immunoregulation has come a long way since 450 B.C. Thucydides comments on the possible role of immune response in controlling the Black Death. Dick Gershon speculated that no scientific interest for these interesting observations was put forth at that time. Perhaps the problems, the Athenians were having with the Spartans, converted money from basis research into the military budget.

Publication of papers presented at the 12th International Meeting for Forensic Haemogentics Wien 1987. Topics covered included: Formal genetics, population genetics, biochemistry and serology of nearly all hereditary blood group poly- morphisms. Also several reviews of e.g. enzyme polymor- phisms; problems and aspects of the application for paternity testing; extensive articles on forensic stain information with numerous new methods and description of artifacts; polymorphisms in body fluids; quality control methods; use of biostatistics in forensic haemogentics.

For the first time, the proceedings of our biennial congress of the Society for Forensic Haemogenetics will be published by Springer-Verlag Berlin Heidelberg New York. The different areas of research now include cellu- lar allotypes, i. e. not only the traditional red cell antigens, but also those of white cells and platelets. Plasma isoproteins and intracellular isoenzy- mes, DNA polymorphisms (restriction length fragment and banding), and biostatistics are further topics in our Society. They also deserve our special attention in the future. The practical applications comprise paren- tage testing, stain analysis, population genetics, molecular biology and other immunogenetic aspects. The 11th Congress in Copenhagen was an excellent opportunity to pre- sent our broad spectrum of scientific activities at an international forum. Among the many outstanding lectures from different parts of the world, D. A. Hopkinson's contribution on genetic variation of human enzymes and H. Matsumoto's lecture on immunoglobulin allotypes in China should be mentioned here and also L. Bolund's communication on DNA. An optimal exchange of scientific information was achieved by the arrangement of main lectures, poster sessions and workshops. The Con- gress president Dr. Klavs Henningsen deserves our special thanks for his efforts in the excellent organization of this congress.

Chromosome abnormalities of cancer cells have been recognized for a long time, and have generally proven to be a highly specific marker ofmalignancy. The contri- butions collected in this book, "Tumor Aneuploidy", cover several major aspects of present knowledge conceming the occurrence and clinical significance of chromo- some abnormalities as delineated by karyotype analyses or measurements of the cellular DNA content. Certain non-random clonal chromosome losses, deletions and translocations ap- pear to represent primary genetic lesions of malignancies and reflect their clonal origin. Secondary intraneoplastic genetic evolution is suggested by major clonal ab- normalities of chromosome number and cellular DNA content. Both types of ge- netic changes have been reaching great relevance in cancer medicine, today. Although the Philadelphia chromosome was first discovered in chronic myelo- cytic leukemia (CML), by Nowell and Hungerford in 1960, new banding techniques developed in the 1970's were needed to identity this abnormality as a translocation between chromosomes 9 and 22 (t(9; 22)). Soon thereafter, further non-random translocations were detected and attributed to special diseases like t(8; 21) and t(15; 17) to acute myeloid leukemias (AML) and t(9; 22), t(4; 11), t(8; 14) to acute lymphoblastic leukemia (ALL).

Discovery and Relative Importance of Continuous Arteriovenous HemofIltration Lee W. Henderson Continuous arteriovenous hemofiltration (CAVH) has seen a brisk upswing in popularity in Europe since its introduction by Dr. Kramer and colleagues from Gottingen, West Germany in 1977 [1]. In the United States, the technique re- ceived approval as a clinical tool from the Food and Drug Administration in April 1982. This approval flowed, in no small measure, from the extensive expe- rience reported from Europe and in particular West Germany [e. g. , 2, 3]. Reports of its clinical utility now have begun to appear in the United States [4]. Removal of excess total body water using synthetic membranes in an extracor- poreal circuit dates back to the work of Alwall and the artificial kidney that he designed which permitted utilization of a hydrostatic pressure gradient to moti- vate water flow across the membrane [5]. Kolffs original rotating drum with its unencased membrane required an osmotic driving force [6]. Hemofiltration, the use of the filtration process to remove uremic solutes with the artificial kidney, in analogy with the glomerulus, was reported in 1967 [7]. This was made possible by the availability of synthetic membranes with far higher hydraulic permeability (approximately 10 times higher) than conventionally used cellulosic hemodialysis membrane. Specific applications of these "high flux" membranes to the removal primarily of excess total body water followed shortly thereafter [8].